George Somero

All Publications

• From molecules to morphology: How food supply influences the larvae of sea urchins across all levels of biological organization. Molecular ecology Somero, G. N. 2024: e17384

  Abstract

  An important goal of many studies in molecular ecology is to utilize molecular tools to elucidate how critical traits like metabolism and growth are affected by environmental stressors and how organisms offset these stresses by adaptive molecular-level responses. Stress from food deprivation may be critical for early developmental stages that require a continued supply of substrates for energy metabolism and growth if development is to be completed. In a 'From the Cover' article in this issue of Molecular Ecology, Li et al. (2023) examined the effects of withholding food (unicellular algae) on 10 traits of larvae of the purple sea urchin (Strongylocentrotus purpuratus), ranging from the molecular level (gene expression) to morphology. Overall, this study sheds new light on the plasticity of larval development and the tight linkages that exist among traits as they respond to changes in food availability. Importantly, shifts in the sources of food utilized under different dietary treatments show the plasticity of these larvae to alter reliance on endogenous energy stores and dissolved organic matter (DOM) as algae deprivation continues. The effects of global change on the amounts and phenology of productivity in the seas make this type of integrated, multi-level analysis an important tool for predicting the future states of marine ecosystems.

  View details for DOI 10.1111/mec.17384

  View details for PubMedID 38757458

• Tissue-specific temperature dependence of RNA editing levels in zebrafish. BMC biology Li, W., Bu, M., Hu, R., Jiang, S., Chen, L., Somero, G. N. 2023; 21 (1): 262

  Abstract

  RNA editing by adenosine deaminase acting on RNA (ADAR) occurs in all metazoans and fulfils several functions. Here, we examined effects of acclimation temperature (27 °C, 18 °C,13 °C) on editing patterns in six tissues of zebrafish (Danio rerio).Sites and total amounts of editing differed among tissues. Brain showed the highest levels, followed by gill and skin. In these highly edited tissues, decreases in temperatures led to large increases in total amounts of editing and changes in specific edited sites. Gene ontology analysis showed both similarities (e.g., endoplasmic reticulum stress response) and differences in editing among tissues. The majority of edited sites were in transcripts of transposable elements and the 3'UTR regions of protein coding genes. By experimental validation, translation efficiency was directly related to extent of editing of the 3'UTR region of an mRNA.RNA editing increases 3'UTR polymorphism and affects efficiency of translation. Such editing may lead to temperature-adaptive changes in the proteome through altering relative amounts of synthesis of different proteins.

  View details for DOI 10.1186/s12915-023-01738-4

  View details for PubMedID 37981664

  View details for PubMedCentralID PMC10659053

• Oxidative stress effects are not correlated with differences in heat tolerance among congeners of Mytilus. The Journal of experimental biology Dowd, W. W., Somero, G. N. 2023

  Abstract

  The physiological mechanisms that limit thermal tolerance are broadly relevant to comparative biology and global change. Species differences in macromolecular stability play important roles in evolved patterns of heat tolerance, but other mechanisms such as oxidative stress have also been hypothesized to contribute. For example, mussels in the genus Mytilus exhibit evolved physiological differences at several levels of organization that have been linked with interspecific differences in whole-organism heat tolerance. Both omics and behavioral studies suggested that variation in resistance to oxidative stress plays a role in these differences. Functional data are needed to test this hypothesis. Here, we compared three Mytilus congeners to examine whether susceptibility to oxidative stress contributes to acute heat tolerance. We assayed activities of two antioxidant enzymes (catalase, superoxide dismutase), as well as levels of oxidative damage to lipids, DNA, and individual proteins (using gel-based proteomics methods). In addition, we assessed these oxidative stress responses after repeated episodes of heat stress experienced in air or while immersed in seawater, given that survival and competitive outcomes between Mytilus congeners differ in these two contexts. The results are generally inconsistent with patterns that would be expected if oxidative stress contributes to thermal sensitivity. Rather, the more heat-tolerant congeners suffer comparable or even elevated levels of oxidative damage. As predicted, different treatment contexts led to distinct changes in proteome-wide abundance patterns and, to a lesser extent, protein carbonylation profiles. Overall, the results question the relevance of oxidative damage as a mediator of heat tolerance in this genus.

  View details for DOI 10.1242/jeb.246033

  View details for PubMedID 37416965

• Turning a page: remaining a top competitor in an evolving publication ecosystem. The Journal of experimental biology Somero, G. N. 2023; 226 (2)

  Abstract

  Journal of Experimental Biology (JEB) is celebrating its first 100 years this year. My own relationship with the journal spans over six decades and encompasses a variety of roles: reader, author, Editor (1995-2000), Editorial Advisory Board member (2000 to present) and Director on the board of its publisher, The Company of Biologists (2003-2009). I was therefore delighted when the journal Editors asked me to write a Perspective to reflect on how the journal and the publishing environment in which it competes have evolved over this long period, and to peek into my crystal ball and comment on what the future might hold for the journal and the primary fields it covers: comparative-environmental-evolutionary physiology, neuroethology and biomechanics.

  View details for DOI 10.1242/jeb.245153

  View details for PubMedID 36637438

• Solutions: how adaptive changes in cellular fluids enable marine life to cope with abiotic stressors MARINE LIFE SCIENCE & TECHNOLOGY Somero, G. N. 2022

  View details for DOI 10.1007/s42995-022-00140-3

  View details for Web of Science ID 000841050000001

• Solutions: how adaptive changes in cellular fluids enable marine life to cope with abiotic stressors. Marine life science & technology Somero, G. N. 2022; 4 (3): 389-413

  Abstract

  The seas confront organisms with a suite of abiotic stressors that pose challenges for physiological activity. Variations in temperature, hydrostatic pressure, and salinity have potential to disrupt structures, and functions of all molecular systems on which life depends. During evolution, sequences of nucleic acids and proteins are adaptively modified to "fit" these macromolecules for function under the particular abiotic conditions of the habitat. Complementing these macromolecular adaptations are alterations in compositions of solutions that bathe macromolecules and affect stabilities of their higher order structures. A primary result of these "micromolecular" adaptations is preservation of optimal balances between conformational rigidity and flexibility of macromolecules. Micromolecular adaptations involve several families of organic osmolytes, with varying effects on macromolecular stability. A given type of osmolyte generally has similar effects on DNA, RNA, proteins and membranes; thus, adaptive regulation of cellular osmolyte pools has a global effect on macromolecules. These effects are mediated largely through influences of osmolytes and macromolecules on water structure and activity. Acclimatory micromolecular responses are often critical in enabling organisms to cope with environmental changes during their lifetimes, for example, during vertical migration in the water column. A species' breadth of environmental tolerance may depend on how effectively it can vary the osmolyte composition of its cellular fluids in the face of stress. Micromolecular adaptations remain an under-appreciated aspect of evolution and acclimatization. Further study can lead to a better understanding of determinants of environmental tolerance ranges and to biotechnological advances in designing improved stabilizers for biological materials.

  View details for DOI 10.1007/s42995-022-00140-3

  View details for PubMedID 37073170

  View details for PubMedCentralID PMC10077225

• Effects of heat acclimation on cardiac function in the intertidal mussel Mytilus californianus: can laboratory-based indices predict survival in the field? The Journal of experimental biology Moyen, N. E., Somero, G. N., Denny, M. W. 2022

  Abstract

  Thermal performance curves are commonly used to investigate effects of heat acclimation on thermal tolerance and physiological performance. However, recent work indicates that metrics of these curves heavily depend on experimental design and may be poor predictors of animals' survival during heat events in the field. In intertidal mussels, cardiac thermal performance (CTP) tests have been widely used as indicators of animals' acclimation or acclimatization state, providing two indices of thermal responses: critical temperature (Tcrit; the temperature above which heart rate abruptly declines) and flatline temperature (Tflat; the temperature where heart rate ceases). Despite wide use of CTP tests, it remains largely unknown how Tcrit and Tflat change within a single individual after heat acclimation, and whether changes in these indices can predict altered survival in the field. Here, we address these issues by evaluating changes in CTP indices in the same individuals before and after heat acclimation. For control mussels, merely reaching Tcrit was not lethal, whereas remaining at Tcrit for ≥10 min was lethal. Heat acclimation significantly increased Tcrit only in mussels with an initially low Tcrit (<35°C), but improved mussels' survival time above Tcrit by 20 min on average. Tflat increased by 1.6°C with heat acclimation, but it is unlikely that increased Tflat improves survival in the field. In summary, Tcrit and Tflatper se may fall short of providing quantitative indices of thermal tolerance in mussels; instead, a combination of Tcrit and tolerance time at temperatures ≥Tcrit better define changes in thermal tolerance with heat acclimation.

  View details for DOI 10.1242/jeb.243050

  View details for PubMedID 35388895

• Thermal adaptation of mRNA secondary structure: stability versus lability. Proceedings of the National Academy of Sciences of the United States of America Liao, M., Dong, Y., Somero, G. N. 2021; 118 (45)

  Abstract

  Macromolecular function commonly involves rapidly reversible alterations in three-dimensional structure (conformation). To allow these essential conformational changes, macromolecules must possess higher order structures that are appropriately balanced between rigidity and flexibility. Because of the low stabilization free energies (marginal stabilities) of macromolecule conformations, temperature changes have strong effects on conformation and, thereby, on function. As is well known for proteins, during evolution, temperature-adaptive changes in sequence foster retention of optimal marginal stability at a species' normal physiological temperatures. Here, we extend this type of analysis to messenger RNAs (mRNAs), a class of macromolecules for which the stability-lability balance has not been elucidated. We employ in silico methods to determine secondary structures and estimate changes in free energy of folding (DeltaGfold) for 25 orthologous mRNAs that encode the enzyme cytosolic malate dehydrogenase in marine mollusks with adaptation temperatures spanning an almost 60°C range. The change in free energy that occurs during formation of the ensemble of mRNA secondary structures is significantly correlated with adaptation temperature: DeltaGfold values are all negative and their absolute values increase with adaptation temperature. A principal mechanism underlying these adaptations is a significant increase in synonymous guanine + cytosine substitutions with increasing temperature. These findings open up an avenue of exploration in molecular evolution and raise interesting questions about the interaction between temperature-adaptive changes in mRNA sequence and in the proteins they encode.

  View details for DOI 10.1073/pnas.2113324118

  View details for PubMedID 34728561

• An integrated, multi-level analysis of thermal effects on intertidal molluscs for understanding species distribution patterns. Biological reviews of the Cambridge Philosophical Society Dong, Y., Liao, M., Han, G., Somero, G. N. 2021

  Abstract

  Elucidating the physiological mechanisms that underlie thermal stress and discovering how species differ in capacities for phenotypic acclimatization and evolutionary adaptation to this stress is critical for understanding current latitudinal and vertical distribution patterns of species and for predicting their future state in a warming world. Such mechanistic analyses require careful choice of study systems (species and temperature-sensitive traits) and design of laboratory experiments that reflect the complexities of in situ conditions. Here, we critically review a wide range of studies of intertidal molluscs that provide mechanistic accounts of thermal effects across all levels of biological organization - behavioural, organismal, organ level, cellular, molecular, and genomic - and show how temperature-sensitive traits govern distribution patterns and capacities for coping with thermal stress. Comparisons of congeners from different thermal habitats are especially effective means for identifying adaptive variation. We employ these mechanistic analyses to illustrate how species differ in the severity of threats posed by rising temperature. Counterintuitively, we show that some of the most heat-tolerant species may be most threatened by increases in temperatures because of their small thermal safety margins and minimal abilities to acclimatize to higher temperatures. We discuss recent molecular biological and genomic studies that provide critical foundations for understanding the types of evolutionary changes in protein structure, RNA secondary structure, genome content, and gene expression capacities that underlie adaptation to temperature. Duplication of stress-related genes, as found in heat-tolerant molluscs, may provide enhanced capacity for coping with higher temperatures. We propose that the anatomical, behavioural, physiological, and genomic diversity found among intertidal molluscs, which commonly are of critical importance and high abundance in these ecosystems, makes this group of animals a highly appropriate study system for addressing questions about the mechanistic determinants of current and future distribution patterns of intertidal organisms.

  View details for DOI 10.1111/brv.12811

  View details for PubMedID 34713568

• A tribute to Dr. Serge N. Timasheff, our mentor. Biophysical reviews Aune, K., Lee, J., Prakash, V., Bhat, R., Andreu, J., Monasterio, O., Perez-Ramirez, B., Shearwin, K., Arakawa, T., Carpenter, J., Crowe, J., Crowe, L., Somero, G., Gagnon, P., Charles, M. T. 2021; 13 (4): 459-484

  Abstract

  Dr. Serge N. Timasheff, our mentor and friend, passed away in 2019. This article is a collection of tributes from his postdoctoral fellows, friends, and daughter, who all have been associated with or influenced by him or his research. Dr. Timasheff is a pioneer of research on thermodynamic linkage between ligand interaction and macromolecular reaction. We all learned a great deal from Dr. Timasheff, not only about science but also about life.

  View details for DOI 10.1007/s12551-021-00814-9

  View details for PubMedID 34471434

• The Goldilocks Principle: A Unifying Perspective on Biochemical Adaptation to Abiotic Stressors in the Sea. Annual review of marine science Somero, G. N. 2021

  Abstract

  The ability of marine organisms to thrive over wide ranges of environmental stressors that perturb structures of proteins, nucleic acids, and lipids illustrates the effectiveness of adaptation at the biochemical level. A critical role of these adaptations is to achieve a proper balance between structural rigidity, which is necessary for maintaining three-dimensional conformation, and flexibility, which is required to allow changes in conformation during function. The Goldilocks principle refers to this balancing act, wherein structural stability and functional properties are poised at values that are just right for the environment the organism faces. Achieving this balance involves changes in macromolecular sequence and adaptive change in the composition of the aqueous or lipid milieu in which macromolecules function. This article traces the development of the field of biochemical adaptation throughout my career and shows how comparative studies of marine animals from diverse habitats have shed light on fundamental properties of life common to all organisms. Expected final online publication date for the Annual Review of Marine Science, Volume 14 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  View details for DOI 10.1146/annurev-marine-022521-102228

  View details for PubMedID 34102065

• Introduction to the special issue: Comparative biology of cellular stress responses in animals. Journal of experimental zoology. Part A, Ecological and integrative physiology Kultz, D., Somero, G. N. 2020

  View details for DOI 10.1002/jez.2395

  View details for PubMedID 32588555

• Mussels' acclimatization to high, variable temperatures is lost slowly upon transfer to benign conditions. The Journal of experimental biology Moyen, N. E., Somero, G. N., Denny, M. W. 2020

  Abstract

  Climate change is increasing the temperature variability animals face, and thermal acclimatization allows animals to adjust adaptively to this variability. While the rate of heat-acclimatization has received some study, little is known about how long these adaptive changes remain without continuing exposure to heat stress. This study explored the rate at which field-acclimatization states are lost when temperature variability is minimized during constant submersion. California mussels (Mytilus californianus) with different acclimatization states were collected from high- and low-zone sites (12°C vs. 5°C daily temperature ranges, respectively) and then kept submerged at 15°C for eight weeks. Each week, mussels' cardiac thermal performance was measured as a metric of acclimatization state; critical (T crit) and flatline (FLT) temperatures were recorded. Across eight weeks of constant submersion high-zone mussels' mean T crit decreased by 1.07°C from baseline, but low-zone mussels' mean T crit was unchanged. High- and low-zone mussels' mean maximum heart rate (HR) and resting HR decreased 12% and 35%, respectively. FLT was unchanged in both groups. These data suggest that T crit and HR are more physiologically plastic in response to the narrowing of an animal's daily temperature range than is FLT, and that an animal's prior acclimatization state (high vs. low) influences the acclimatory capacity of T crit Approximately two months were required for the high-zone mussels' cardiac thermal performance to reach that of the low-zone mussels, suggesting that acclimatization to high and variable temperatures may persist long enough to enable these animals to cope with intermittent bouts of heat stress.

  View details for DOI 10.1242/jeb.222893

  View details for PubMedID 32457061

• Establishing typical values for hemocyte mortality in individual mussels (<it>Mytilus</it> <it>californianus</it>) using fluorescence-activated cell sorting Moyen, N., Bump, P., Somero, G., Denny, M. WILEY. 2020

  View details for DOI 10.1096/fasebj.2020.34.s1.01786

  View details for Web of Science ID 000546107902338

• A single heat-stress bout induces rapid and prolonged heat acclimation in the California mussel, Mytilus californianus. Proceedings. Biological sciences Moyen, N. E., Crane, R. L., Somero, G. N., Denny, M. W. 2020; 287 (1940): 20202561

  Abstract

  Climate change is not only causing steady increases in average global temperatures but also increasing the frequency with which extreme heating events occur. These extreme events may be pivotal in determining the ability of organisms to persist in their current habitats. Thus, it is important to understand how quickly an organism's heat tolerance can be gained and lost relative to the frequency with which extreme heating events occur in the field. We show that the California mussel, Mytilus californianus-a sessile intertidal species that experiences extreme temperature fluctuations and cannot behaviourally thermoregulate-can quickly (in 24-48 h) acquire improved heat tolerance after exposure to a single sublethal heat-stress bout (2 h at 30 or 35°C) and then maintain this improved tolerance for up to three weeks without further exposure to elevated temperatures. This adaptive response improved survival rates by approximately 75% under extreme heat-stress bouts (2 h at 40°C). To interpret these laboratory findings in an ecological context, we evaluated 4 years of mussel body temperatures recorded in the field. The majority (approx. 64%) of consecutive heat-stress bouts were separated by 24-48 h, but several consecutive heat bouts were separated by as much as 22 days. Thus, the ability of M. californianus to maintain improved heat tolerance for up to three weeks after a single sublethal heat-stress bout significantly improves their probability of survival, as approximately 33% of consecutive heat events are separated by 3-22 days. As a sessile animal, mussels likely evolved the capability to rapidly gain and slowly lose heat tolerance to survive the intermittent, and often unpredictable, heat events in the intertidal zone. This adaptive strategy will likely prove beneficial under the extreme heat events predicted with climate change.

  View details for DOI 10.1098/rspb.2020.2561

  View details for PubMedID 33290677

• Mussels' acclimatization to high, variable temperatures is lost slowly upon transfer to benign conditions. The Journal of experimental biology Moyen, N. E., Somero, G. N., Denny, M. W. 2020

  Abstract

  Climate change is increasing the temperature variability animals face, and thermal acclimatization allows animals to adjust adaptively to this variability. While the rate of heat-acclimatization has received some study, little is known about how long these adaptive changes remain without continuing exposure to heat stress. This study explored the rate at which field-acclimatization states are lost when temperature variability is minimized during constant submersion. California mussels (Mytilus californianus) with different acclimatization states were collected from high- and low-zone sites (∼12°C vs. ∼5°C daily temperature ranges, respectively) and then kept submerged at 15°C for eight weeks. Each week, mussels' cardiac thermal performance was measured as a metric of acclimatization state; critical (Tcrit) and flatline (FLT) temperatures were recorded. Across eight weeks of constant submersion high-zone mussels' mean Tcrit decreased by 1.07°C from baseline, but low-zone mussels' mean Tcrit was unchanged. High- and low-zone mussels' mean maximum heart rate (HR) and resting HR decreased ∼12% and 35%, respectively. FLT was unchanged in both groups. These data suggest that Tcrit and HR are more physiologically plastic in response to the narrowing of an animal's daily temperature range than is FLT, and that an animal's prior acclimatization state (high vs. low) influences the acclimatory capacity of Tcrit. Approximately two months were required for the high-zone mussels' cardiac thermal performance to reach that of the low-zone mussels, suggesting that acclimatization to high and variable temperatures may persist long enough to enable these animals to cope with intermittent bouts of heat stress.

  View details for DOI 10.1242/jeb.222893

  View details for PubMedID 34005552

• Establishing typical values for hemocyte mortality in individual California mussels, Mytilus californianus. Fish & shellfish immunology Moyen, N. E., Bump, P. A., Somero, G. N., Denny, M. W. 2020

  Abstract

  Hemocytes are immune cells in the hemolymph of invertebrates that play multiple roles in response to stressors; hemocyte mortality can thus serve as an indicator of overall animal health. However, previous research has often analyzed hemolymph samples pooled from several individuals, which precludes tracking individual responses to stressors over time. The ability to track individuals is important, however, because large inter-individual variation in response to stressors can confound the interpretation of pooled samples. Here, we describe protocols for analysis of inter- and intra-individual variability in hemocyte mortality across repeated hemolymph samples of California mussels, Mytilus californianus, free from typical abiotic stressors. To assess individual variability in hemocyte mortality with serial sampling, we created four groups of 15 mussels each that were repeatedly sampled four times: at baseline (time zero) and three subsequent times separated by either 24, 48, 72, or 168 h. Hemocyte mortality was assessed by fluorescence-activated cell sorting (FACS) of cells stained with propidium iodide. Our study demonstrates that hemolymph can be repeatedly sampled from individual mussels without mortality; however, there is substantial inter- and intra-individual variability in hemocyte mortality through time that is partially dependent on the sampling interval. Across repeated samples, individual mussels' hemocyte mortality had, on average, a range of ∼6% and a standard deviation of ∼3%, which was minimized with sampling periods ≥72 h apart. Due to this intra-individual variability, obtaining ≥2 samples from a specimen will more accurately establish an individual's baseline. Pooled-sample means were similar to individual-sample means; however, pooled samples masked the individual variation in each group. Overall, these data lay the foundation for future work exploring individual mussels' temporal responses to various stressors on a cellular level.

  View details for DOI 10.1016/j.fsi.2020.02.069

  View details for PubMedID 32135339

• The cellular stress response and temperature: Function, regulation, and evolution. Journal of experimental zoology. Part A, Ecological and integrative physiology Somero, G. N. 2020

  Abstract

  The cellular stress response (CSR) is critical for enabling organisms to cope with thermal damage to proteins, nucleic acids, and membranes. It is a graded response whose properties vary with the degree of cellular damage. Molecular damage has positive, as well as negative, function-perturbing effects. Positive effects include crucial regulatory interactions that orchestrate involvement of the different components of the CSR. Thermally unfolded proteins signal for rapid initiation of transcription of genes encoding heat shock proteins (HSPs), central elements of the heat shock response (HSR). Thermal disruption of messenger RNA (mRNA) secondary structures in untranslated regions leads to the culling of the mRNA pool: thermally labile mRNAs for housekeeping proteins are degraded by exonucleases; heat-resistant mRNAs for stress proteins like HSPs then can monopolize the translational apparatus. Thus, proteins and RNA function as "cellular thermometers," and evolved differences in their thermal stabilities enable rapid initiation of the CSR whenever cell temperature rises significantly above the normal thermal range of a species. Covalent DNA damage, which may result from increased production of reactive oxygen species, is temperature-dependent; its extent may determine cellular survival. High levels of stress that exceed capacities for molecular repair can lead to proteolysis, inhibition of cell division, and programmed cell death (apoptosis). Onset of these processes may occur later in the stress period, after initiation of the HSR, to allow HSPs opportunity to restore protein homeostasis. Delay of these energy costly processes may also result from shortfalls in availability of adenosine triphosphate and reducing power during times of peak stress.

  View details for DOI 10.1002/jez.2344

  View details for PubMedID 31944627

• PRESENT AND FUTURE ADAPTATION OF MARINE SPECIES ASSEMBLAGES DNA-Based Insights into Climate Change from Studies of Physiology, Genomics, and Evolution OCEANOGRAPHY Palumbi, S. R., Evans, T. G., Pespeni, M. H., Somero, G. N. 2019; 32 (3): 82–93

  View details for DOI 10.5670/oceanog.2019.314

  View details for Web of Science ID 000484602000012

• PISCO ADVANCES MADE THROUGH THE FORMATION OF A LARGE-SCALE, LONG-TERM CONSORTIUM FOR INTEGRATED UNDERSTANDING OF COASTAL ECOSYSTEM DYNAMICS OCEANOGRAPHY Menge, B. A., Milligan, K., Caselle, J. E., Barth, J. A., Blanchette, C. A., Carr, M. H., Chan, F., Cowen, R. K., Denny, M., Gaines, S. D., Hofmann, G. E., Kroeker, K. J., Lubchenco, J., McManus, M. A., Novak, M., Paiumbi, S. R., Raimondi, P. T., Somero, G. N., Warner, R. R., Washburn, L., White, J. 2019; 32 (3): 16–25

  View details for DOI 10.5670/oceanog.2019.307

  View details for Web of Science ID 000484602000005

• Impact of heating rate on cardiac thermal tolerance in the California mussel, Mytilus californianus. The Journal of experimental biology Moyen, N. E., Somero, G. N., Denny, M. W. 2019

  Abstract

  Intertidal communities of wave-swept rocky shores have served as a powerful model system for experiments in ecology, and mussels (the dominant competitor for space in the mid-intertidal zone) play a central role in determining community structure in this physically stressful habitat. Consequently, our ability to account for mussels' physiological responses to thermal stress affects ecologists' abilities to predict the impacts of a warming climate on this ecosystem. Here, we examine the effect of heating rate on cardiac thermal tolerance in the ribbed mussel, Mytilus californianus, comparing populations from high and low sites in the intertidal zone where emersion duration leads to different mean daily heating rates. Two temperature-related cardiac variables were examined: 1) the critical temperature (Hcrit) at which heart rate (HR) precipitously declines, and 2) flatline temperature (FLT) where HR reaches zero. Mussels were heated in air at slow, moderate, and fast rates, and heart rate was measured via an infrared sensor affixed to the shell. Faster heating rates significantly increased Hcrit in high-, but not low-zone mussels, and Hcrit was higher in high vs. - mussels, especially at the fastest heating rate. By contrast, FLT did not differ between zones, and was minimally affected by heating rate. Since heating rate significantly impacted high- but not low-zone mussels' cardiac thermal tolerance, realistic zone-specific heating rates must be used in laboratory tests if those tests are to provide accurate information for ecological models attempting to predict the effects of increasing temperature on intertidal communities.

  View details for DOI 10.1242/jeb.203166

  View details for PubMedID 31395674

• Comparing mutagenesis and simulations as tools for identifying functionally important sequence changes for protein thermal adaptation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Liao, M., Somero, G. N., Dong, Y. 2019; 116 (2): 679–88

  View details for DOI 10.1073/pnas.1817455116

  View details for Web of Science ID 000455086900050

• Comparing mutagenesis and simulations as tools for identifying functionally important sequence changes for protein thermal adaptation. Proceedings of the National Academy of Sciences of the United States of America Liao, M., Somero, G. N., Dong, Y. 2018

  Abstract

  Comparative studies of orthologous proteins of species evolved at different temperatures have revealed consistent patterns of temperature-related variation in thermal stabilities of structure and function. However, the precise mechanisms by which interspecific variations in sequence foster these adaptive changes remain largely unknown. Here, we compare orthologs of cytosolic malate dehydrogenase (cMDH) from marine molluscs adapted to temperatures ranging from -1.9 °C (Antarctica) to 55 °C (South China coast) and show how amino acid usage in different regions of the enzyme (surface, intermediate depth, and protein core) varies with adaptation temperature. This eukaryotic enzyme follows some but not all of the rules established in comparisons of archaeal and bacterial proteins. To link the effects of specific amino acid substitutions with adaptive variations in enzyme thermal stability, we combined site-directed mutagenesis (SDM) and in vitro protein experimentation with in silico mutagenesis using molecular dynamics simulation (MDS) techniques. SDM and MDS methods generally but not invariably yielded common effects on protein stability. MDS analysis is shown to provide insights into how specific amino acid substitutions affect the conformational flexibilities of mobile regions (MRs) of the enzyme that are essential for binding and catalysis. Whereas these substitutions invariably lie outside of the MRs, they effectively transmit their flexibility-modulating effects to the MRs through linked interactions among surface residues. This discovery illustrates that regions of the protein surface lying outside of the site of catalysis can help establish an enzyme's thermal responses and foster evolutionary adaptation of function.

  View details for PubMedID 30584112

• RNA thermosensors: how might animals exploit their regulatory potential? The Journal of experimental biology Somero, G. N. 2018; 221 (Pt 4)

  Abstract

  The secondary and tertiary orders of RNA structure are crucial for a suite of RNA-related functions, including regulation of translation, gene expression and RNA turnover. The temperature sensitivity of RNA secondary and tertiary structures is exploited by bacteria to fabricate RNA thermosensing systems that allow a rapid adaptive response to temperature change. RNA thermometers (RNATs) present in non-coding regions of certain mRNAs of pathogenic bacteria enable rapid upregulation of translation of virulence proteins when the temperature of the bacterium rises after entering a mammalian host. Rapid upregulation of translation of bacterial heat-shock proteins likewise is governed in part by RNATs. Turnover of mRNA may be regulated by temperature-sensitive RNA structures. Whereas the roles of temperature-sensitive RNA structures similar to RNATs in Eukarya and Archaea are largely unknown, there would appear to be a potential for all taxa to adaptively regulate their thermal physiology through exploitation of RNA-based thermosensory responses akin to those of bacteria. In animals, these responses might include regulation of translation of stress-induced proteins, alternative splicing of messenger RNA precursors, differential expression of allelic proteins, modulation of activities of small non-coding RNAs, regulation of mRNA turnover and control of RNA editing. New methods for predicting, detecting and experimentally modifying RNA secondary structure offer promising windows into these fascinating aspects of RNA biochemistry. Elucidating whether animals too have exploited the types of RNA thermosensing tools that are used so effectively by bacteria seems likely to provide exciting new insights into the mechanisms of evolutionary adaptation and acclimatization to temperature.

  View details for PubMedID 29472490

• Structural flexibility and protein adaptation to temperature: Molecular dynamics analysis of malate dehydrogenases of marine molluscs PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Dong, Y., Liao, M., Meng, X., Somero, G. N. 2018; 115 (6): 1274–79

  Abstract

  Orthologous proteins of species adapted to different temperatures exhibit differences in stability and function that are interpreted to reflect adaptive variation in structural "flexibility." However, quantifying flexibility and comparing flexibility across proteins has remained a challenge. To address this issue, we examined temperature effects on cytosolic malate dehydrogenase (cMDH) orthologs from differently thermally adapted congeners of five genera of marine molluscs whose field body temperatures span a range of ∼60 °C. We describe consistent patterns of convergent evolution in adaptation of function [temperature effects on KM of cofactor (NADH)] and structural stability (rate of heat denaturation of activity). To determine how these differences depend on flexibilities of overall structure and of regions known to be important in binding and catalysis, we performed molecular dynamics simulation (MDS) analyses. MDS analyses revealed a significant negative correlation between adaptation temperature and heat-induced increase of backbone atom movements [root mean square deviation (rmsd) of main-chain atoms]. Root mean square fluctuations (RMSFs) of movement by individual amino acid residues varied across the sequence in a qualitatively similar pattern among orthologs. Regions of sequence involved in ligand binding and catalysis-termed mobile regions 1 and 2 (MR1 and MR2), respectively-showed the largest values for RMSF. Heat-induced changes in RMSF values across the sequence and, importantly, in MR1 and MR2 were greatest in cold-adapted species. MDS methods are shown to provide powerful tools for examining adaptation of enzymes by providing a quantitative index of protein flexibility and identifying sequence regions where adaptive change in flexibility occurs.

  View details for PubMedID 29358381

• Thermal history and gape of individual Mytilus californianus correlate with oxidative damage and thermoprotective osmolytes JOURNAL OF EXPERIMENTAL BIOLOGY Gleason, L. U., Miller, L. P., Winnikoff, J. R., Somero, G. N., Yancey, P. H., Bratz, D., Dowd, W. 2017; 220 (22): 4292–4304

  Abstract

  The ability of animals to cope with environmental stress depends - in part - on past experience, yet knowledge of the factors influencing an individual's physiology in nature remains underdeveloped. We used an individual monitoring system to record body temperature and valve gaping behavior of rocky intertidal zone mussels (Mytilus californianus). Thirty individuals were selected from two mussel beds (wave-exposed and wave-protected) that differ in thermal regime. Instrumented mussels were deployed at two intertidal heights (near the lower and upper edges of the mussel zone) and in a continuously submerged tidepool. Following a 23-day monitoring period, measures of oxidative damage to DNA and lipids, antioxidant capacities (catalase activity and peroxyl radical scavenging) and tissue contents of organic osmolytes were obtained from gill tissue of each individual. Univariate and multivariate analyses indicated that inter-individual variation in cumulative thermal stress is a predominant driver of physiological variation. Thermal history over the outplant period was positively correlated with oxidative DNA damage. Thermal history was also positively correlated with tissue contents of taurine, a thermoprotectant osmolyte, and with activity of the antioxidant enzyme catalase. Origin site differences, possibly indicative of developmental plasticity, were only significant for catalase activity. Gaping behavior was positively correlated with tissue contents of two osmolytes. Overall, these results are some of the first to clearly demonstrate relationships between inter-individual variation in recent experience in the field and inter-individual physiological variation, in this case within mussel beds. Such micro-scale, environmentally mediated physiological differences should be considered in attempts to forecast biological responses to a changing environment.

  View details for PubMedID 29141883

• ): protein underpinnings of tolerance to body temperatures reaching 55°C. journal of experimental biology Liao, M., Zhang, S., Zhang, G., Chu, Y., Somero, G. N., Dong, Y. 2017; 220: 2066-2075

  Abstract

  Snails of the genus Echinolittorina are among the most heat-tolerant animals; they experience average body temperatures near 41-44°C in summer and withstand temperatures up to at least 55°C. Here, we demonstrate that heat stability of function (indexed by the Michaelis-Menten constant of the cofactor NADH, KM(NADH)) and structure (indexed by rate of denaturation) of cytosolic malate dehydrogenases (cMDHs) of two congeners (E. malaccana and E. radiata) exceeds values previously found for orthologs of this protein from less thermophilic species. The ortholog of E. malaccana is more heat stable than that of E. radiata, in keeping with the congeners' thermal environments. Only two inter-congener differences in amino acid sequence in these 332 residue proteins were identified. In both cases (positions 48 and 114), a glycine in the E. malaccana ortholog is replaced by a serine in the E. radiata protein. To explore the relationship between structure and function and to characterize how amino acid substitutions alter stability of different regions of the enzyme, we used molecular dynamics simulation methods. These computational methods allow determination of thermal effects on fine-scale movements of protein components, for example, by estimating the root mean square deviation in atom position over time and the root mean square fluctuation for individual residues. The minor changes in amino acid sequence favor temperature-adaptive change in flexibility of regions in and around the active sites. Interspecific differences in effects of temperature on fine-scale protein movements are consistent with the differences in thermal effects on binding and rates of heat denaturation.

  View details for DOI 10.1242/jeb.156935

  View details for PubMedID 28566358

• Untangling the roles of microclimate, behaviour and physiological polymorphism in governing vulnerability of intertidal snails to heat stress. Proceedings. Biological sciences Dong, Y., Li, X., Choi, F. M., Williams, G. A., Somero, G. N., Helmuth, B. 2017; 284 (1854)

  Abstract

  Biogeographic distributions are driven by cumulative effects of smaller scale processes. Thus, vulnerability of animals to thermal stress is the result of physiological sensitivities to body temperature (Tb), microclimatic conditions, and behavioural thermoregulation. To understand interactions among these variables, we analysed the thermal tolerances of three species of intertidal snails from different latitudes along the Chinese coast, and estimated potential Tb in different microhabitats at each site. We then empirically determined the temperatures at which heart rate decreased sharply with rising temperature (Arrhenius breakpoint temperature, ABT) and at which it fell to zero (flat line temperature, FLT) to calculate thermal safety margins (TSM). Regular exceedance of FLT in sun-exposed microhabitats, a lethal effect, was predicted for only one mid-latitude site. However, ABTs of some individuals were exceeded at sun-exposed microhabitats in most sites, suggesting physiological impairment for snails with poor behavioural thermoregulation and revealing inter-individual variations (physiological polymorphism) of thermal limits. An autocorrelation analysis of Tb showed that predictability of extreme temperatures was lowest at the hottest sites, indicating that the effectiveness of behavioural thermoregulation is potentially lowest at these sites. These results illustrate the critical roles of mechanistic studies at small spatial scales when predicting effects of climate change.

  View details for DOI 10.1098/rspb.2016.2367

  View details for PubMedID 28469014

• What Changes in the Carbonate System, Oxygen, and Temperature Portend for the Northeastern Pacific Ocean: A Physiological Perspective BIOSCIENCE Somero, G. N., Beers, J. M., Chan, F., Hill, T. M., Klinger, T., Litvin, S. Y. 2016; 66 (1): 14-26

  View details for DOI 10.1093/biosci/biv162

  View details for Web of Science ID 000368315900005

• Adaptations of protein structure and function to temperature: there is more than one way to 'skin a cat' JOURNAL OF EXPERIMENTAL BIOLOGY Fields, P. A., Dong, Y., Meng, X., Somero, G. N. 2015; 218 (12): 1801-1811

  Abstract

  Sensitivity to temperature helps determine the success of organisms in all habitats, and is caused by the susceptibility of biochemical processes, including enzyme function, to temperature change. A series of studies using two structurally and catalytically related enzymes, A4-lactate dehydrogenase (A4-LDH) and cytosolic malate dehydrogenase (cMDH) have been especially valuable in determining the functional attributes of enzymes most sensitive to temperature, and identifying amino acid substitutions that lead to changes in those attributes. The results of these efforts indicate that ligand binding affinity and catalytic rate are key targets during temperature adaptation: ligand affinity decreases during cold adaptation to allow more rapid catalysis. Structural changes causing these functional shifts often comprise only a single amino acid substitution in an enzyme subunit containing approximately 330 residues; they occur on the surface of the protein in or near regions of the enzyme that move during catalysis, but not in the active site; and they decrease stability in cold-adapted orthologs by altering intra-molecular hydrogen bonding patterns or interactions with the solvent. Despite these structure-function insights, we currently are unable to predict a priori how a particular substitution alters enzyme function in relation to temperature. A predictive ability of this nature might allow a proteome-wide survey of adaptation to temperature and reveal what fraction of the proteome may need to adapt to temperature changes of the order predicted by global warming models. Approaches employing algorithms that calculate changes in protein stability in response to a mutation have the potential to help predict temperature adaptation in enzymes; however, using examples of temperature-adaptive mutations in A4-LDH and cMDH, we find that the algorithms we tested currently lack the sensitivity to detect the small changes in flexibility that are central to enzyme adaptation to temperature.

  View details for DOI 10.1242/jeb.114298

  View details for Web of Science ID 000356497200003

• Adaptations of protein structure and function to temperature: there is more than one way to 'skin a cat'. journal of experimental biology Fields, P. A., Dong, Y., Meng, X., Somero, G. N. 2015; 218: 1801-1811

  Abstract

  Sensitivity to temperature helps determine the success of organisms in all habitats, and is caused by the susceptibility of biochemical processes, including enzyme function, to temperature change. A series of studies using two structurally and catalytically related enzymes, A4-lactate dehydrogenase (A4-LDH) and cytosolic malate dehydrogenase (cMDH) have been especially valuable in determining the functional attributes of enzymes most sensitive to temperature, and identifying amino acid substitutions that lead to changes in those attributes. The results of these efforts indicate that ligand binding affinity and catalytic rate are key targets during temperature adaptation: ligand affinity decreases during cold adaptation to allow more rapid catalysis. Structural changes causing these functional shifts often comprise only a single amino acid substitution in an enzyme subunit containing approximately 330 residues; they occur on the surface of the protein in or near regions of the enzyme that move during catalysis, but not in the active site; and they decrease stability in cold-adapted orthologs by altering intra-molecular hydrogen bonding patterns or interactions with the solvent. Despite these structure-function insights, we currently are unable to predict a priori how a particular substitution alters enzyme function in relation to temperature. A predictive ability of this nature might allow a proteome-wide survey of adaptation to temperature and reveal what fraction of the proteome may need to adapt to temperature changes of the order predicted by global warming models. Approaches employing algorithms that calculate changes in protein stability in response to a mutation have the potential to help predict temperature adaptation in enzymes; however, using examples of temperature-adaptive mutations in A4-LDH and cMDH, we find that the algorithms we tested currently lack the sensitivity to detect the small changes in flexibility that are central to enzyme adaptation to temperature.

  View details for DOI 10.1242/jeb.114298

  View details for PubMedID 26085658

• Proteomic analysis of cardiac response to thermal acclimation in the eurythermal goby fish Gillichthys mirabilis JOURNAL OF EXPERIMENTAL BIOLOGY Jayasundara, N., Tomanek, L., Dowd, W. W., Somero, G. N. 2015; 218 (9): 1359-1372

  Abstract

  Cardiac function is thought to play a central role in determining thermal optima and tolerance limits in teleost fishes. Investigating proteomic responses to temperature in cardiac tissues may provide insights into mechanisms supporting the thermal plasticity of cardiac function. Here, we utilized a global proteomic analysis to investigate changes in cardiac protein abundance in response to temperature acclimation (transfer from 13°C to 9, 19 and 26°C) in a eurythermal goby, Gillichthys mirabilis. Proteomic data revealed 122 differentially expressed proteins across acclimation groups, 37 of which were identified using tandem mass-spectrometry. These 37 proteins are involved in energy metabolism, mitochondrial regulation, iron homeostasis, cytoprotection against hypoxia, and cytoskeletal organization. Compared with the 9 and 26°C groups, proteins involved in energy metabolism increased in 19°C-acclimated fish, indicating an overall increase in the capacity for ATP production. Creatine kinase abundance increased in 9°C-acclimated fish, suggesting an important role for the phosphocreatine energy shuttle in cold-acclimated hearts. Both 9 and 26°C fish also increased abundance of hexosaminidase, a protein directly involved in post-hypoxia stress cytoprotection of cardiac tissues. Cytoskeletal restructuring appears to occur in all acclimation groups; however, the most prominent effect was detected in 26°C-acclimated fish, which exhibited significantly increased actin levels. Overall, proteomic analysis of cardiac tissue suggests that the capacity to adjust ATP-generating processes is crucial to the thermal plasticity of cardiac function. Furthermore, G. mirabilis may optimize cellular functions at temperatures near 19°C, which lies within the species' preferred temperature range.

  View details for DOI 10.1242/jeb.118760

  View details for Web of Science ID 000354115800017

  View details for PubMedID 25954043

• Temporal patterning of thermal acclimation: from behavior to membrane biophysics. journal of experimental biology Somero, G. 2015; 218: 167-169

  View details for DOI 10.1242/jeb.109843

  View details for PubMedID 25609779

• Master of all trades: thermal acclimation and adaptation of cardiac function in a broadly distributed marine invasive species, the European green crab, Carcinus maenas. journal of experimental biology Tepolt, C. K., Somero, G. N. 2014; 217: 1129-1138

  Abstract

  As global warming accelerates, there is increasing concern about how ecosystems may change as a result of species loss and replacement. Here, we examined the thermal physiology of the European green crab (Carcinus maenas Linnaeus 1758), a globally invasive species, along three parallel thermal gradients in its native and invasive ranges. At each site, we assessed cardiac physiology to determine heat and cold tolerance and acclimatory plasticity. We found that, overall, the species is highly tolerant of both heat and cold, and that it survives higher temperatures than co-occurring native marine crustaceans. Further, we found that both heat and cold tolerance are plastic in response to short-term acclimation (18-31 days at either 5 or 25°C). Comparing patterns within ranges, we found latitudinal gradients in thermal tolerance in the native European range and in the invasive range in eastern North America. This pattern is strongest in the native range, and likely evolved there. Because of a complicated invasion history, the latitudinal pattern in the eastern North American invasive range may be due either to rapid adaptation post-invasion or to adaptive differences between the ancestral populations that founded the invasion. Overall, the broad thermal tolerance ranges of green crabs, which may facilitate invasion of novel habitats, derive from high inherent eurythermality and acclimatory plasticity and potentially adaptive differentiation among populations. The highly flexible physiology that results from these capacities may represent the hallmark of a successful invasive species, and may provide a model for success in a changing world.

  View details for DOI 10.1242/jeb.093849

  View details for PubMedID 24671964

• The impact of ocean warming on marine organisms CHINESE SCIENCE BULLETIN Yao, C., Somero, G. N. 2014; 59 (5-6): 468-479

  View details for DOI 10.1007/s11434-014-0113-0

  View details for Web of Science ID 000331563100002

• Food availability, more than body temperature, drives correlated shifts in ATP-generating and antioxidant enzyme capacities in a population of intertidal mussels (Mytilus californianus) JOURNAL OF EXPERIMENTAL MARINE BIOLOGY AND ECOLOGY Dowd, W. W., Felton, C. A., Heymann, H. M., Kost, L. E., Somero, G. N. 2013; 449: 171-185

  View details for DOI 10.1016/j.jembe.2013.09.020

  View details for Web of Science ID 000334647500024

• Effects of temperature acclimation on cardiorespiratory performance of the Antarctic notothenioid Trematomus bernacchii POLAR BIOLOGY Jayasundara, N., Healy, T. M., Somero, G. N. 2013; 36 (7): 1047-1057

  View details for DOI 10.1007/s00300-013-1327-3

  View details for Web of Science ID 000321974900011

• Physiological plasticity of cardiorespiratory function in a eurythermal marine teleost, the longjaw mudsucker, Gillichthys mirabilis. journal of experimental biology Jayasundara, N., Somero, G. N. 2013; 216: 2111-2121

  Abstract

  An insufficient supply of oxygen under thermal stress is thought to define thermal optima and tolerance limits in teleost fish. When under thermal stress, cardiac function plays a crucial role in sustaining adequate oxygen supply for respiring tissues. Thus, adaptive phenotypic plasticity of cardiac performance may be critical for modifying thermal limits during temperature acclimation. Here we investigated effects of temperature acclimation on oxygen consumption, cardiac function and blood oxygen carrying capacity of a eurythermal goby fish, Gillichthys mirabilis, acclimated to 9, 19 and 26°C for 4 weeks. Acclimation did not alter resting metabolic rates or heart rates; no compensation of rates was observed at acclimation temperatures. However, under an acute heat ramp, warm-acclimated fish exhibited greater heat tolerance (CTmax=33.3, 37.1 and 38.9°C for 9°C-, 19°C- and 26°C-acclimated fish, respectively) and higher cardiac arrhythmia temperatures compared with 9°C-acclimated fish. Heart rates measured under an acute heat stress every week during 28 days of acclimation suggested that both maximum heart rates and temperature at onset of maximum heart rates changed over time with acclimation. Hemoglobin levels increased with acclimation temperature, from 35 g l(-1) in 9°C-acclimated fish to 60-80 g l(-1) in 19°C- and 26°C-acclimated fish. Oxygen consumption rates during recovery from acute heat stress showed post-stress elevation in 26°C-acclimated fish. These data, coupled with elevated resting metabolic rates and heart rates at warm temperatures, suggest a high energetic cost associated with warm acclimation in G. mirabilis. Furthermore, acclimatory capacity appears to be optimized at 19°C, a temperature shown by behavioral studies to be close to the species' preferred temperature.

  View details for DOI 10.1242/jeb.083873

  View details for PubMedID 23678101

• New Frontiers for Organismal Biology BIOSCIENCE Kueltz, D., Clayton, D. F., Robinson, G. E., Albertson, C., Carey, H. V., Cummings, M. E., Dewar, K., Edwards, S. V., Hofmann, H. A., Gross, L. J., Kingsolver, J. G., Meaney, M. J., Schlinger, B. A., Shingleton, A. W., Sokolowski, M. B., Somero, G. N., Stanzione, D. C., Todgham, A. E. 2013; 63 (6): 464-471

  View details for DOI 10.1525/bio.2013.63.6.8

  View details for Web of Science ID 000320743000008

• Thermal stress and cellular signaling processes in hemocytes of native (Mytilus californianus) and invasive (M. galloprovincialis) mussels: Cell cycle regulation and DNA repair. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology Yao, C., Somero, G. N. 2013; 165 (2): 159-168

  Abstract

  In a previous study using hemocytes from native and invasive congeners of Mytilus (Mytilus californianus and Mytilus galloprovincialis, respectively) we showed that DNA damage and cell signaling transduction processes related to the cellular stress response and apoptosis were induced by acute temperature stress. The present study extends this work by examining effects of acute heat- and cold stress on total hemocyte counts (THCs) and expression of key regulatory molecules involved in responding to stress: tumor suppressor factor (p53), cell cycle arrest activator (p21), and a DNA base excision repair enzyme (apurinic/apyrimidinic endonuclease (APE)). Hyperthermia (28 °C, 32 °C) led to significant decreases of THCs in both species. The extent of decrease in THC was temperature-, time-, and species-dependent; lower THC values were found in M. californianus, the more cold-adapted species. Western blot analyses of hemocyte extracts with antibodies specific for p53 protein, several site-specific phosphorylation states of p53, p21 protein, and APE indicated that heat- and cold (2 °C) stress induced a time-dependent activation of stress-related proteins in response to DNA damage; these stress-induced changes could govern cell cycle arrest or DNA damage repair. Our results show that the downstream regulatory response to temperature-induced cell damage may play an important role in deciding cellular fate following heat- and cold stress. Compared to M. californianus, the more warm-adapted M. galloprovincialis appears to have a higher temperature tolerance due to a lesser reduction in THC, faster signaling activation and transduction, and stronger DNA repair ability following heat stress.

  View details for DOI 10.1016/j.cbpa.2013.02.024

  View details for PubMedID 23454628

• A 1950s CLASSIC OF THERMAL ADAPTATION TO COLD JOURNAL OF EXPERIMENTAL BIOLOGY Somero, G. N. 2013; 216 (10): 1759-1761

  View details for DOI 10.1242/jeb.076398

  View details for Web of Science ID 000318483600006

  View details for PubMedID 23785104

• Lessons from cold-adapted enzymes: Can protein adaptation to temperature be simple and quick? Somero, G. OXFORD UNIV PRESS INC. 2013: E204

  View details for Web of Science ID 000316991401350

• Behavior and survival of Mytilus congeners following episodes of elevated body temperature in air and seawater JOURNAL OF EXPERIMENTAL BIOLOGY Dowd, W. W., Somero, G. N. 2013; 216 (3): 502-514

  Abstract

  Coping with environmental stress may involve combinations of behavioral and physiological responses. We examined potential interactions between adult mussels' simple behavioral repertoire - opening/closing of the shell valves - and thermal stress physiology in common-gardened individuals of three Mytilus congeners found on the West Coast of North America: two native species (M. californianus and M. trossulus) and one invasive species from the Mediterranean (M. galloprovincialis). We first continuously monitored valve behavior over three consecutive days on which body temperatures were gradually increased, either in air or in seawater. A temperature threshold effect was evident between 25 and 33°C in several behavioral measures. Mussels tended to spend much less time with the valves in a sealed position following exposure to 33°C body temperature, especially when exposed in air. This behavior could not be explained by decreases in adductor muscle glycogen (stores of this metabolic fuel actually increased in some scenarios), impacts of forced valve sealing on long-term survival (none observed in a second experiment), or loss of contractile function in the adductor muscles (individuals exhibited as many or more valve adduction movements following elevated body temperature compared with controls). We hypothesize that this reduced propensity to seal the valves following thermal extremes represents avoidance of hypoxia-reoxygenation cycles and concomitant oxidative stress. We further conjecture that prolonged valve gaping following episodes of elevated body temperature may have important ecological consequences by affecting species interactions. We then examined survival over a 90 day period following exposure to elevated body temperature and/or emersion, observing ongoing mortality throughout this monitoring period. Survival varied significantly among species (M. trossulus had the lowest survival) and among experimental contexts (survival was lowest after experiencing elevated body temperature in seawater). Surprisingly, we observed no cumulative impact on survival of 3 days relative to 1 day of exposure to elevated body temperature. The delayed mortality and context-specific outcomes we observed have important implications for the design of future experiments and for interpretation of field distribution patterns of these species. Ultimately, variation in the catalog of physiological and behavioral capacities among closely related or sympatric species is likely to complicate prediction of the ecological consequences of global change and species invasions.

  View details for DOI 10.1242/jeb.076620

  View details for Web of Science ID 000313740600026

  View details for PubMedID 23038732

• The impact of acute temperature stress on hemocytes of invasive and native mussels (Mytilus galloprovincialis and Mytilus californianus): DNA damage, membrane integrity, apoptosis and signaling pathways JOURNAL OF EXPERIMENTAL BIOLOGY Yao, C., Somero, G. N. 2012; 215 (24): 4267-4277

  Abstract

  We investigated the effects of acute heat stress and cold stress on cell viability, lysosome membrane stability, double- and single-stranded DNA breakage, and signaling mechanisms involved in cellular homeostasis and apoptosis in hemocytes of native and invasive mussels, Mytilus californianus and Mytilus galloprovincialis, respectively. Both heat stress (28, 32°C) and cold stress (2, 6°C) led to significant double- and single-stranded breaks in DNA. The type and extent of DNA damage were temperature and time dependent, as was caspase-3 activation, an indicator of apoptosis, which may occur in response to DNA damage. Hemocyte viability and lysosomal membrane stability decreased significantly under heat stress. Western blot analyses of hemocyte extracts with antibodies for proteins associated with cell signaling and stress responses [including members of the phospho-specific mitogen-activated protein kinase (MAPK) family c-JUN NH(2)-terminal kinase (JNK) and p38-MAPK, and apoptosis executor caspase-3] revealed that heat and cold stress induced a time-dependent activation of JNK, p38-MAPK and caspase-3 and that these signaling and stress responses differed between species. The thermal limits for activation of cell signaling processes linked to the repair of stress-induced damage may help determine cellular thermal tolerance limits. Our results show similarities in responses to cold and heat stress and suggest causal linkages between levels of DNA damage at both extremes of temperature and downstream regulatory responses, including induction of apoptosis. Compared with M. californianus, M. galloprovincialis might have a wider temperature tolerance due to a lower amount of single- and double-stranded DNA damage, faster signaling activation and transduction, and stronger repair ability against temperature stress.

  View details for DOI 10.1242/jeb.073577

  View details for Web of Science ID 000311480100010

  View details for PubMedID 22972891

• Functional Determinants of Temperature Adaptation in Enzymes of Cold- versus Warm-Adapted Mussels (Genus Mytilus) MOLECULAR BIOLOGY AND EVOLUTION Lockwood, B. L., Somero, G. N. 2012; 29 (10): 3061-3070

  Abstract

  Temperature is a strong selective force on the evolution of proteins due to its effects on higher orders of protein structure and, thereby, on critical protein functions like ligand binding and catalysis. Comparisons among orthologous proteins from differently thermally adapted species show consistent patterns of adaptive variation in function, but few studies have examined functional adaptation among multiple structural families of proteins. Thus, with our present state of knowledge, it is difficult to predict what fraction of the proteome will exhibit adaptive variation in the face of temperature increases of a few to several degrees Celsius, that is, temperature increases of the magnitude predicted by models of global warming. Here, we compared orthologous enzymes of the warm-adapted Mediterranean mussel Mytilus galloprovincialis and the cold-adapted Mytilus trossulus, a native of the North Pacific Ocean, species whose physiologies exhibit significantly different responses to temperature. We measured the effects of temperature on the kinetics (Michaelis-Menten constant-K(m)) of five enzymes that are important for ATP generation and that represent distinct protein structural families. Among phosphoglucomutase (PGM), phosphoglucose isomerase (PGI), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (GTP) (PEPCK), and isocitrate dehydrogenase (NADP) (IDH), only IDH orthologs showed significantly different thermal responses of K(m) between the two species. The K(m) of isocitrate of M. galloprovincialis-IDH was intrinsically lower and more thermally stable than that of M. trossulus-IDH and thus had higher substrate affinity at high temperatures. Two amino acid substitutions account for the functional differences between IDH orthologs, one of which allows for more hydrogen bonds to form near the mobile region of the active site in M. galloprovincialis-IDH. Taken together, our findings cast light on the targets of adaptive evolution in the context of climate change; only a minority of proteins might adapt to small changes in temperature, and these adaptations may involve only small changes in sequence.

  View details for DOI 10.1093/molbev/mss111

  View details for Web of Science ID 000309927900018

  View details for PubMedID 22491035

• The Physiology of Global Change: Linking Patterns to Mechanisms ANNUAL REVIEW OF MARINE SCIENCE, VOL 4 Somero, G. N. 2012; 4: 39-61

  Abstract

  Global change includes alterations in ocean temperature, oxygen availability, salinity, and pH, abiotic variables with strong and interacting influences on the physiology of all taxa. Physiological stresses resulting from changes in these four variables may cause broad biogeographic shifts as well as localized changes in distribution in mosaic habitats. To elucidate these causal linkages, I address the following questions: What types of physiological limitations can alter species' distributions and, in cases of extreme stress, cause extinctions? Which species are most threatened by these physiological challenges--and why? How do contents of genomes establish capacities to respond to global change, notably in the case of species that have evolved in highly stable habitats? How fully can phenotypic acclimatization offset abiotic stress? Can physiological measurements, including new molecular ("-omic") approaches, provide indices of the degree of sublethal stress an organism experiences? And can physiological evolution keep pace with global change?

  View details for DOI 10.1146/annurev-marine-120710-100935

  View details for Web of Science ID 000300634900004

  View details for PubMedID 22457968

• Latitudinal differences in Mytilus californianus thermal physiology MARINE ECOLOGY PROGRESS SERIES Logan, C. A., Kost, L. E., Somero, G. N. 2012; 450: 93-105

  View details for DOI 10.3354/meps09491

  View details for Web of Science ID 000302066000007

• Bruce D. Sidell (20 March 1948-8 February 2011) Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY Driedzic, W. R., Shick, J., Somero, G. N. 2011; 160 (3): 440–42

  View details for DOI 10.1016/j.cbpa.2011.06.025

  View details for Web of Science ID 000295305600016

  View details for PubMedID 21980604

• Bruce D. Sidell (20 March 1948-8 February 2011) Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY Driedzic, W. R., Shick, J., Somero, G. N. 2011; 154 (4): 437–39

  View details for DOI 10.1016/j.cbpc.2011.06.015

  View details for Web of Science ID 000295441200021

  View details for PubMedID 22010291

• Bruce D. Sidell (20 March 1948-8 February 2011) Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY Driedzic, W. R., Shick, J., Somero, G. N. 2011; 160 (2-3): 119–21

  View details for DOI 10.1016/j.cbpb.2011.06.005

  View details for Web of Science ID 000295440900009

  View details for PubMedID 21984995

• Bruce D. Sidell (20 March 1948-8 February 2011) Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS Driedzic, W. R., Shick, J., Somero, G. N. 2011; 6 (3): 335–36

  View details for DOI 10.1016/j.cbd.2011.06.005

  View details for Web of Science ID 000294938200010

• Bruce D. Sidell 20 March 1948-8 February 2011 OBITUARY JOURNAL OF EXPERIMENTAL BIOLOGY Driedzic, W., Shick, J., Somero, G. N. 2011; 214 (15): 2453–54

  View details for DOI 10.1242/jeb.060970

  View details for Web of Science ID 000292694500009

  View details for PubMedID 21877336

• Comparative physiology: a "crystal ball" for predicting consequences of global change AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Somero, G. N. 2011; 301 (1): R1-R14

  Abstract

  Comparative physiology offers powerful approaches for developing causal, mechanistic explanations of shifts in biogeographic patterning occurring in concert with global change. These analyses can identify the cellular loci and intensities of stress-induced perturbation and generate predictions about ecosystem alterations in a changing world. Congeneric species adapted to different abiotic conditions offer excellent study systems for these purposes. Several findings have emerged from such comparative studies: 1) In aquatic and terrestrial habitats, the most heat-tolerant ectotherms may be most threatened by further increases in temperature, due to proximity of these species' thermal optima and tolerance limits to current maximal ambient temperatures and limited capacities for acclimatization to higher temperatures. 2) Cardiac function is a "weak link" in acute thermal tolerance. 3) Stress-induced changes in gene expression comprise a graded response involving genes linked to damage repair, lysis of irreversibly damaged molecules, and downregulation of cell proliferation. Transcriptomic and proteomic analyses provide "biomarkers" for diagnosing degrees of stress. 4) Different abiotic stresses may have synergistic or opposing effects on gene expression, a complexity needing consideration when developing integrated pictures of effects of global change. 5) Adaptation of proteins can result from one to a few amino acid substitutions, which can occur at many sites in a protein, a discovery with implications for rates of adaptive evolution. 6) Greater thermal tolerance of invasive species may favor their replacement of natives. 7) Losses of protein-coding genes and temperature-responsive gene regulatory abilities in stenothermal ectotherms of the Southern Ocean may lead to broad extinctions.

  View details for DOI 10.1152/ajpregu.00719.2010

  View details for Web of Science ID 000292319800001

  View details for PubMedID 21430078

• Effects of thermal acclimation on transcriptional responses to acute heat stress in the eurythermal fish Gillichthys mirabilis (Cooper) AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Logan, C. A., Somero, G. N. 2011; 300 (6): R1373-R1383

  Abstract

  The capacities of eurythermal ectotherms to withstand wide ranges of temperature are based, in part, on abilities to modulate gene expression as body temperature changes, notably genes encoding proteins of the cellular stress response. Here, using a complementary DNA microarray, we investigated the sequence in which cellular stress response-linked genes are expressed during acute heat stress, to elucidate how severity of stress affects the categories of genes changing expression. We also studied how prior acclimation history affected gene expression in response to acute heat stress. Eurythermal goby fish (Gillichthys mirabilis) were acclimated to 9 ± 0.5, 19 ± 0.5, and 28 ± 0.5°C for 1 mo. Then fish were given an acute heat ramp (4°C/h), and gill tissues were sampled every +4°C to monitor gene expression. The average onset temperature for a significant change in expression during acute stress increased by ∼2°C for each ∼10°C increase in acclimation temperature. For some genes, warm acclimation appeared to obviate the need for expression change until the most extreme temperatures were reached. Sequential expression of different categories of genes reflected severity of stress. Regardless of acclimation temperature, the gene encoding heat shock protein 70 (HSP70) was upregulated strongly during mild stress; the gene encoding the proteolytic protein ubiquitin (UBIQ) was upregulated at slightly higher temperatures; and a gene encoding a protein involved in cell cycle arrest and apoptosis, cyclin-dependent kinase inhibitor 1B (CDKN1B), was upregulated only under extreme stress. The tiered, stress level-related expression patterns and the effects of acclimation on induction temperature yield new insights into the fundamental mechanisms of eurythermy.

  View details for DOI 10.1152/ajpregu.00689.2010

  View details for Web of Science ID 000291532000014

  View details for PubMedID 21411771

• Invasive and native blue mussels (genus Mytilus) on the California coast: The role of physiology in a biological invasion JOURNAL OF EXPERIMENTAL MARINE BIOLOGY AND ECOLOGY Lockwood, B. L., Somero, G. N. 2011; 400 (1-2): 167-174

  View details for DOI 10.1016/j.jembe.2011.02.022

  View details for Web of Science ID 000291143900015

• Transcriptomic responses to salinity stress in invasive and native blue mussels (genus Mytilus) MOLECULAR ECOLOGY Lockwood, B. L., Somero, G. N. 2011; 20 (3): 517-529

  Abstract

  The invasive marine mussel Mytilus galloprovincialis has displaced the native congener Mytilus trossulus from central and southern California, but the native species remains dominant at more northerly sites that have high levels of freshwater input. To determine the extent to which interspecific differences in physiological tolerance to low salinity might explain limits to the invasive species' biogeography, we used an oligonucleotide microarray to compare the transcriptional responses of these two species to an acute decrease in salinity. Among 6777 genes on the microarray, 117 genes showed significant changes that were similar between species, and 12 genes showed significant species-specific responses to salinity stress. Osmoregulation and cell cycle control were important aspects of the shared transcriptomic response to salinity stress, whereas the genes with species-specific expression patterns were involved in mRNA splicing, polyamine synthesis, exocytosis, translation, cell adhesion, and cell signalling. Forty-five genes that changed expression significantly during salinity stress also changed expression during heat stress, but the direction of change in expression was typically opposite for the two forms of stress. These results (i) provide insights into the role of changes in gene expression in establishing physiological tolerance to acute decreases in salinity, and (ii) indicate that transcriptomic differences between M. galloprovincialis and M. trossulus in response to salinity stress are subtle and involve only a minor fraction of the overall suite of gene regulatory responses.

  View details for DOI 10.1111/j.1365-294X.2010.04973.x

  View details for Web of Science ID 000286254700007

  View details for PubMedID 21199031

• Phosphorylation Events Catalyzed by Major Cell Signaling Proteins Differ in Response to Thermal and Osmotic Stress among Native (Mytilus californianus and Mytilus trossulus) and Invasive (Mytilus galloprovincialis) Species of Mussels PHYSIOLOGICAL AND BIOCHEMICAL ZOOLOGY Evans, T. G., Somero, G. N. 2010; 83 (6): 984-996

  Abstract

  Sharp environmental gradients encountered within the intertidal zone have driven the evolution of physiological adaptations that allow its inhabitants to maintain cellular function in the presence of fluctuating abiotic factors. These adaptations are mediated by gene-regulatory networks that, despite their inherent complexity, must remain evolvable and capable of responding to different selection pressures associated with specific ecological niches. Phosphorylation events catalyzed by cell-signaling enzymes represent a parsimonious mechanism to integrate new functional or regulatory properties into these gene-regulatory networks. In this study, proteins phosphorylated on consensus sequences for protein kinases A, B, and C; cyclin-dependent kinases; and mitogen-activated protein kinases, as well as the abundance of phosphorylated stress-activated protein kinase (phospho-SAPK/JNK), were quantified in order to ascertain whether phosphorylation events are divergent among native (Mytilus californianus and Mytilus trossulus) and invasive (Mytilus galloprovincialis) species of mussels that differ in their tolerance toward environmental stress. Abundances of phosphorylated substrate proteins for each of the major signaling proteins that were investigated, as well as the abundance of phospho-SAPK/JNK, differed both within and between species during thermal and osmotic stress. These data suggest that modulating protein function via phosphorylation may be an important mechanism to integrate novel properties into stress-regulatory networks. In turn, differential phosphorylation during environmental stress may contribute to species-specific tolerances toward abiotic stress, interspecies dynamics, and biogeographic patterns in Mytilus congeners.

  View details for DOI 10.1086/656192

  View details for Web of Science ID 000283992100009

  View details for PubMedID 20946068

• Transcriptomic responses to heat stress in invasive and native blue mussels (genus Mytilus): molecular correlates of invasive success JOURNAL OF EXPERIMENTAL BIOLOGY Lockwood, B. L., Sanders, J. G., Somero, G. N. 2010; 213 (20): 3548-3558

  Abstract

  Invasive species are increasingly prevalent in marine ecosystems worldwide. Although many studies have examined the ecological effects of invasives, little is known about the physiological mechanisms that might contribute to invasive success. The mussel Mytilus galloprovincialis, a native of the Mediterranean Sea, is a successful invader on the central and southern coasts of California, where it has largely displaced the native congener, Mytilus trossulus. It has been previously shown that thermal responses of several physiological traits may underlie the capacity of M. galloprovincialis to out-compete M. trossulus in warm habitats. To elucidate possible differences in stress-induced gene expression between these congeners, we developed an oligonucleotide microarray with 8874 probes representing 4488 different genes that recognized mRNAs of both species. In acute heat-stress experiments, 1531 of these genes showed temperature-dependent changes in expression that were highly similar in the two congeners. By contrast, 96 genes showed species-specific responses to heat stress, functionally characterized by their involvement in oxidative stress, proteolysis, energy metabolism, ion transport, cell signaling and cytoskeletal reorganization. The gene that showed the biggest difference between the species was the gene for the molecular chaperone small heat shock protein 24, which was highly induced in M. galloprovincialis and showed only a small change in M. trossulus. These different responses to acute heat stress may help to explain--and predict--the invasive success of M. galloprovincialis in a warming world.

  View details for DOI 10.1242/jeb.046094

  View details for Web of Science ID 000282541800018

  View details for PubMedID 20889835

• Transcriptional responses to thermal acclimation in the eurythermal fish Gillichthys mirabilis (Cooper 1864) AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Logan, C. A., Somero, G. N. 2010; 299 (3): R843-R852

  Abstract

  Thermal acclimation (acclimatization) capacity may be critical for determining how successfully an ectotherm can respond to temperature change, and adaptive shifts in gene expression may be pivotal for mediating these acclimatory responses. Using a cDNA microarray, we examined transcriptional profiles in gill tissue of a highly eurythermal goby fish, Gillichthys mirabilis, following 4 wk of acclimation to 9 degrees C, 19 degrees C, or 28 degrees C. Overall, gill transcriptomes were not strikingly different among acclimation groups. Of the 1,607 unique annotated genes on the array, only 150 of these genes (9%) were significantly different in expression among the three acclimation groups (ANOVA, false discovery rate < 0.05). Principal component analysis revealed that 59% of the variation in expression among these genes was described by an expression profile that is upregulated with increasing acclimation temperature. Gene ontology analysis of these genes identified protein biosynthesis, transport, and several metabolic categories as processes showing the greatest change in expression. Our results suggest that energetic costs of macromolecular turnover and membrane-localized transport rise with acclimation temperature. The upregulation of several classes of stress-related proteins, e.g., heat shock proteins, seen in the species' response to acute thermal stress was not observed in the long-term 28 degrees C-acclimated fish. The transcriptional differences found among the acclimation groups thus may reflect an acclimation process that has largely remedied the effects of acute thermal stress and established a new steady-state condition involving changes in relative energy costs for different processes. This pattern of transcriptional alteration in steady-state acclimated fish may be a signature of eurythermy.

  View details for DOI 10.1152/ajpregu.00306.2010

  View details for Web of Science ID 000281537500014

  View details for PubMedID 20610827

• Transcriptomic responses to heat-stress reveal the molecular basis for the success of invasive mussels Annual Meeting of the Society-for-Integrative-and-Comparative-Biology Lockwood, B. L., Sanders, J. G., Somero, G. N. OXFORD UNIV PRESS INC. 2010: E103–E103

  View details for Web of Science ID 000280297000409

• The physiology of climate change: how potentials for acclimatization and genetic adaptation will determine 'winners' and 'losers' JOURNAL OF EXPERIMENTAL BIOLOGY Somero, G. N. 2010; 213 (6): 912-920

  Abstract

  Physiological studies can help predict effects of climate change through determining which species currently live closest to their upper thermal tolerance limits, which physiological systems set these limits, and how species differ in acclimatization capacities for modifying their thermal tolerances. Reductionist studies at the molecular level can contribute to this analysis by revealing how much change in sequence is needed to adapt proteins to warmer temperatures--thus providing insights into potential rates of adaptive evolution--and determining how the contents of genomes--protein-coding genes and gene regulatory mechanisms--influence capacities for adapting to acute and long-term increases in temperature. Studies of congeneric invertebrates from thermally stressful rocky intertidal habitats have shown that warm-adapted congeners are most susceptible to local extinctions because their acute upper thermal limits (LT(50) values) lie near current thermal maxima and their abilities to increase thermal tolerance through acclimation are limited. Collapse of cardiac function may underlie acute and longer-term thermal limits. Local extinctions from heat death may be offset by in-migration of genetically warm-adapted conspecifics from mid-latitude 'hot spots', where midday low tides in summer select for heat tolerance. A single amino acid replacement is sufficient to adapt a protein to a new thermal range. More challenging to adaptive evolution are lesions in genomes of stenotherms like Antarctic marine ectotherms, which have lost protein-coding genes and gene regulatory mechanisms needed for coping with rising temperature. These extreme stenotherms, along with warm-adapted eurytherms living near their thermal limits, may be the major 'losers' from climate change.

  View details for DOI 10.1242/jeb.037473

  View details for Web of Science ID 000275002600013

  View details for PubMedID 20190116

• Can the giant snake predict palaeoclimate? NATURE Denny, M. W., Lockwood, B. L., Somero, G. N. 2009; 460 (7255): E3–E4

  View details for DOI 10.1038/nature08224

  View details for Web of Science ID 000268454300059

• Heterologous hybridization to a complementary DNA microarray reveals the effect of thermal acclimation in the endothermic bluefin tuna (Thunnus orientalis) MOLECULAR ECOLOGY Castilho, P. C., Buckley, B. A., Somero, G., Block, B. A. 2009; 18 (10): 2092-2102

  Abstract

  The temperature stress that pelagic fishes experience can induce physiological and behavioural changes that leave a signature in gene expression profiles. We used a functional genomics approach to identify genes that were up- or down-regulated following thermal stress in the Pacific bluefin tuna. Following the acclimation period, 113, 81 and 196 genes were found to be differentially expressed between the control (20 degrees C) and cold (15 degrees) treatment groups, in ventricle, red muscle and white muscle, respectively. The genes whose expression levels were responsive to thermal acclimation varied according to muscle fibre type, perhaps reflecting the tissue-specific degrees of endothermy characteristic of this species.

  View details for DOI 10.1111/j.1365-294X.2009.04174.x

  View details for Web of Science ID 000265774300005

  View details for PubMedID 19389180

• cDNA microarray analysis reveals the capacity of the cold-adapted Antarctic fish Trematomus bernacchii to alter gene expression in response to heat stress POLAR BIOLOGY Buckley, B. A., Somero, G. N. 2009; 32 (3): 403-415

  View details for DOI 10.1007/s00300-008-0533-x

  View details for Web of Science ID 000263389000009

• Temperature adaptation of cytosolic malate dehydrogenases of limpets (genus Lottia): differences in stability and function due to minor changes in sequence correlate with biogeographic and vertical distributions JOURNAL OF EXPERIMENTAL BIOLOGY Dong, Y., Somero, G. N. 2009; 212 (2): 169-177

  Abstract

  We characterized functional and structural properties of cytoplasmic malate dehydrogenases (cMDHs) from six limpets of the genus Lottia that have different vertical and latitudinal distributions. Particular attention was given to the cryptic species pair Lottia digitalis (northern occurring) and L. austrodigitalis (southern occurring) because of recent contraction in the southern range of L. digitalis and a northward range extension of L. austrodigitalis. As an index of adaptation of function, we measured the effects of temperature on the apparent Michaelis-Menten constant (K(m)) of the cofactor NADH (K(m)(NADH)). K(m)(NADH) values of cMDHs from the mid- to high-intertidal, low-latitude species L. scabra and L. gigantea were less sensitive to high temperature than those of cMDHs from the low- and mid-intertidal, high-latitude species L. scutum and L. pelta. cMDH of L. digitalis was more sensitive to high temperatures than the cMDH ortholog of L. austrodigitalis. Thermal stability (rate of loss of activity at 42.5 degrees C) showed a similar pattern of interspecific variation. Comparison of the deduced amino acid sequences showed that interspecific differences ranged from one to as many as 17 residues. Differences in K(m)(NADH) and thermal stability between orthologs of L. digitalis and L. austrodigitalis result from a single amino acid substitution. At position 291, the glycine residue in cMDH of L. digitalis is replaced by a serine in cMDH of L. austrodigitalis, a change that favors additional hydrogen bonding and reduced conformational entropy. This difference between closely related congeners demonstrates the role of minor alterations in protein sequence in temperature adaptation and suggests that such variation is important in governing shifts in biogeographic range in response to climate change.

  View details for DOI 10.1242/jeb.024505

  View details for Web of Science ID 000262011600008

  View details for PubMedID 19112135

• Protein-protein interactions enable rapid adaptive response to osmotic stress in fish gills. Communicative & integrative biology Evans, T. G., Somero, G. N. 2009; 2 (2): 94-96

  Abstract

  Cells respond to changes in osmolality with compensatory adaptations that re-establish ion homeostasis and repair disturbed aspects of cell structure and function. These physiologically complex processes can be separated into two functionally distinct cellular phases. The first phase operates to temporarily minimize cellular damage and stabilize critical cell functions necessary for survival. This phase is contingent upon the ability to generate a rapid adaptive response. For this reason, it occurs largely in the absence of de novo protein synthesis and instead relies upon modifying the activity of existing cellular proteins through protein-protein interactions and post-translational modifications. The second phase of the osmotic stress response is centered upon adjusting the expression of specific effector proteins required to re-establish cellular homeostasis. This phase is dependent on the completion of signal transduction events; as well the transcription and translation of target genes, and is therefore characterized by a significant temporal delay and not detected until several hours post exposure. Osmotic effector proteins central to the second phase, such as ion transporting proteins and organic osmolyte generating enzymes, have been studied in considerable detail. However, knowledge surrounding the first phase of the osmotic stress response is limited. This article focuses on recent insights into the players and interactions governing the first phase of the osmotic stress response with specific emphasis on protein-protein interactions.

  View details for PubMedID 19704899

• A microarray-based transcriptomic time-course of hyper- and hypo-osmotic stress signaling events in the euryhaline fish Gillichthys mirabilis: osmosensors to effectors JOURNAL OF EXPERIMENTAL BIOLOGY Evans, T. G., Somero, G. N. 2008; 211 (22): 3636-3649

  Abstract

  Cells respond to changes in osmolality with compensatory adaptations that re-establish ion homeostasis and repair disturbed aspects of cell structure and function. These physiological processes are highly complex, and require the coordinated activities of osmosensing, signal transducing and effector molecules. Although the critical role of effector proteins such as Na+, K+-ATPases and Na+/K+/Cl(-) co-transporters during osmotic stress are well established, comparatively little information is available regarding the identity or expression of the osmosensing and signal transduction genes that may govern their activities. To better resolve this issue, a cDNA microarray consisting of 9207 cDNA clones was used to monitor gene expression changes in the gill of the euryhaline fish Gillichthys mirabilis exposed to hyper- and hypo-osmotic stress. We successfully annotated 168 transcripts differentially expressed during the first 12 h of osmotic stress exposure. Functional classifications of genes encoding these transcripts reveal that a variety of biological processes are affected. However, genes participating in cell signaling events were the dominant class of genes differentially expressed during both hyper- and hypo-osmotic stress. Many of these genes have had no previously reported role in osmotic stress adaptation. Subsequent analyses used the novel expression patterns generated in this study to place genes within the context of osmotic stress sensing, signaling and effector events. Our data indicate multiple major signaling pathways work in concert to modify diverse effectors, and that these molecules operate within a framework of regulatory proteins.

  View details for DOI 10.1242/jeb.022160

  View details for Web of Science ID 000260540700020

  View details for PubMedID 18978229

• Rhythms of Gene Expression in a Fluctuating Intertidal Environment CURRENT BIOLOGY Gracey, A. Y., Chaney, M. L., Boomhower, J. P., Tyburczy, W. R., Connor, K., Somero, G. N. 2008; 18 (19): 1501-1507

  Abstract

  The physiological strategies that enable organisms to thrive in habitats where environmental factors vary dramatically on a daily basis are poorly understood. One of the most variable and unpredictable habitats on earth is the marine rocky intertidal zone located at the boundary between the terrestrial and marine environments. Mussels dominate rocky intertidal habitats throughout the world and, being sessile, endure wide variations in temperature, salinity, oxygen, and food availability due to diurnal, tidal, and climatic cycles. Analysis of gene-expression changes in the California ribbed mussel (Mytilus californianus) at different phases in the tidal cycle reveals that intertidal mussels exist in at least four distinct physiological states, corresponding to a metabolism and respiration phase, a cell-division phase, and two stress-response signatures linked to moderate and severe heat-stress events. The metabolism and cell-division phases appear to be functionally linked and are anticorrelated in time. The magnitudes and timings of these states varied by vertical position on the shore and appear to be driven by microhabitat conditions. The results provide new insights into the strategies that allow life to flourish in fluctuating environments and demonstrate the importance of time course data collected from field animals in situ in understanding organism-environment interactions.

  View details for DOI 10.1016/j.cub.2008.08.049

  View details for Web of Science ID 000260137900027

  View details for PubMedID 18848447

• Heat-Shock Protein 70 (Hsp70) Expression in Four Limpets of the Genus Lottia: Interspecific Variation in Constitutive and Inducible Synthesis Correlates With in situ Exposure to Heat Stress BIOLOGICAL BULLETIN Dong, Y., Miller, L. P., Sanders, J. G., Somero, G. N. 2008; 215 (2): 173-181

  Abstract

  Limpets of the genus Lottia occupy a broad vertical distribution on wave-exposed rocky shores, a range that encompasses gradients in the frequency and severity of thermal and desiccation stress brought on by aerial emersion. Using western blot analysis of levels of heat-shock protein 70 (Hsp70), we examined the heat-shock responses of four Lottia congeners: Lottia scabra and L. austrodigitalis, which occur in the high-intertidal zone, and L. pelta and L. scutum, which are restricted to the low- and mid-intertidal zones. Our results suggest distinct strategies of Hsp70 expression in limpets occupying different heights and orientations in the rocky intertidal zone. In freshly field-collected animals and in specimens acclimated at ambient temperature ( approximately 14 degrees C) for 14 days, the two high-intertidal species had higher constitutive levels of Hsp70 than the low- and mid-intertidal species. During aerial exposure to high temperatures, the two low-shore species and L. austrodigitalis exhibited an onset of Hsp70 expression at 28 degrees C; no induction of Hsp70 occurred in L. scabra. Our findings suggest that high-intertidal congeners of Lottia employ a "preparative defense" strategy involving maintenance of high constitutive levels of Hsp70 in their cells as a mechanism for protection against periods of extreme and unpredictable heat stress.

  View details for Web of Science ID 000260049800007

  View details for PubMedID 18840778

• Thermal limits and adaptation in marine Antarctic ectotherms: an integrative view PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES Poertner, H. O., Peck, L., Somero, G. 2007; 362 (1488): 2233-2258

  Abstract

  A cause and effect understanding of thermal limitation and adaptation at various levels of biological organization is crucial in the elaboration of how the Antarctic climate has shaped the functional properties of extant Antarctic fauna. At the same time, this understanding requires an integrative view of how the various levels of biological organization may be intertwined. At all levels analysed, the functional specialization to permanently low temperatures implies reduced tolerance of high temperatures, as a trade-off. Maintenance of membrane fluidity, enzyme kinetic properties (Km and k(cat)) and protein structural flexibility in the cold supports metabolic flux and regulation as well as cellular functioning overall. Gene expression patterns and, even more so, loss of genetic information, especially for myoglobin (Mb) and haemoglobin (Hb) in notothenioid fishes, reflect the specialization of Antarctic organisms to a narrow range of low temperatures. The loss of Mb and Hb in icefish, together with enhanced lipid membrane densities (e.g. higher concentrations of mitochondria), becomes explicable by the exploitation of high oxygen solubility at low metabolic rates in the cold, where an enhanced fraction of oxygen supply occurs through diffusive oxygen flux. Conversely, limited oxygen supply to tissues upon warming is an early cause of functional limitation. Low standard metabolic rates may be linked to extreme stenothermy. The evolutionary forces causing low metabolic rates as a uniform character of life in Antarctic ectothermal animals may be linked to the requirement for high energetic efficiency as required to support higher organismic functioning in the cold. This requirement may result from partial compensation for the thermal limitation of growth, while other functions like hatching, development, reproduction and ageing are largely delayed. As a perspective, the integrative approach suggests that the patterns of oxygen- and capacity-limited thermal tolerance are linked, on one hand, with the capacity and design of molecules and membranes, and, on the other hand, with life-history consequences and lifestyles typically seen in the permanent cold. Future research needs to address the detailed aspects of these interrelationships.

  View details for DOI 10.1098/rstb.2006.1947

  View details for Web of Science ID 000250644100005

  View details for PubMedID 17553776

  View details for PubMedCentralID PMC2443174

• An inducible 70 kDa-class heat shock protein is constitutively expressed during early development and diapause in the annual killifish Austrofundulus limnaeus CELL STRESS & CHAPERONES Podrabsky, J. E., Somero, G. N. 2007; 12 (3): 199-204

  Abstract

  The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds in regions of northern South America, where they survive the periodic drying of their habitat as diapausing embryos. These diapausing embryos are highly resistant to a number of environmental insults such as high temperature, dehydration, anoxia, and increased salinity. Molecular chaperones are known to play a role in stabilizing protein structure and function during events of cellular stress. Relative levels of heat shock protein (Hsp)70 were measured in developing and diapausing embryos of A. limnaeus using quantitative Western blots. An inducible or embryo-specific form of Hsp70 is expressed during embryonic development in A. limnaeus and is elevated during diapause II in this species. Constitutive expression of Hsp70 during development may afford these embryos protection from environmental stresses during development more quickly than relying on the induction of a classic heat shock response.

  View details for Web of Science ID 000249490200001

  View details for PubMedID 17915551

  View details for PubMedCentralID PMC1971235

• Extreme anoxia tolerance in embryos of the annual killifish Austrofundulus limnaeus: insights from a metabolomics analysis JOURNAL OF EXPERIMENTAL BIOLOGY Podrabsky, J. E., Lopez, J. P., Fan, T. W., Higashi, R., Somero, G. N. 2007; 210 (13): 2253-2266

  Abstract

  The annual killifish Austrofundulus limnaeus survives in ephemeral pond habitats by producing drought-tolerant diapausing embryos. These embryos probably experience oxygen deprivation as part of their normal developmental environment. We assessed the anoxia tolerance of A. limnaeus embryos across the duration of embryonic development. Embryos develop a substantial tolerance to anoxia during early development, which peaks during diapause II. This extreme tolerance of anoxia is retained during the first 4 days of post-diapause II development and is then lost. Metabolism during anoxia appears to be supported mainly by production of lactate, with alanine and succinate production contributing to a lesser degree. Anoxic embryos also accumulate large quantities of gamma-aminobutyrate (GABA), a potential protector of neural function. It appears that the suite of characters associated with normal development and entry into diapause II in this species prepares the embryos for long-term survival in anoxia even while the embryos are exposed to aerobic conditions. This is the first report of such extreme anoxia tolerance in a vertebrate embryo, and introduces a new model for the study of anoxia tolerance in vertebrates.

  View details for DOI 10.1242/jeb.005116

  View details for Web of Science ID 000248304900012

  View details for PubMedID 17575031

• Biochemical adaptations of notothenioid fishes: Comparisons between cold temperate South American and New Zealand species and Antarctic species COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY Petricorena, Z. L., Somero, G. N. 2007; 147 (3): 799-807

  Abstract

  Fishes of the perciform suborder Notothenioidei afford an excellent opportunity for studying the evolution and functional importance of diverse types of biochemical adaptation to temperature. Antarctic notothenioids have evolved numerous biochemical adaptations to stably cold waters, including antifreeze glycoproteins, which inhibit growth of ice crystals, and enzymatic proteins with cold-adapted specific activities (k(cat) values) and substrate binding abilities (K(m) values), which support metabolism at low temperatures. Antarctic notothenioids also exhibit the loss of certain biochemical traits that are ubiquitous in other fishes, including the heat-shock response (HSR) and, in members of the family Channichthyidae, hemoglobins and myoglobins. Tolerance of warm temperatures is also truncated in stenothermal Antarctic notothenioids. In contrast to Antarctic notothenioids, notothenioid species found in South American and New Zealand waters have biochemistries more reflective of cold-temperate environments. Some of the contemporary non-Antarctic notothenioids likely derive from ancestral species that evolved in the Antarctic and later "escaped" to lower latitude waters when the Antarctic Polar Front temporarily shifted northward during the late Miocene. Studies of cold-temperate notothenioids may enable the timing of critical events in the evolution of Antarctic notothenioids to be determined, notably the chronology of acquisition and amplification of antifreeze glycoprotein genes and the loss of the HSR. Genomic studies may reveal how the gene regulatory networks involved in acclimation to temperature differ between stenotherms like the Antarctic notothenioids and more eurythermal species like cold-temperate notothenioids. Comparative studies of Antarctic and cold-temperate notothenioids thus have high promise for revealing the mechanisms by which temperature-adaptive biochemical traits are acquired - or through which traits that cease to be of advantage under conditions of stable, near-freezing temperatures are lost - during evolution.

  View details for DOI 10.1016/j.cbpa.2006.09.028

  View details for Web of Science ID 000247360500024

  View details for PubMedID 17293146

• Inducible heat tolerance in Antarctic notothenioid fishes POLAR BIOLOGY Podrabsky, J. E., Somero, G. N. 2006; 30 (1): 39-43

  View details for DOI 10.1007/s00300-006-0157-y

  View details for Web of Science ID 000242439000005

• The cellular response to heat stress in the goby Gillichthys mirabilis: a cDNA microarray and protein-level analysis JOURNAL OF EXPERIMENTAL BIOLOGY Buckley, B. A., Gracey, A. Y., Somero, G. N. 2006; 209 (14): 2660-2677

  Abstract

  The cellular response to stress relies on the rapid induction of genes encoding proteins involved in preventing and repairing macromolecular damage incurred as a consequence of environmental insult. To increase our understanding of the scope of this response, a cDNA microarray, consisting of 9207 cDNA clones, was used to monitor gene expression changes in the gill and white muscle tissues of a eurythermic fish, Gillichthys mirabilis (Gobiidae) exposed to ecologically relevant heat stress. In each tissue, the induction or repression of over 200 genes was observed. These genes are associated with numerous biological processes, including the maintenance of protein homeostasis, cell cycle control, cytoskeletal reorganization, metabolic regulation and signal transduction, among many others. In both tissues, the molecular chaperones, certain transcription factors and a set of additional genes with various functions were induced in a similar manner; however, the majority of genes displayed tissue-specific responses. In gill, thermal stress induced the expression of the major structural components of the cytoskeleton, whereas these same genes did not respond to heat in muscle. In muscle, many genes involved in promoting cell growth and proliferation were repressed, perhaps to conserve energy for repair and replacement of damaged macromolecules, but a similar repression was not observed in the gill. Many of the observed changes in gene expression were similar to those described in model species whereas many others were unexpected. Measurements of the concentrations of the protein products of selected genes revealed that in each case an induction in mRNA synthesis correlated with an increase in protein production, though the timing and magnitude of the increase in protein was not consistently predicted by mRNA concentration, an important consideration in assessing the condition of the stressed cell using transcriptomic analysis.

  View details for DOI 10.1242/jeb.02292

  View details for Web of Science ID 000239640800011

  View details for PubMedID 16809457

• Following the heart: temperature and salinity effects on heart rate in native and invasive species of blue mussels (genus Mytilus) JOURNAL OF EXPERIMENTAL BIOLOGY Braby, C. E., Somero, G. N. 2006; 209 (13): 2554-2566

  Abstract

  The three species of blue mussels, Mytilus trossulus Gould 1850, M. edulis Linnaeus 1758 and M. galloprovincialis Lamarck 1819, have distinct global distribution patterns that are hypothesized to reflect differences in their tolerances of temperature and salinity. We examined effects on heart rate (beats min(-1)) of acute exposure and acclimation to different combinations of temperature and salinity to test this hypothesis and, in the context of the invasive success of M. galloprovincialis, to gain insights into the factors that may explain the replacement of the temperate Pacific native, M. trossulus, by this Mediterranean Sea invader along much of the California coast. Heart rate of M. trossulus was significantly higher than that of M. galloprovincialis, consistent with evolutionary adaptation to a lower habitat temperature (temperature compensation) in the former species. Heart rates of M. trossulus/M. galloprovincialis hybrids were intermediate between those of the parental species. Following acclimation to 14 degrees C and 21 degrees C, heart rates of all species exhibited partial compensation to temperature. Heart rate increased with rising temperature until a high temperature was reached at which point activity fell sharply, the high critical temperature (H(crit)). H(crit) increased with increasing acclimation temperature and differed among species in a pattern that reflected their probable evolutionary adaptation temperatures: M. galloprovincialis is more heat tolerant than the other two congeners. Ability to sustain heart function in the cold also reflected evolutionary history: M. trossulus is more cold tolerant than M. galloprovincialis. Heart rates for all three congeners decreased gradually in response to acute reductions in salinity until a low salinity (S(crit)) was reached at which heart rate dropped precipitously. S(crit) decreased with decreasing salinity of acclimation and was generally lowest for M. galloprovincialis. Mortality during acclimation under common garden conditions was greatest in M. trossulus and was highest at high acclimation temperatures and salinities. These intrinsic differences in basal heart rate, thermal and salinity responses, acclimatory capacity, and survivorship are discussed in the contexts of the species' biogeographic patterning and, for the invasive species M. galloprovincialis, the potential for further range expansion along the Pacific coast of North America.

  View details for DOI 10.1242/jeb.02259

  View details for Web of Science ID 000238421800025

  View details for PubMedID 16788038

• Have your say: welcome to the JEB Forum JOURNAL OF EXPERIMENTAL BIOLOGY Phillips, K., Hoppeler, H., Somero, G. 2006; 209 (10): 1785-1785

  View details for DOI 10.1242/jeb.02231

  View details for Web of Science ID 000237236500005

• Complex patterns of expression of heat-shock protein 70 across the southern biogeographical ranges of the intertidal mussel Mytilus californianus and snail Nucella ostrina JOURNAL OF BIOGEOGRAPHY Sagarin, R. D., Somero, G. N. 2006; 33 (4): 622-630

  View details for DOI 10.1111/j.1365-2699.2005.01403.x

  View details for Web of Science ID 000236247200006

• Ecological gradients and relative abundance of native (Mytilus trossulus) and invasive (Mytilus galloprovincialis) blue mussels in the California hybrid zone MARINE BIOLOGY Braby, C. E., Somero, G. N. 2006; 148 (6): 1249-1262

  View details for DOI 10.1007/s00227-005-0177-0

  View details for Web of Science ID 000236382800007

• Extreme anoxia tolerance in a vertebrate embryo Experimental Biology 2006 Annual Meeting Podrabsky, J. E., Lopez, J., Higashi, R., Fan, T., Somero, G. N. FEDERATION AMER SOC EXP BIOL. 2006: A827–A827

  View details for Web of Science ID 000236326200046

• Temperature sensitivities of cytosolic malate dehydrogenases from native and invasive species of marine mussels (genus Mytilus): sequence-function linkages and correlations with biogeographic distribution JOURNAL OF EXPERIMENTAL BIOLOGY Fields, P. A., Rudomin, E. L., Somero, G. N. 2006; 209 (4): 656-667

  Abstract

  The blue mussel Mytilus galloprovincialis, a native of the Mediterranean Sea, has invaded the west coast of North America in the past century, displacing the native blue mussel, Mytilus trossulus, from most of its former habitats in central and southern California. The invasive success of M. galloprovincialis is conjectured to be due, in part, to physiological adaptations that enable it to outperform M. trossulus at high temperatures. We have examined the structure and function of the enzyme cytosolic malate dehydrogenase (cMDH) from these species, as well as from the more distantly related ribbed mussel, Mytilus californianus, to characterize the effects of temperature on kinetic properties thought to exhibit thermal adaptation. The M. trossulus cMDH ortholog differs from the other cMDHs in a direction consistent with cold adaptation, as evidenced by a higher and more temperature-sensitive Michaelis-Menten constant for the cofactor NADH (Km(NADH)). This difference results from minor changes in sequence: the M. trossulus ortholog differs from the M. galloprovincialis ortholog by only two substitutions in the 334 amino acid monomer, and the M. californianus and M. trossulus orthologs differ by five substitutions. In each case, only one of these substitutions is non-conservative. To test the effects of individual substitutions on kinetic properties, we used site-directed mutagenesis to create recombinant cMDHs. Recombinant wild-type M. trossulus cMDH (rWT) has high Km(NADH) compared with mutants incorporating the non-conservative substitutions found in M. californianus and M. galloprovincialis - V114H and V114N, respectively - demonstrating that these mutations are responsible for the differences found in substrate affinity. Turnover number (kcat) is also higher in rWT compared with the two mutants, consistent with cold adaptation in the M. trossulus ortholog. Conversely, rWT and V114H appear more thermostable than V114N. Based on a comparison of Km(NADH) and kcat values among the orthologs, we propose that immersion temperatures are of greater selective importance in adapting kinetic properties than the more extreme temperatures that occur during emersion. The relative warm adaptation of M. galloprovincialis cMDH may be one of a suite of physiological characters that enhance the competitive ability of this invasive species in warm habitats.

  View details for DOI 10.1242/jeb.02036

  View details for Web of Science ID 000236042200012

  View details for PubMedID 16449560

• Evolutionary and acclimation-induced variation in the thermal limits of heart function in congeneric marine snails (Genus Tegula): Implications for vertical zonation BIOLOGICAL BULLETIN Stenseng, E., Braby, C. E., Somero, G. N. 2005; 208 (2): 138-144

  Abstract

  We analyzed the thermal limits of heart function for congeneric species of the marine snail Tegula that have different patterns of vertical zonation. T. funebralis is found in the low to mid-intertidal zone, and T. brunnea and T. montereyi live in the low-intertidal or subtidally. As indices of thermal limits of heart function, we used the temperature at which heart rate initially decreased rapidly during heating (the Arrhenius break temperature, or ABT) and the temperature at which heart ceased to beat with either heating or cooling (the flatline temperature, or FLT(hot) or FLT(cold), respectively). These three indices provide an estimate of the thermal range within which Tegula heart function is maintained. For field-acclimatized specimens, the thermal range of the high-intertidal T. funebralis was greater than those of its two lower-occurring congeners (higher ABT, higher FLT(hot), lower FLT(cold)). We also demonstrated the effects of constant thermal acclimation on the heart rate response to heat stress. Acclimation to 14 degrees C and 22 degrees C resulted in increases in ABT and FLT(hot), with the largest changes in T. brunnea and T. montereyi. Although T. funebralis is more heat tolerant and eurythermal than its two lower-occurring congeners, it can encounter field body temperatures that exceed ABT, indicating that T. funebralis faces a larger threat from heat stress, in situ. These findings are consistent with recent studies on other taxa of marine invertebrates that have shown, somewhat paradoxically, that warm-adapted, eurythermal intertidal species may be more impacted by global warming than congeneric subtidal species that are less heat tolerant.

  View details for Web of Science ID 000228618100008

  View details for PubMedID 15837963

• A cDNA microarray analysis of thermally responsive gene expression in a eurythermal goby, Gillichthys mirabilis Buckley, B. A., Gracey, A. Y., Somero, G. N. FEDERATION AMER SOC EXP BIOL. 2005: A1313

  View details for Web of Science ID 000227610902253

• Genomic responses to tides and temperature in Mytilis californianus Chancy, M. L., Boomhower, J., Gracey, A. Y., Somero, G. N. FEDERATION AMER SOC EXP BIOL. 2005: A1313

  View details for Web of Science ID 000227610902251

• Linking biogeography to physiology: Evolutionary and acclimatory adjustments of thermal limits. Frontiers in zoology Somero, G. N. 2005; 2 (1): 1-?

  Abstract

  Temperature-adaptive physiological variation plays important roles in latitudinal biogeographic patterning and in setting vertical distributions along subtidal-to-intertidal gradients in coastal marine ecosystems. Comparisons of congeneric marine invertebrates reveal that the most warm-adapted species may live closer to their thermal tolerance limits and have lower abilities to increase heat tolerance through acclimation than more cold-adapted species. In crabs and snails, heart function may be of critical importance in establishing thermal tolerance limits. Temperature-mediated shifts in gene expression may be critical in thermal acclimation. Transcriptional changes, monitored using cDNA microarrays, have been shown to differ between steady-state thermal acclimation and diurnal temperature cycling in a eurythermal teleost fish (Austrofundulus limnaeus). In stenothermal Antarctic notothenioid fish, losses in capacity for temperature-mediated gene expression, including the absence of a heat-shock response, may reduce the abilities of these species to acclimate to increased temperatures. Differences among species in thermal tolerance limits and in the capacities to adjust these limits may determine how organisms are affected by climate change.

  View details for PubMedID 15679952

• Peter Hochachka: Adventures in biochemical adaptation ANNUAL REVIEW OF PHYSIOLOGY Somero, G. N., Suarez, R. K. 2005; 67: 25-37

  Abstract

  Peter Hochachka was one of the most creative forces in the field of comparative physiology during the past half-century. His career was truly an exploratory adventure, in both intellectual and geographic senses. His broad comparative studies of metabolism in organisms as diverse as trout, tunas, oysters, squid, turtles, locusts, hummingbirds, seals, and humans revealed the adaptable features of enzymes and metabolic pathways that provide the biochemical bases for diverse lifestyles and environments. In its combined breadth and depth, no other corpus of work better illustrates the principle of "unity in diversity" that marks comparative physiology. Through his publications, his stimulating mentorship, his broad editorial services, and his continuous-and highly infectious-enthusiasm for his field, Peter Hochachka served as one of the most influential leaders in the transformation of comparative physiology.

  View details for Web of Science ID 000228406800003

  View details for PubMedID 15709951

• Adaptation of enzymes to temperature: searching for basic "strategies" COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY Somero, G. N. 2004; 139 (3): 321-333

  Abstract

  The pervasive influence of temperature on biological systems necessitates a suite of temperature--compensatory adaptations that span all levels of biological organization--from behavior to fine-scale molecular structure. Beginning about 50 years ago, physiological studies conducted with whole organisms or isolated tissues, by such pioneers of comparative thermal physiology as V.Ya. Alexandrov, T.H. Bullock, F.E.J. Fry, H. Precht, C.L. Prosser, and P.F. Scholander, began to document in detail the abilities of ectothermic animals to sustain relatively similar rates of metabolic activity at widely different temperatures of adaptation or acclimation. These studies naturally led to investigation of the roles played by enzymatic proteins in metabolic temperature compensation. Peter Hochachka's laboratory became an epicenter of this new focus in comparative physiology. The studies of the enzyme lactate dehydrogenase (LDH) that he initiated as a PhD student at Duke University in the mid-1960s and continued for several years at the University of British Columbia laid much of the foundation for subsequent studies of protein adaptation to temperature. Studies of orthologs of LDH have revealed the importance of conserving kinetic properties (catalytic rate constants (kcat) and Michaelis-Menten constants (Km) and structural stability during adaptation to temperature, and recently have identified the types of amino acid substitutions causing this adaptive variation. The roles of pH and low-molecular-mass organic solutes (osmolytes) in conserving the functional and structural properties of enzymes also have been elucidated using LDH. These studies, begun in Peter Hochachka's laboratory almost 40 years ago, have been instrumental in the development of a conceptual framework for the study of biochemical adaptation, a field whose origin can be traced largely to his creative influences. This framework emphasizes the complementary roles of three "strategies" of adaptation: (1) changes in amino acid sequence that cause adaptive variation in the kinetic properties and stabilities of proteins, (2) shifts in concentrations of proteins, which are mediated through changes in gene expression and protein turnover; and (3) changes in the milieu in which proteins function, which conserve the intrinsic properties of proteins established by their primary structure and modulate protein activity in response to physiological needs. This theoretical framework has helped guide research in adaptational biochemistry for many years and now stands poised to play a critical role in the post-genomic era, as physiologists grapple with the challenge of integrating the wealth of new data on gene sequences (genome), gene expression (transcriptome and proteome), and metabolic profiles (metabolome) into a realistic physiological context that takes into account the evolutionary histories and environmental relationships of species.

  View details for DOI 10.1016/j.cbpc.2004.05.003

  View details for Web of Science ID 000225554900005

  View details for PubMedID 15544958

• Preface to Peter Hochachka memorial volume COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY Somero, G. N. 2004; 139 (3): 311–12

  View details for DOI 10.1016/j.cbpc.2004.09.008

  View details for Web of Science ID 000225554900001

  View details for PubMedID 15544956

• Peter W. Hochachka 1937-2002 - Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY Somero, G. N. 2004; 139 (3): 313–14

  View details for Web of Science ID 000225554900002

• Changes in gene expression associated with acclimation to constant temperatures and fluctuating daily temperatures in an annual killifish Austrofundulus limnaeus JOURNAL OF EXPERIMENTAL BIOLOGY Podrabsky, J. E., Somero, G. N. 2004; 207 (13): 2237-2254

  Abstract

  Eurythermal ectotherms commonly thrive in environments that expose them to large variations in temperature on daily and seasonal bases. The roles played by alterations in gene expression in enabling eurytherms to adjust to these two temporally distinct patterns of thermal stress are poorly understood. We used cDNA microarray analysis to examine changes in gene expression in a eurythermal fish, Austrofundulus limnaeus, subjected to long-term acclimation to constant temperatures of 20, 26 and 37 degrees C and to environmentally realistic daily fluctuations in temperature between 20 degrees C and 37 degrees C. Our data reveal major differences between the transcriptional responses in the liver made during acclimation to constant temperatures and in response to daily temperature fluctuations. Control of cell growth and proliferation appears to be an important part of the response to change in temperature, based on large-scale changes in mRNA transcript levels for several key regulators of these pathways. However, cell growth and proliferation appear to be regulated by different genes in constant versus fluctuating temperature regimes. The gene expression response of molecular chaperones is also different between constant and fluctuating temperatures. Small heat shock proteins appear to play an important role in response to fluctuating temperatures whereas larger molecular mass chaperones such as Hsp70 and Hsp90 respond more strongly to chronic high temperatures. A number of transcripts that encode for enzymes involved in the biosynthesis of nitrogen-containing organic osmolytes have gene expression patterns that indicate a possible role for these 'chemical chaperones' during acclimation to chronic high temperatures and daily temperature cycling. Genes important for the maintenance of membrane integrity are highly responsive to temperature change. Changes in fatty acid saturation may be important in long-term acclimation and in response to fluctuating temperatures; however cholesterol metabolism may be most critical for short-term acclimation to fluctuating temperatures. The variable effect of temperature on the expression of genes with daily rhythms of expression indicates that there is a complex interaction between the temperature cycle and daily rhythmicity in gene expression. A number of new hypotheses concerning temperature acclimation in fish have been generated as a result of this study. The most notable of these hypotheses is the possibility that the high mobility group b1 (HMGB1) protein, which plays key roles in the assembly of transcription initiation and enhanceosome complexes, may act as a compensatory modulator of transcription in response to temperature, and thus as a global gene expression temperature sensor. This study illustrates the utility of cDNA microarray approaches in both hypothesis-driven and 'discovery-based' investigations of environmental effects on organisms.

  View details for DOI 10.1242/jeb.01016

  View details for Web of Science ID 000222727900016

  View details for PubMedID 15159429

• Evolutionary convergence in adaptation of proteins to temperature: A(4)-Lactate dehydrogenases of pacific damselfishes (Chromis spp.) MOLECULAR BIOLOGY AND EVOLUTION Johns, G. C., Somero, G. N. 2004; 21 (2): 314-320

  Abstract

  We have compared the kinetic properties (Michaelis-Menten constant [K(m)] and catalytic rate constant [k(cat)]) and amino acid sequences of orthologs of lactate dehydrogenase-A (A(4)-LDH) from congeners of Pacific damselfishes (genus Chromis) native to cold-temperate and tropical habitats to elucidate mechanisms of enzymatic adaptation to temperature. Specifically, we determined whether the sites of adaptive variation and the types of amino acids involved in substitutions at these sites were similar in the Chromis orthologs and other orthologs of warm-adapted and cold-adapted A(4)-LDH previously studied. We report striking evolutionary convergence in temperature adaptation of this protein and present further support for the hypothesis that enzyme adaptation to temperature involves subtle amino acid changes at a few sites that affect the mobility of the portions of the enzyme that are involved in rate-determining catalytic conformational changes. We tested the predicted effects of differences in sequence using site-directed mutagenesis. A single amino acid substitution in a key hinge region of the A(4)-LDH molecule is sufficient to change the kinetic characteristics of a temperate A(4)-LDH to that of a tropical ortholog. This substitution is at the same location that was identified in previous studies of adaptive variation in A(4)-LDH and was hypothesized to be important in adjusting K(m) and k(cat). Our results suggest that certain sites within an enzyme, notably those that establish the energy changes associated with rate-limiting movements of protein structure during catalysis, are "hot spots" of adaptation and that common types of amino acid substitutions occur at these sites to adapt structural "flexibility" and kinetic properties. Thus, despite the wide array of options that proteins have to adjust their structural stabilities in the face of thermal stress, the adaptive changes that couple "flexibility" to alterations of function may be limited in their diversity.

  View details for DOI 10.1093/molbev/msh021

  View details for Web of Science ID 000220083300014

  View details for PubMedID 14660697

• Influences of thermal acclimation and acute temperature change on the motility of epithelial wound-healing cells (keratocytes) of tropical, temperate and Antarctic fish JOURNAL OF EXPERIMENTAL BIOLOGY Ream, R. A., Theriot, J. A., Somero, G. N. 2003; 206 (24): 4539-4551

  Abstract

  The ability to heal superficial wounds is an important element in an organism's repertoire of adaptive responses to environmental stress. In fish, motile cells termed keratocytes are thought to play important roles in the wound-healing process. Keratocyte motility, like other physiological rate processes, is likely to be dependent on temperature and to show adaptive variation among differently thermally adapted species. We have quantified the effects of acute temperature change and thermal acclimation on actin-based keratocyte movement in primary cultures of keratocytes from four species of teleost fish adapted to widely different thermal conditions: two eurythermal species, the longjaw mudsucker Gillichthys mirabilis (environmental temperature range of approximately 10-37 degrees C) and a desert pupfish, Cyprinodon salinus (10-40 degrees C), and two species from stable thermal environments, an Antarctic notothenioid, Trematomus bernacchii (-1.86 degrees C), and a tropical clownfish, Amphiprion percula (26-30 degrees C). For all species, keratocyte speed increased with increasing temperature. G. mirabilis and C. salinus keratocytes reached maximal speeds at 25 degrees C and 35 degrees C, respectively, temperatures within the species' normal thermal ranges. Keratocytes of the stenothermal species continued to increase in speed as temperature increased above the species' normal temperature ranges. The thermal limits of keratocyte motility appear to exceed those of whole-organism thermal tolerance, notably in the case of T. bernacchii. Keratocytes of T. bernacchii survived supercooling to -6 degrees C and retained motility at temperatures as high as 20 degrees C. Mean keratocyte speed was conserved at physiological temperatures for the three temperate and tropical species, which suggests that a certain rate of motility is advantageous for wound healing. However, there was no temperature compensation in speed of movement for keratocytes of the Antarctic fish, which have extremely slow rates of movement at physiological temperatures. Keratocytes from all species moved in a persistent, unidirectional manner at low temperatures but at higher temperatures began to take more circular or less-persistent paths. Thermal acclimation affected the persistence and turning magnitude of keratocytes, with warmer acclimations generally yielding more persistent cells that followed straighter paths. However, acclimation did not alter the effect of experimental temperature on cellular speed. These findings suggest that more than one temperature-sensitive mechanism may govern cell motility: the rate-limiting process(es) responsible for speed is distinct from the mechanism(s) underlying directionality and persistence. Keratocytes represent a useful study system for evaluating the effects of temperature at the cellular level and for studying adaptive variation in actin-based cellular movement and capacity for wound healing.

  View details for Web of Science ID 000187394300018

  View details for PubMedID 14610038

• Protein adaptations to temperature and pressure: complementary roles of adaptive changes in amino acid sequence and internal milieu Symposium on Function of Marine Organisms: Mechanisms of Adaption to Diverse Environments Somero, G. N. ELSEVIER SCIENCE INC. 2003: 577–91

  Abstract

  Retention of required structural and functional properties of proteins in species adapted to different temperatures and pressures is achieved through variation in amino acid sequence and accumulation of small organic solutes that stabilize protein traits. Conservation of ligand binding and catalytic rate can be achieved by minor differences in sequence. For orthologs of lactate dehydrogenase-A (A(4)-LDH) temperature adaptation may involve only a single amino acid substitution. Adaptation involves changes in conformational mobility of regions of A(4)-LDH that undergo movement during ligand binding, movements that are rate-limiting to catalysis. A model that integrates adaptations in sequence and intracellular milieu is developed on the basis of conformational microstates. Although orthologs of different thermally adapted species vary in stability, at physiological temperatures it is hypothesized that a similar ensemble of conformational microstates exists for all orthologs. Organic solutes stabilize this ensemble of microstates. Differences among orthologs in responses to organic solutes at a common temperature lead to similar responses at normal body temperatures. Because protein stability increases at high protein concentrations, intrinsic stabilities of proteins may reflect the protein concentrations of the cellular compartments in which they occur. Protein-stabilizing solutes like trimethylamine-N-oxide (TMAO) conserve protein function and structure at elevated hydrostatic pressures.

  View details for DOI 10.1016/S1096-4959(03)00215-X

  View details for Web of Science ID 000187366400002

  View details for PubMedID 14662287

• Local selection and latitudinal variation in a marine predator-prey interaction SCIENCE Sanford, E., Roth, M. S., Johns, G. C., Wares, J. P., Somero, G. N. 2003; 300 (5622): 1135-1137

  Abstract

  Although pairs of species often interact over broad geographic ranges, few studies have explored how interactions vary across these large spatial scales. Surveys along 1500 kilometers of the Pacific coast of North America documented marked variation in the frequency of predation by the snail Nucella canaliculata on the intertidal mussel Mytilus californianus. Laboratory rearing experiments suggest that regional differences in drilling behavior have a genetic basis, and mitochondrial sequence variation confirms that gene flow is low among these snail populations. Marine communities separated by hundreds of kilometers may have intrinsically different dynamics, with interactions shaped by restricted gene flow and spatially varying selection.

  View details for Web of Science ID 000182886500042

  View details for PubMedID 12750518

• Base compositions of genes encoding alpha-actin and lactate dehydrogenase-A from differently adapted vertebrates show no temperature-adaptive variation in G+C content MOLECULAR BIOLOGY AND EVOLUTION Ream, R. A., Johns, G. C., Somero, G. N. 2003; 20 (1): 105-110

  Abstract

  There is a long-standing debate in molecular evolution concerning the putative importance of GC content in adapting the thermal stabilities of DNA and RNA. Most studies of this relationship have examined broad-scale compositional patterns, for example, total GC percentages in genomes and occurrence of GC-rich isochores. Few studies have systematically examined the GC contents of individual orthologous genes from differently thermally adapted species. When this has been done, the emphasis has been on comparing large numbers of genes in only a few species. We have approached the GC-adaptation temperature hypothesis in a different manner by examining patterns of base composition of genes encoding lactate dehydrogenase-A (ldh-a) and alpha-actin (alpha-actin) from 51 species of vertebrates whose adaptation temperatures ranged from -1.86 degrees C (Antarctic fishes) to approximately 45 degrees C (desert reptile). No significant positive correlation was found between any index of GC content (GC content of the entire sequence, GC content of the third codon position [GC(3)], and GC content at fourfold degenerate sites [GC(4)]) and any index of adaptation temperature (maximal, mean, or minimal body temperature). For alpha-actin, slopes of regression lines for all comparisons did not differ significantly from zero. For ldh-a, negative correlations between adaptation temperature and total GC content, GC(3), and GC(4) were observed but were shown to be due entirely to phylogenetic influences (as revealed by independent contrast analyses). This comparison of GC content across a wide range of ectothermic ("cold-blooded") and endothermic ("warm-blooded") vertebrates revealed that frogs of the genus Xenopus, which have commonly been used as a representative cold-blooded species, in fact are outliers among ectotherms for the alpha-actin analyses, raising concern about the appropriateness of choosing these amphibians as representative of ectothermic vertebrates in general. Our study indicates that, whereas GC contents of isochores may show variation among different classes of vertebrates, there is no consistent relationship between adaptation temperature and the percentage of thermal stability-enhancing G + C base pairs in protein-coding genes.

  View details for DOI 10.1093/molbev/msg008

  View details for Web of Science ID 000180243700014

  View details for PubMedID 12519912

• Obituary: Peter W. Hochachka (1937-2002). Comparative biochemistry and physiology. Toxicology & pharmacology : CBP Somero, G. N. 2002; 133 (4): 471-473

  View details for PubMedID 12841218

• Peter W. Hochachka - 1937-2002 - Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR AND INTEGRATIVE PHYSIOLOGY Somero, G. N. 2002; 133 (4): 901–3

  View details for DOI 10.1016/S1095-6433(02)00288-X

  View details for Web of Science ID 000179966900001

• Peter W. Hochachka 1937-2002 - Obituary COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY Somero, G. N. 2002; 133 (4): 457–59

  View details for DOI 10.1016/S1096-4959(02)00223-3

  View details for Web of Science ID 000180030500001

• Thermal physiology and vertical zonation of intertidal animals: Optima, limits, and costs of living Annual Meeting of the Society-for-Integrative-and-Comparative-Biology Somero, G. N. OXFORD UNIV PRESS INC. 2002: 780–89

  Abstract

  Temperature's pervasive effects on physiological systems are reflected in the suite of temperature-adaptive differences observed among species from different thermal niches, such as species with different vertical distributions (zonations) along the subtidal to intertidal gradient. Among the physiological traits that exhibit adaptive variation related to vertical zonation are whole organism thermal tolerance, heart function, mitochondrial respiration, membrane static order (fluidity), action potential generation, protein synthesis, heat-shock protein expression, and protein thermal stability. For some, but not all, of these thermally sensitive traits acclimatization leads to adaptive shifts in thermal optima and limits. The costs associated with repairing thermal damage and adapting systems through acclimatization may contribute importantly to energy budgets. These costs arise from such sources as: (i) activation and operation of the heat-shock response, (ii) replacement of denatured proteins that have been removed through proteolysis, (iii) restructuring of cellular membranes ("homeoviscous" adaptation), and (iv) pervasive shifts in gene expression (as gauged by using DNA microarray techniques). The vertical zonation observed in rocky intertidal habitats thus may reflect two distinct yet closely related aspects of thermal physiology: (i) intrinsic interspecific differences in temperature sensitivities of physiological systems, which establish thermal optima and tolerance limits for species; and (ii) 'cost of living' considerations arising from sub-lethal perturbation of these physiological systems, which may establish an energetics-based limitation to the maximal height at which a species can occur. Quantifying the energetic costs arising from heat stress represents an important challenge for future investigations.

  View details for Web of Science ID 000180793500010

  View details for PubMedID 21708776

• Temperature adaptation in Gillichthys (Teleost : Gobiidae) A(4)-lactate dehydrogenases: identical primary structures produce subtly different conformations JOURNAL OF EXPERIMENTAL BIOLOGY Fields, P. A., Kim, Y. S., Carpenter, J. F., Somero, G. N. 2002; 205 (9): 1293-1303

  Abstract

  Alternative conformations of proteins underlie a variety of biological phenomena, from prion proteins that cause spongiform encephalopathies to membrane channel proteins whose conformational changes admit or exclude specific ions. In this paper, we argue that conformational differences within globular 'housekeeping' enzymes may allow rapid adaptation to novel environments. Muscle-type lactate dehydrogenases (A(4)-LDHs) from the gobies Gillichthys seta and G. mirabilis have identical amino acid sequences but show potentially adaptive differences in substrate affinity (apparent Michaelis constants for pyruvate, K(m)(PYR)) as well as differences in thermal stability. We examined the A(4)-LDH of each species using fluorescence spectroscopy, near- and far-ultraviolet circular dichroism (CD) spectroscopy and hydrogen/deuterium exchange (H/D) Fourier-transform infrared spectroscopy to determine whether structural differences were apparent, the extent to which structural differences could be related to differences in conformational flexibility and whether specific changes in secondary or tertiary structure could be defined. The fluorescence spectra and far-ultraviolet CD spectra of the A(4)-LDH from the two species were indistinguishable, suggesting that the two conformations are very similar in secondary and tertiary structure. Apparent melting temperatures (T(m)) followed by fluorescence and CD spectroscopy confirmed that the G. mirabilis A(4)-LDH is more thermally stable than the G. seta form. H/D exchange kinetics of Gillichthys A(4)-LDH was described using double-exponential regression; at 20 degrees C, G. seta A(4)-LDH has a higher exchange constant, indicating a more flexible and open structure. At 40 degrees C, the difference in H/D exchange constants disappears. Second-derivative analysis of H/D exchange infrared spectra indicates that alpha-helical, but not beta-sheet structure, differs in conformational flexibility between the two forms. Second-derivative ultraviolet spectra indicate that at least one of the five tyrosyl residues in the Gillichthys LDH-A monomer is located in a more hydrophobic environment in the G. mirabilis form. Homology models of A(4)-LDH indicate that Tyr246 is the most likely candidate to experience a modified environment because it is involved in subunit contacts within the homotetramer and sits in a hinge between a static alpha-helix and one involved in catalytic conformational changes. Subtle differences in conformation around this residue probably play a role both in altered flexibility and in the potentially adaptive differences in kinetics between the two A(4)-LDH forms.

  View details for Web of Science ID 000175725600011

  View details for PubMedID 11948206

• Interspecific- and acclimation-induced variation in levels of heat-shock proteins 70 (hsp70) and 90 (hsp90) and heat-shock transcription factor-1 (HSF1) in congeneric marine snails (genus Tegula): implications for regulation of hsp gene expression JOURNAL OF EXPERIMENTAL BIOLOGY Tomanek, L., Somero, G. N. 2002; 205 (5): 677-685

  Abstract

  In our previous studies of heat-shock protein (hsp) expression in congeneric marine gastropods of the genus Tegula, we observed interspecific and acclimation-induced variation in the temperatures at which heat-shock gene expression is induced (T(on)). To investigate the factors responsible for these inter- and intraspecific differences in T(on), we tested the predictions of the 'cellular thermometer' model for the transcriptional regulation of hsp expression. According to this model, hsps not active in chaperoning unfolded proteins bind to a transcription factor, heat-shock factor-1 (HSF1), thereby reducing the levels of free HSF1 that are available to bind to the heat-shock element, a regulatory element upstream of hsp genes. Under stress, hsps bind to denatured proteins, releasing HSF1, which can now activate hsp gene transcription. Thus, elevated levels of heat-shock proteins of the 40, 70 and 90 kDa families (hsp 40, hsp70 and hsp90, respectively) would be predicted to elevate T(on). Conversely, elevated levels of HSF1 would be predicted to decrease T(on). Following laboratory acclimation to 13, 18 and 23 degrees C, we used solid-phase immunochemistry (western analysis) to quantify endogenous levels of two hsp70 isoforms (hsp74 and hsp72), hsp90 and HSF1 in the low- to mid-intertidal species Tegula funebralis and in two subtidal to low-intertidal congeners, T. brunnea and T. montereyi. We found higher endogenous levels of hsp72 (a strongly heat-induced isoform) at 13 and 18 degrees C in T. funebralis in comparison with T. brunnea and T. montereyi. However, T. funebralis also had higher levels of HSF1 than its congeners. The higher levels of HSF1 in T. funebralis cannot, within the framework of the cellular thermometer model, account for the higher T(on) observed for this species, although they may explain why T. funebralis is able to induce the heat-shock response more rapidly than T. brunnea. However, the cellular thermometer model does appear to explain the cause of the increases in T(on) that occurred during warm acclimation of the two subtidal species, in which warm acclimation was accompanied by increased levels of hsp72, hsp74 and hsp90, whereas levels of HSF1 remained stable. T. funebralis, which experiences greater heat stress than its subtidal congeners, consistently had higher ratios of hsp72 to hsp74 than its congeners, although the sum of levels of the two isoforms was similar for all three species except at the highest acclimation temperature (23 degrees C). The ratio of hsp72 to hsp74 may provide a more accurate estimate of environmental heat stress than the total concentrations of both hsp70 isoforms.

  View details for Web of Science ID 000174507900011

  View details for PubMedID 11907057

• Metabolic cold adaptation in Antarctic fishes: evidence from enzymatic activities of brain MARINE BIOLOGY Kawall, H. G., Torres, J. J., Sidell, B. D., Somero, G. N. 2002; 140 (2): 279-286

  View details for DOI 10.1007/s002270100695

  View details for Web of Science ID 000174672600007

• Phylogenetic relationships and biochemical properties of the duplicated cytosolic and mitochondrial isoforms of malate dehydrogenase from a teleost fish, Sphyraena idiastes JOURNAL OF MOLECULAR EVOLUTION Lin, J. J., Yang, T. H., Wahlstrand, B. D., Fields, P. A., Somero, G. N. 2002; 54 (1): 107-117

  Abstract

  Unlike birds and mammals, teleost fish express two paralogous isoforms (paralogues) of cytosolic malate dehydrogenase (cMDH; EC 1.1.1.37; NAD+: malate oxidoreductase) whose evolutionary relationships to the single cMDH of tetrapods are unknown. We sequenced complementary DNAs for both cMDHs and the mitochondrial isoform (mMDH) of the fish Sphyraena idiastes (south temperate barracuda) and compared the sequences, kinetic properties, and thermal stabilities of the three isoforms with those of mammalian orthologues. Both fish cMDHs comprise 333 residues and have subunit masses of approximately 36 kDa. One cytosolic isoform, cMDH-S, was significantly more heat-stable than either the other cMDH (cMDH-L) or mMDH. In contradiction to the generally accepted model of vertebrate cMDH evolution, our phylogenetic analysis indicates that the duplication of the fish cytosolic paralogues occurred after the divergence of the lineages leading to teleosts and tetrapods. cMDH-L and cMDH-S differed in optimal concentrations of substrates and cofactors and apparent Michaelis-Menten constants, suggesting that the two paralogues may play distinct physiological roles. Differences in intrinsic thermal stability among MDH paralogues may reflect different degrees of stabilization in vivo by extrinsic stabilizers, notably protein concentration in the case of mMDH. Thermal stabilities of porcine mMDH and cMDH-L, but not cMDH-S, were significantly increased when denaturation was measured at a high protein (bovine serum albumin; BSA) concentration, but the BSA-induced stabilization reduced the catalytic activity.

  View details for Web of Science ID 000172518200013

  View details for PubMedID 11734904

• Intrinsic versus extrinsic stabilization of enzymes - The interaction of solutes and temperature on A(4)-lactate dehydrogenase orthologs from warm-adapted and cold-adapted marine fishes EUROPEAN JOURNAL OF BIOCHEMISTRY Fields, P. A., Wahlstrand, B. D., Somero, G. N. 2001; 268 (16): 4497-4505

  Abstract

  We examined the effects of temperature and stabilizing solutes on A4-lactate dehydrogenase (A4-LDH) from warm- and cold-adapted fishes, to determine how extrinsic stabilizers affect orthologs with different intrinsic stabilities. Conformational changes during substrate binding are rate-limiting for A4-LDH, thus stabilization due to intrinsic or extrinsic factors leads to decreased activity. A4-LDH from a warm-temperate goby (Gillichthys mirabilis), which has lower values for kcat and the Michaelis constant for pyruvate ( K m PYR), was intrinsically more stable than the orthologs of the cold-adapted Antarctic notothenioids Parachaenichthys charcoti and Chionodraco rastrospinosus, as shown by a higher apparent transition ('melting') temperature (Tm(APP)). We used four solutes, glycerol, sucrose, trimethylamine-N-oxide and poly(ethylene glycol) 8000, which stabilize proteins through different modes of preferential exclusion, to study temperature-solute interactions of the three orthologs. Changes in Tm(APP) were similar for all orthologs in each solute tested, but the catalytic rate of G. mirabilis A4-LDH was decreased most by solutes and increased most by temperature. In contrast, the K m PYR values of the Antarctic orthologs were more affected than that of the goby by both solutes and temperature. We conclude that (a) preferential exclusion of solutes functions within the native state of A4-LDH to favor conformational microstates with minimal surface area; (b) the varied effects of the different solutes on the kinetic properties are due to the interaction between this nonspecific stabilization and the differing intrinsic stabilities of the orthologs; (c) the catalytic rates of A4-LDH orthologs are equally affected by stabilizing solutes, if measurements are made at physiologically appropriate temperatures; and (d) global stability and localized flexibility of these A4-LDH orthologs may evolve independently.

  View details for Web of Science ID 000170467000014

  View details for PubMedID 11502210

• Hypoxia-induced gene expression profiling in the euryoxic fish Gillichthys mirabilis PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Gracey, A. Y., Troll, J. V., Somero, G. N. 2001; 98 (4): 1993-1998

  Abstract

  Hypoxia is important in both biomedical and environmental contexts and necessitates rapid adaptive changes in metabolic organization. Mammals, as air breathers, have a limited capacity to withstand sustained exposure to hypoxia. By contrast, some aquatic animals, such as certain fishes, are routinely exposed and resistant to severe environmental hypoxia. Understanding the changes in gene expression in fishes exposed to hypoxic stress could reveal novel mechanisms of tolerance that may shed new light on hypoxia and ischemia in higher vertebrates. Using cDNA microarrays, we have studied gene expression in a hypoxia-tolerant burrow-dwelling goby fish, Gillichthys mirabilis. We show that a coherent picture of a complex transcriptional response can be generated for a nonmodel organism for which sequence data were unavailable. We demonstrate that: (i) although certain shifts in gene expression mirror changes in mammals, novel genes are differentially expressed in fish; and (ii) tissue-specific patterns of expression reflect the different metabolic roles of tissues during hypoxia.

  View details for Web of Science ID 000166949200121

  View details for PubMedID 11172064

  View details for PubMedCentralID PMC29370

• A comparative analysis of the evolutionary patterning and mechanistic bases of lactate dehydrogenase thermal stability in porcelain crabs, genus Petrolisthes JOURNAL OF EXPERIMENTAL BIOLOGY Stillman, J. H., Somero, G. N. 2001; 204 (4): 767-776

  Abstract

  The kinetic properties of orthologous homologs (orthologs) of enzymes are typically correlated with environmental temperatures in species adapted to different thermal regimes, but correlations between adaptation temperature and enzyme thermal stability are less clear. Although the thermal stability of a protein is related chiefly to its primary structure (including post-translational modification), thermal stability can also be altered by extrinsic factors present in the intracellular milieu. Here, we present a comparative analysis of the thermal stability of lactate dehydrogenase (LDH) orthologs from 22 congeneric species of porcelain crab (genera Petrolisthes and Allopetrolisthes) from a broad range of thermal habitats. Interspecific diversity of LDH stability is high: temperatures required for a 50 % loss of activity in 10 min ranged from 65 to 75.5 degrees C, corresponding to half-lives of less than 1 min to more than 3 h at 70 degrees C. Although stability is positively correlated with maximal habitat temperature in some sister taxa, phylogenetic comparative analysis incorporating all 22 species does not indicate that the interspecific diversity of LDH stability represents an adaptive response to current thermal habitats. Examination of the mechanistic bases of LDH stabilization indicates that differences in stability are related both to properties of the LDH molecule itself (intrinsic stability) and to the effects of extrinsic protein(s). Intrinsic differences were shown by the unfolding of structure during heating, as measured by circular dichroism spectroscopy. Stabilizing effects of extrinsic proteins are implied by the results of cellular fractionation experiments that removed low-molecular-mass solutes and proteins from the muscle homogenates. We conclude that the overall structural stability and functional properties of proteins can evolve independently and that in vivo protein-protein interactions can provide another means to regulate protein stability selectively.

  View details for Web of Science ID 000167441000016

  View details for PubMedID 11171359

• Heat-shock protein expression is absent in the Antarctic fish Trematomus bernacchii (family Nototheniidae) JOURNAL OF EXPERIMENTAL BIOLOGY Hofmann, G. E., Buckley, B. A., Airaksinen, S., Keen, J. E., Somero, G. N. 2000; 203 (15): 2331-2339

  Abstract

  The heat-shock response, the enhanced expression of one or more classes of molecular chaperones termed heat-shock proteins (hsps) in response to stress induced by high temperatures, is commonly viewed as a 'universal' characteristic of organisms. We examined the occurrence of the heat-shock response in a highly cold-adapted, stenothermal Antarctic teleost fish, Trematomus bernacchii, to determine whether this response has persisted in a lineage that has encountered very low and stable temperatures for at least the past 14-25 million years. The patterns of protein synthesis observed in in vivo metabolic labelling experiments that involved injection of (35)S-labelled methionine and cysteine into whole fish previously subjected to a heat stress of 10 degrees C yielded no evidence for synthesis of any size class of heat-shock protein. Parallel in vivo labelling experiments with isolated hepatocytes similarly showed significant amounts of protein synthesis, but no indication of enhanced expression of any class of hsp. The heavy metal cadmium, which is known to induce synthesis of hsps, also failed to alter the pattern of proteins synthesized in hepatocytes. Although stress-induced chaperones could not be detected under any of the experimental condition used, solid-phase antibody (western) analysis revealed that a constitutively expressed 70 kDa chaperone was present in this species, as predicted on the basis of requirements for chaperoning during protein synthesis. Amounts of the constitutively expressed 70 kDa chaperone increased in brain, but not in gill, during 22 days of acclimation to 5 degrees C. The apparent absence of a heat-shock response in this highly stenothermal species is interpreted as an indication that a physiological capacity observed in almost all other organisms has been lost as a result of the absence of positive selection during evolution at stable sub-zero temperatures. Whether the loss of the heat-shock response is due to dysfunctional genes for inducible hsps (loss of open reading frames or functional regulatory regions), unstable messenger RNAs, the absence of a functional heat-shock factor or some other lesion remains to be determined.

  View details for Web of Science ID 000088829800008

  View details for PubMedID 10887071

• Time course and magnitude of synthesis of heat-shock proteins in congeneric marine snails (Genus Tegula) from different tidal heights PHYSIOLOGICAL AND BIOCHEMICAL ZOOLOGY Tomanek, L., Somero, G. N. 2000; 73 (2): 249-256

  Abstract

  The time course and magnitude of the heat-shock response in relation to severity of thermal stress are important, yet poorly understood, aspects of thermotolerance. We examined patterns of protein synthesis in congeneric marine snails (genus Tegula) that occur at different heights along the subtidal to intertidal gradient after a thermal exposure (30 degrees C for 2.5 h, followed by 50 h recovery at 13 degrees C) that induced the heat-shock response. We monitored the kinetics and magnitudes of protein synthesis by quantifying incorporation of 35S-labeled methionine and cysteine into newly synthesized proteins and observed synthesis of putative heat-shock proteins (hsp's) of size classes 90, 77, 70, and 38 kDa. In the low- to mid-intertidal species, Tegula funebralis, whose body temperature frequently exceeds 30 degrees C during emersion, synthesis of hsp's commenced immediately after heat stress, reached maximal levels 1-3 h into recovery, and returned to prestress levels by 6 h, except for hsp90 (14 h). In contrast, in the low-intertidal to subtidal species, Tegula brunnea, for which 2.5 h at 30 degrees C represents a near lethal heat stress, synthesis of hsp's commenced 2-14 h after heat stress; reached maximal levels after 15-30 h, which exceeded magnitudes of synthesis in T. funebralis; and returned to prestress levels in the case of hsp90 (50 h) and hsp77 (30 h) but not in the case of hsp70 and hsp38. Exposures to 30 degrees C under aerial (emersion) and aquatic (immersion) conditions resulted in differences in hsp synthesis in T. brunnea but not in T. funebralis. The different time courses and magnitudes of hsp synthesis in these congeners suggest that the vertical limits of their distributions may be set in part by thermal stress.

  View details for Web of Science ID 000087276400013

  View details for PubMedID 10801403

• A comparative analysis of the upper thermal tolerance limits of eastern Pacific porcelain crabs, genus Petrolisthes: Influences of latitude, vertical zonation, acclimation, and phylogeny PHYSIOLOGICAL AND BIOCHEMICAL ZOOLOGY Stillman, J. H., Somero, G. N. 2000; 73 (2): 200-208

  Abstract

  Marine intertidal organisms are subjected to a variety of abiotic stresses, including aerial exposure and wide ranges of temperature. Intertidal species generally have higher thermal tolerance limits than do subtidal species, and tropical species have higher thermal tolerance limits than do temperate species. The adaptive significance of upper thermal tolerance limits of intertidal organisms, however, has not been examined within a comparative context. Here, we present a comparative analysis of the adaptive significance of upper thermal tolerance limits in 20 congeneric species of porcelain crabs, genus Petrolisthes, from intertidal and subtidal habitats throughout the eastern Pacific. Upper thermal tolerance limits are positively correlated with surface water temperatures and with maximal microhabitat temperatures. Analysis of phylogenetically independent contrasts (from a phylogenetic tree on the basis of the 16s rDNA gene sequence) suggests that upper thermal tolerance limits have evolved in response to maximal microhabitat temperatures. Upper thermal tolerance limits increased during thermal acclimation at elevated temperatures, the amount of increase being greater for subtidal than for intertidal species. This result suggests that the upper thermal tolerance limits of some intertidal species may be near current habitat temperature maxima, and global warming thus may affect the distribution limits of intertidal species to a greater extent than for subtidal species.

  View details for Web of Science ID 000087276400008

  View details for PubMedID 10801398

• Unity in diversity: A perspective on the methods, contributions, and future of comparative physiology ANNUAL REVIEW OF PHYSIOLOGY Somero, G. N. 2000; 62: 927-937

  View details for Web of Science ID 000088589000037

  View details for PubMedID 10845117

• Evolutionary and acclimation-induced variation in the heat-shock responses of congeneric marine snails (genus Tegula) from different thermal habitats: Implications for limits of thermotolerance and biogeography JOURNAL OF EXPERIMENTAL BIOLOGY Tomanek, L., Somero, G. N. 1999; 202 (21): 2925-2936

  View details for Web of Science ID 000083943500004

• The effect of temperature on fish keratocyte motility. Ream, R. A., Theriot, J. A., Somero, G. N. AMER SOC CELL BIOLOGY. 1999: 380A

  View details for Web of Science ID 000083673502197

• Evolutionary and acclimation-induced variation in the heat-shock responses of congeneric marine snails (genus Tegula) from different thermal habitats: implications for limits of thermotolerance and biogeography. The Journal of experimental biology Tomanek, L., Somero, G. N. 1999; 202 (Pt 21): 2925-2936

  Abstract

  Heat stress sufficient to cause cellular damage triggers the heat-shock response, the enhanced expression of a group of molecular chaperones called heat-shock proteins (hsps). We compared the heat-shock responses of four species of marine snails of the genus Tegula that occupy thermal niches differing in absolute temperature and range of temperature. We examined the effects of short-term heat stress and thermal acclimation on the synthesis of hsps of size classes 90, 77, 70 and 38 kDa by measuring incorporation of (35)S-labeled methionine and cysteine into newly synthesized proteins in gill tissue. Temperatures at which enhanced synthesis of hsps first occurred (T(on)), temperatures of maximal induction of hsp synthesis (T(peak)) and temperatures at which hsp synthesis was heat-inactivated (T(off)) were lowest in two low-intertidal to subtidal species from the temperate zone, T. brunnea and T. montereyi, intermediate in a mid- to low-intertidal species of the temperate zone, T. funebralis, and highest in a subtropical intertidal species from the Gulf of California, T. rugosa. Synthesis of hsps and other classes of protein by T. brunnea and T. montereyi was heat-inactivated at temperatures commonly encountered by T. funebralis during low tides on warm days. In turn, protein synthesis by T. funebralis was blocked at the upper temperatures of the habitat of T. rugosa. Acclimation of snails to 13 degrees C, 18 degrees C and 23 degrees C shifted T(on) and T(peak) for certain hsps, but did not affect T(off). The heat-shock responses of field-acclimatized snails were generally reduced in comparison with those of laboratory-acclimated snails. Overall, despite the occurrence of acclimatory plasticity in their heat-shock responses, genetically fixed differences in T(on), T(peak) and T(off) appear to exist that reflect the separate evolutionary histories of these species and may play important roles in setting their thermal tolerance limits and, thereby, their biogeographic distribution patterns.

  View details for PubMedID 10518474

• An optical oxygen sensor and reaction vessel for high-pressure applications LIMNOLOGY AND OCEANOGRAPHY Stokes, M. D., Somero, G. N. 1999; 44 (1): 189-195

  View details for Web of Science ID 000078378300017

• Hot spots in cold adaptation: Localized increases in conformational flexibility in lactate dehydrogenase A(4) orthologs of Antarctic notothenioid fishes PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Fields, P. A., Somero, G. N. 1998; 95 (19): 11476-11481

  Abstract

  To elucidate mechanisms of enzymatic adaptation to extreme cold, we determined kinetic properties, thermal stabilities, and deduced amino acid sequences of lactate dehydrogenase A4 (A4-LDH) from nine Antarctic (-1.86 to 1 degree C) and three South American (4 to 10 degree C) notothenioid teleosts. Higher Michaelis-Menten constants (Km) and catalytic rate constants (kcat) distinguish orthologs of Antarctic from those of South American species, but no relationship exists between adaptation temperature and the rate at which activity is lost because of heat denaturation. In all species, active site residues are conserved fully, and differences in kcat and Km are caused by substitutions elsewhere in the molecule. Within geographic groups, identical kinetic properties are generated by different substitutions. By combining our data with A4-LDH sequences for other vertebrates and information on roles played by localized conformational changes in setting kcat, we conclude that notothenioid A4-LDHs have adapted to cold temperatures by increases in flexibility in small areas of the molecule that affect the mobility of adjacent active-site structures. Using these findings, we propose a model that explains linked temperature-adaptive variation in Km and kcat. Changes in sequence that increase flexibility of regions of the enzyme involved in catalytic conformational changes may reduce energy (enthalpy) barriers to these rate-governing shifts in conformation and, thereby, increase kcat. However, at a common temperature of measurement, the higher configurational entropy of a cold-adapted enzyme may foster conformations that bind ligands poorly, leading to high Km values relative to warm-adapted orthologs.

  View details for Web of Science ID 000075957100085

  View details for PubMedID 9736762

  View details for PubMedCentralID PMC21668

• Effects of temperature on mitochondrial function in the Antarctic fish Trematomus bernacchii JOURNAL OF COMPARATIVE PHYSIOLOGY B-BIOCHEMICAL SYSTEMIC AND ENVIRONMENTAL PHYSIOLOGY Weinstein, R. B., Somero, G. N. 1998; 168 (3): 190-196

  View details for Web of Science ID 000073264300006

• Amino acid sequence differences cannot fully explain interspecific variation in thermal sensitivities of gobiid fish A(4)-lactate dehydrogenases (A(4)-LDHS) JOURNAL OF EXPERIMENTAL BIOLOGY Fields, P. A., Somero, G. N. 1997; 200 (13): 1839-1850

  View details for Web of Science ID A1997XK16200002

• Evolution of lactate dehydrogenase-A homologs of barracuda fishes (genus Sphyraena) from different thermal environments: Differences in kinetic properties and thermal stability are due to amino acid substitutions outside the active site BIOCHEMISTRY Holland, L. Z., McFallngai, M., Somero, G. N. 1997; 36 (11): 3207-3215

  Abstract

  Orthologous homologs of lactate dehydrogenase-A (LDH-A) (EC 1.1.1.27; NAD+:lactate oxidoreductase) of six barracuda species (genus Sphyraena) display differences in Michaelis-Menten constants (apparent Km) for substrate (pyruvate) and cofactor (NADH) that reflect evolution at different habitat temperatures. Significant increases in Km with increasing measurement temperature occur for all homologs, yet Km at normal body temperatures is similar among species because of the inverse relationship between adaptation temperature and Km. Thermal stabilities of the homologs also differ. To determine the amino acid substitutions responsible for differences in Km and thermal stability, peptide mapping of the LDH-As of all six species was first performed. Then, the amino acid sequences of the three homologs having the most similar peptide maps, those of the north temperate species, S. argentea, the subtropical species, S. lucasana, and the south temperate species, S. idiastes, were deduced from the respective cDNA sequences. At most, there were four amino acid substitutions between any pair of species, none of which occurred in the loop or substrate binding sites of the enzymes. The sequence of LDH-A from S. lucasana differs from that of S. idiastes only at position 8. The homolog of S. argentea differs from the other two sequences at positions 8, 61, 68, and 223. We used a full-length cDNA clone of LDH-A of S. lucasana to test, by site-directed mutagenesis, the importance of these sequence changes in establishing the observed differences in kinetics and thermal stability. Differences in sequence at sites 61 and/or 68 appear to account for the differences in Km between the LDH-As of S. argentea and S. lucasana. Differences at position 8 appear to account for the difference in thermal stability between the homologs of S. argentea and S. lucasana. Evolutionary adaptation of proteins to temperature thus may be achieved by minor changes in sequence at locations outside of active sites, and these changes may independently affect kinetic properties and thermal stabilities.

  View details for Web of Science ID A1997WN88600021

  View details for PubMedID 9115998

• Activity of lactate dehydrogenase but not its concentration of messenger RNA increases with body size in barred sand bass, Paralabrax nebulifer (Teleostei) BIOLOGICAL BULLETIN Yang, T. H., Somero, G. N. 1996; 191 (2): 155–58

  Abstract

  In white skeletal muscle of conspecific pelagic fishes, the activity of enzymes associated with anaerobic glycolysis, e.g., lactate dehydrogenase (LDH), usually scale positively with increasing body size; this pattern is opposite to that found for enzymes of aerobic metabolism, which decrease in mass-specific activity with size (1-3). The higher mass-specific capacities for anaerobic ATP generation in larger conspecifics are thought to facilitate conservation of high-speed ("burst") swimming ability in fishes of different sizes (1). To investigate the mechanisms responsible for scaling of LDH activity, total RNA, and the specific mRNA for LDH-A (the skeletal muscle isoform of the enzyme) in white muscle of paralabrax nebulifer, the barred sand bass. We also measured total protein concentration and the concentration of actin, the major protein of thin filaments, and its specific mRNA. Although LDH activity scaled significantly with body size as predicted (1-4), no other biochemical trait measured showed a significant size-dependent concentration. We conclude that the regulation of LDH activity in white muscle of this species is not governed by LDH-A mRNA concentrations, but rather by one or more other mechanisms, for example rate of translation of LDH message or a reduced rate of degradation of LDH-A in larger fish.

  View details for DOI 10.2307/1542918

  View details for Web of Science ID A1996VQ71700003

  View details for PubMedID 8916541

• Serge Timasheff: The man with a genius for solutions in biology BIOPHYSICAL JOURNAL Schellman, J. A., Somero, G. N. 1996; 71 (4): 1985–93

  View details for DOI 10.1016/S0006-3495(96)79396-7

  View details for Web of Science ID A1996VK29500029

  View details for PubMedID 8889172

  View details for PubMedCentralID PMC1233664

• Protein ubiquitination and stress protein synthesis in Mytilus trossulus occurs during recovery from tidal emersion MOLECULAR MARINE BIOLOGY AND BIOTECHNOLOGY Hofmann, G. E., Somero, G. N. 1996; 5 (3): 175–84

  View details for Web of Science ID A1996VG84900002

• Adaptation to temperature stress and aerial exposure in congeneric species of intertidal porcelain crabs (genus Petrolisthes): Correlation of physiology, biochemistry and morphology with vertical distribution JOURNAL OF EXPERIMENTAL BIOLOGY Stillman, J. H., Somero, G. N. 1996; 199 (8): 1845–55

  View details for Web of Science ID A1996VB86800022

• Fasting reduces protein and messenger RNA concentrations for lactate dehydrogenase but not for actin in white muscle of scorpionfish (Scorpaena guttata, Teleostei) MOLECULAR MARINE BIOLOGY AND BIOTECHNOLOGY Yang, T. H., Somero, G. N. 1996; 5 (2): 153–61

  View details for Web of Science ID A1996UN48800008

• Temperature and proteins: Little things can mean a lot NEWS IN PHYSIOLOGICAL SCIENCES Somero, G. N. 1996; 11: 72-77

  View details for Web of Science ID A1996UG16000004

• TEMPERATURE TOLERANCE OF SOME ANTARCTIC FISHES SCIENCE SOMERO, G. N., DEVRIES, A. L. 1967; 156 (3772): 257-&

  Abstract

  Three species of Antarctic fishes which live in constantly near-freezing waters have a markedly low upper-lethal temperature of 6 degrees C ; this is the lowest upper-lethal temperature reported for any organism. The fishes survive supercooling to -2.5 degrees C. Data on brain metabolism in vitro support the hypothesis that the central nervous system is a primary site of thermal injury.

  View details for DOI 10.1126/science.156.3772.257

  View details for Web of Science ID A19679159700031

  View details for PubMedID 6021046