Kelsie Elizabeth Hunnicutt

All Publications

• A tsunami of genome reshuffling. Nature ecology & evolution Hunnicutt, K. E. 2026

  View details for DOI 10.1038/s41559-026-03168-1

  View details for PubMedID 42791312

• Two melanic pigment patterns are associated with a sex chromosome-linked oncogene in the mountain swordtail Xiphophorus nezahualcoyotl. bioRxiv : the preprint server for biology Given, L. A., Gozashti, L., Baczenas, J. J., Sood, R., Haghani, N. B., Hunnicutt, K. E., Gunn, T. R., Preising, G. A., Sudmant, P. H., Powell, D. L., Dodge, T. O., Schumer, M. 2026

  Abstract

  Sex-linked traits are widespread, but their genetic architecture has been challenging to characterize, due in part to the repetitive and structurally complex nature of sex chromosomes. In swordtails and platyfish of the genus Xiphophorus, diverse melanic pigmentation patterns are thought to be controlled by a region on the sex chromosomes classically referred to as the "macromelanophore determining locus". Despite nearly a century of study, the identity of the causal gene remains controversial, partially due to previous inability to fully sequence the sex chromosomes. Here, we characterize and investigate two melanin-based pigmentation phenotypes in the species X. nezahualcoyotl: "spotted side" and "marmoratus". We generate a gapless near-telomere-to-telomere X. nezahualcoyotl assembly and perform GWAS to identify regions associated with pigmentation pattern variation and sex-determination. We find both patterns map near the sex-determining region and to a narrow interval near the oncogene xmrk. By generating additional long-read assemblies of sex chromosomes derived from individuals with distinct phenotypes, we find haplotypes containing xmrk can be both X- and Y-linked, and vary dramatically in gene content, structure, and accumulation of repetitive elements including a newly described composite satellite. This variability may impact the region's stability and affect recombination between haplotypes associated with each pattern. Our results shed light on a longstanding debate surrounding the genetic architecture of sex-linked phenotypes. More generally, we showcase how long-read sequencing can reveal phenotypic variation linked to complex and dynamic genomic regions, which may contribute to the evolution of diverse sex-linked traits.

  View details for DOI 10.64898/2026.06.08.730778

  View details for PubMedID 42327189

  View details for PubMedCentralID PMC13277934

• Genetic Diversity and Population Structure of the Black-Footed Cat: Insights into Felis's Deadliest Predator. bioRxiv : the preprint server for biology Grant, V. B., Hunnicutt, K., Schroeder, M., Küsters, M., Oppenheimer, J., Banerjee, S., Baczenas, J. J., Petrov, D., Bishop, J. M., Lamberski, N., Wilson, B., Sliwa, A., Shapiro, B., Solari, K. A., Aguillón, S. M., Armstrong, E. E., Schumer, M. 2026

  Abstract

  Black-footed cats (Felis nigripes) are one of Africa's least studied felines. The population dynamics and demographic history of this solitary species have not been well-described. Reports of ongoing decline of present-day populations resulted in the IUCN Red List categorizing the species as vulnerable to extinction. As populations decline and become isolated from each other, they become susceptible to strong genetic drift and inbreeding, which can lead to the accumulation of deleterious alleles and increased extinction risk. However, the IUCN cited data deficiencies across the species range as a limitation in this categorization for black-footed cats. In cases where ecological surveys are lacking, range-wide population genomic surveys can improve our understanding of population dynamics.In the first genomic study of free-roaming individuals, we sequenced whole genomes of black-footed cats (N=44) from across their distribution. To do so, we incorporated whole genome sequences generated from both modern biological samples and century-old museum specimens. We assembled a highly contiguous reference genome using a combination of PacBio HiFi data and publicly available Hi-C data and investigated the demographic history, population structure, and genetic diversity of wild black-footed cats. We found evidence of historical effective population sizes of ~11,500 individuals, which is lower than estimates reported in other felid species. Consistent with modest historical population sizes, we found that present-day genome-wide diversity was low (π ≈ 0.0004). However, despite low genetic diversity, we find that black-footed cat genomes do not harbor long runs of homozygosity. Simulation results indicate that low present-day genetic diversity may simply result from modest historical population size. However, other analyses point to evidence of a population contraction in the last 50 generations, which could contribute to future genomic erosion. We also compared genomic variation in populations across the range to evaluate patterns of population structure, finding evidence of higher genetic similarity between individuals in closer geographic proximity.Overall, these results provide range-wide information about the demographic history and present-day genetic diversity of an understudied species. Together with analyses of population structure, we speculate that there may be greater connectivity between populations of black-footed cats than previously assumed. Our study underscores the utility of genomic data in providing insights into population dynamics for better conservation management.

  View details for DOI 10.64898/2026.05.29.728895

  View details for PubMedID 42282534

  View details for PubMedCentralID PMC13251930

• Insertion of an invading retrovirus regulates a novel color trait in swordtail fish. bioRxiv : the preprint server for biology Haghani, N. B., Dodge, T. O., Baczenas, J. J., Gunn, T. R., He, Q., Pangburn, W., Sood, R., Fascinetto-Zago, P., Du, K., Kaatmann, A., Ou, Z., Dougan, S., Yang, T. T., Olmos-Santiago, N. S., Preising, G. A., Payne, C. Y., Cox, S. K., Hunnicutt, K. E., Madrzyk, M., Moran, B., Stigloher, C., Powell, D. L., Schartl, M., Gifford, C. A., Han, G. Z., Schumer, M. 2025

  Abstract

  For over a century, evolutionary biologists have been motivated to understand the mechanisms through which organisms adapt to their environments. Coloration and pigmentation are remarkably variable within and between species and can serve as an important window into the mechanisms of adaptation. Here, we map the genetic basis of a newly described iridescence trait in swordtail fish to a single locus. Individuals with this trait appear to sparkle as they move through the water. We find that the trait is driven by the recent endogenization of a retrovirus that inserted near the gene alkal2a. This insertion is associated with changes in the chromatin landscape, upregulation of alkal2a, and accumulation of iridescent cells that adhere to the scales. Rather than causing diseases, our results demonstrate that invading endogenous retroviruses can also regulate novel trait variation in the host. Moreover, we find that this coloration trait may act as an important signal in interactions between fish and their predators in the natural environment.

  View details for DOI 10.1101/2025.11.07.687308

  View details for PubMedID 41292848

  View details for PubMedCentralID PMC12642411

• Different complex regulatory phenotypes underlie hybrid male sterility in divergent rodent crosses GENETICS Hunnicutt, K. E., Callahan, C. M., Keeble, S., Moore, E. C., Good, J. M., Larson, E. L. 2024; 229 (2)

  Abstract

  Hybrid incompatibilities are a critical component of species barriers and may arise due to negative interactions between divergent regulatory elements in parental species. We used a comparative approach to identify common themes in the regulatory phenotypes associated with hybrid male sterility in two divergent rodent crosses, dwarf hamsters and house mice. We investigated three potential characteristic gene expression phenotypes in hybrids including the propensity of transgressive differentially expressed genes toward over or underexpression, the influence of developmental stage on patterns of misexpression, and the role of the sex chromosomes on misexpression phenotypes. In contrast to near pervasive overexpression in hybrid house mice, we found that misexpression in hybrid dwarf hamsters was dependent on developmental stage. In both house mouse and dwarf hamster hybrids, however, misexpression increased with the progression of spermatogenesis, although to varying extents and with potentially different consequences. In both systems, we detected sex chromosome-specific overexpression in stages of spermatogenesis where inactivated X chromosome expression was expected, but the hybrid overexpression phenotypes were fundamentally different. Importantly, misexpression phenotypes support the presence of multiple developmental blocks to spermatogenesis in dwarf hamster hybrids, including a potential role of meiotic stalling or breakdown early in spermatogenesis. Collectively, we demonstrate that while there are some similarities in hybrid expression phenotypes of house mice and dwarf hamsters, there are also clear differences that point toward unique mechanisms underlying hybrid male sterility. Our results highlight the potential of comparative approaches in helping to understand the causes and consequences of disrupted gene expression in speciation.

  View details for DOI 10.1093/genetics/iyae198

  View details for Web of Science ID 001379219100001

  View details for PubMedID 39601270

  View details for PubMedCentralID PMC11796465

• Genetic divergence among threespine stickleback that differ in nuptial coloration JOURNAL OF EVOLUTIONARY BIOLOGY Jenck, C. S., Lehto, W. R., Hunnicutt, K. E., Murphy, S. M., Quinn, T. W., Larson, E. L., Tinghitella, R. M. 2022; 35 (7): 934-947

  Abstract

  Sexual signals are shaped by their intended and unintended receivers as well as the signalling environment. This interplay between sexual and natural selection can lead to divergence in signals in heterogeneous environments. Yet, the extent to which gene flow is restricted when signalling phenotypes vary across environments and over what spatial scales remains an outstanding question. In this study, we quantify gene flow between two colour morphs, red and black, of freshwater threespine stickleback fish (Gasterosteus aculeatus). We capitalize on the very recent divergence of signalling phenotypes in this system to characterize within-species and among-morph genetic variation and to test for levels of gene flow between colour morphs in Oregon and Washington. Despite limited evidence for assortative mating between allopatric red and black populations, we found that black populations are genetically distinct from nearby red populations and that the black morph appears to have evolved independently at least twice in Oregon and Washington. Surprisingly, we uncovered a group of stickleback in one small coastal stream, Connor Creek, which is genetically and morphologically distinct from the red and black colour morphs and from marine stickleback. Historically, both colour morphs have coexisted in this location and sometimes hybridized, raising new questions about the origins and history of these fish, which were first described as anadromous-black hybrids >50 years ago. Understanding how genetic variation is currently partitioned within and among populations and colour morphs in this system should prompt future studies to assess the relative roles of habitat, ecological and pre- and post-reproductive barriers in the genetic divergence and phenotypic patterns we observe in nature.

  View details for DOI 10.1111/jeb.14035

  View details for Web of Science ID 000812587200001

  View details for PubMedID 35716364

• The Evolution of Widespread Recombination Suppression on the Dwarf Hamster (<i>Phodopus</i>) X Chromosome GENOME BIOLOGY AND EVOLUTION Moore, E. C., Thomas, G. W. C., Mortimer, S., Kopania, E. E. K., Hunnicutt, K. E., Clare-Salzler, Z. J., Larson, E. L., Good, J. M. 2022; 14 (6)

  Abstract

  The X chromosome of therian mammals shows strong conservation among distantly related species, limiting insights into the distinct selective processes that have shaped sex chromosome evolution. We constructed a chromosome-scale de novo genome assembly for the Siberian dwarf hamster (Phodopus sungorus), a species reported to show extensive recombination suppression across an entire arm of the X chromosome. Combining a physical genome assembly based on shotgun and long-range proximity ligation sequencing with a dense genetic map, we detected widespread suppression of female recombination across ∼65% of the Phodopus X chromosome. This region of suppressed recombination likely corresponds to the Xp arm, which has previously been shown to be highly heterochromatic. Using additional sequencing data from two closely related species (P. campbelli and P. roborovskii), we show that recombination suppression on Xp appears to be independent of major structural rearrangements. The suppressed Xp arm was enriched for several transposable element families and de-enriched for genes primarily expressed in placenta, but otherwise showed similar gene densities, expression patterns, and rates of molecular evolution when compared to the recombinant Xq arm. Phodopus Xp gene content and order was also broadly conserved relative to the more distantly related rat X chromosome. These data suggest that widespread suppression of recombination has likely evolved through the transient induction of facultative heterochromatin on the Phodopus Xp arm without major changes in chromosome structure or genetic content. Thus, substantial changes in the recombination landscape have so far had relatively subtle influences on patterns of X-linked molecular evolution in these species.

  View details for DOI 10.1093/gbe/evac080

  View details for Web of Science ID 000809211800001

  View details for PubMedID 35642315

  View details for PubMedCentralID PMC9185382

• Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids (vol 12, jkab407, 2022) G3-GENES GENOMES GENETICS Larson, E. L., Kopania, E. E. K., Hunnicutt, K. E., Vanderpool, D., Keeble, S., Good, J. M. 2022; 12 (3)

  View details for DOI 10.1093/g3journal/jkac007

  View details for Web of Science ID 000776673300026

• Unraveling patterns of disrupted gene expression across a complex tissue EVOLUTION Hunnicutt, K. E., Good, J. M., Larson, E. L. 2022; 76 (2): 275-291

  Abstract

  Whole tissue RNASeq is the standard approach for studying gene expression divergence in evolutionary biology and provides a snapshot of the comprehensive transcriptome for a given tissue. However, whole tissues consist of diverse cell types differing in expression profiles, and the cellular composition of these tissues can evolve across species. Here, we investigate the effects of different cellular composition on whole tissue expression profiles. We compared gene expression from whole testes and enriched spermatogenesis populations in two species of house mice, Mus musculus musculus and M. m. domesticus, and their sterile and fertile F1 hybrids, which differ in both cellular composition and regulatory dynamics. We found that cellular composition differences skewed expression profiles and differential gene expression in whole testes samples. Importantly, both approaches were able to detect large-scale patterns such as disrupted X chromosome expression, although whole testes sampling resulted in decreased power to detect differentially expressed genes. We encourage researchers to account for histology in RNASeq and consider methods that reduce sample complexity whenever feasible. Ultimately, we show that differences in cellular composition between tissues can modify expression profiles, potentially altering inferred gene ontological processes, insights into gene network evolution, and processes governing gene expression evolution.

  View details for DOI 10.1111/evo.14420

  View details for Web of Science ID 000740055300001

  View details for PubMedID 34882778

  View details for PubMedCentralID PMC9355168

• Stage-specific disruption of X chromosome expression during spermatogenesis in sterile house mouse hybrids G3-GENES GENOMES GENETICS Larson, E. L., Kopania, E. E. K., Hunnicutt, K. E., Vanderpool, D., Keeble, S., Good, J. M. 2022; 12 (2)

  Abstract

  Hybrid sterility is a complex phenotype that can result from the breakdown of spermatogenesis at multiple developmental stages. Here, we disentangle two proposed hybrid male sterility mechanisms in the house mice, Mus musculus domesticus and M. m. musculus, by comparing patterns of gene expression in sterile F1 hybrids from a reciprocal cross. We found that hybrid males from both cross directions showed disrupted X chromosome expression during prophase of meiosis I consistent with a loss of meiotic sex chromosome inactivation (MSCI) and Prdm9-associated sterility, but that the degree of disruption was greater in mice with an M. m. musculus X chromosome consistent with previous studies. During postmeiotic development, gene expression on the X chromosome was only disrupted in one cross direction, suggesting that misexpression at this later stage was genotype-specific and not a simple downstream consequence of MSCI disruption which was observed in both reciprocal crosses. Instead, disrupted postmeiotic expression may depend on the magnitude of earlier disrupted MSCI, or the disruption of particular X-linked genes or gene networks. Alternatively, only hybrids with a potential deficit of Sly copies, a Y-linked ampliconic gene family, showed overexpression in postmeiotic cells, consistent with a previously proposed model of antagonistic coevolution between the X- and Y-linked ampliconic genes contributing to disrupted expression late in spermatogenesis. The relative contributions of these two regulatory mechanisms and their impact on sterility phenotypes await further study. Our results further support the hypothesis that X-linked hybrid sterility in house mice has a variable genetic basis, and that genotype-specific disruption of gene regulation contributes to overexpression of the X chromosome at different stages of development. Overall, these findings underscore the critical role of epigenetic regulation of the X chromosome during spermatogenesis and suggest that these processes are prone to disruption in hybrids.

  View details for DOI 10.1093/g3journal/jkab407

  View details for Web of Science ID 000768242900014

  View details for PubMedID 34864964

  View details for PubMedCentralID PMC9210296

• Pedigree-based and phylogenetic methods support surprising patterns of mutation rate and spectrum in the gray mouse lemur HEREDITY Campbell, C., Tiley, G. P., Poelstra, J. W., Hunnicutt, K. E., Larsen, P. A., Lee, H., Thorne, J. L., dos Reis, M., Yoder, A. D. 2021; 127 (2): 233-244

  Abstract

  Mutations are the raw material on which evolution acts, and knowledge of their frequency and genomic distribution is crucial for understanding how evolution operates at both long and short timescales. At present, the rate and spectrum of de novo mutations have been directly characterized in relatively few lineages. Our study provides the first direct mutation-rate estimate for a strepsirrhine (i.e., the lemurs and lorises), which comprises nearly half of the primate clade. Using high-coverage linked-read sequencing for a focal quartet of gray mouse lemurs (Microcebus murinus), we estimated the mutation rate to be among the highest calculated for a mammal at 1.52 × 10-8 (95% credible interval: 1.28 × 10-8-1.78 × 10-8) mutations/site/generation. Further, we found an unexpectedly low count of paternal mutations, and only a modest overrepresentation of mutations at CpG sites. Despite the surprising nature of these results, we found both the rate and spectrum to be robust to the manipulation of a wide range of computational filtering criteria. We also sequenced a technical replicate to estimate a false-negative and false-positive rate for our data and show that any point estimate of a de novo mutation rate should be considered with a large degree of uncertainty. For validation, we conducted an independent analysis of context-dependent substitution types for gray mouse lemur and five additional primate species for which de novo mutation rates have also been estimated. These comparisons revealed general consistency of the mutation spectrum between the pedigree-based and the substitution-rate analyses for all species compared.

  View details for DOI 10.1038/s41437-021-00446-5

  View details for Web of Science ID 000673173700001

  View details for PubMedID 34272504

  View details for PubMedCentralID PMC8322134

• Streetlights positively affect the presence of an invasive grass species ECOLOGY AND EVOLUTION Murphy, S. M., Vyas, D. K., Hoffman, J. L., Jenck, C. S., Washburn, B. A., Hunnicutt, K. E., Davidson, A., Andersen, J. M., Bennet, R. K., Gifford, A., Herrera, M., Lawler, B., Lorman, S., Peacock, V., Walker, L., Watkins, E., Wilkinson, L., Williams, Z., Tinghitella, R. M. 2021; 11 (15): 10320-10326

  Abstract

  Anthropogenic disturbances associated with urban ecosystems can create favorable conditions for populations of some invasive plant species. Light pollution is one of these disturbances, but how it affects the growth and establishment of invasive plant populations is unknown. Cheatgrass (Bromus tectorum) is a problematic invasive species where it has displaced native grassland communities in the United States, but to our knowledge, there have been no studies of the ecological factors that affect cheatgrass presence in urban ecosystems. We conducted field surveys in urban alleys in Denver, Colorado, to compare the presence of cheatgrass at sites with and without artificial light at night (hereafter artificial light) from streetlights. These streetlights are mounted on utility poles, which cause ground disturbance when installed in alleys; we were able to test the independent effect of poles on cheatgrass establishment because not all poles have streetlights on them. We found that cheatgrass was positively associated with the presence of streetlights and to a lesser extent poles. In addition to cheatgrass, we also found that other plants were positively associated with the presence of both poles and streetlights. Our results suggest that artificial light may benefit the occurrence of cheatgrass and other plant species in urban settings. While invasive populations of cheatgrass in wild habitats attract the most attention from managers, we suggest more consideration for this grass in urban environments where its growth and establishment benefit from anthropogenic changes.

  View details for DOI 10.1002/ece3.7835

  View details for Web of Science ID 000671516700001

  View details for PubMedID 34367577

  View details for PubMedCentralID PMC8328438

• Cryptic Patterns of Speciation in Cryptic Primates: Microendemic Mouse Lemurs and the Multispecies Coalescent SYSTEMATIC BIOLOGY Poelstra, J. W., Salmona, J., Tiley, G. P., Schussler, D., Blanco, M. B., Andriambeloson, J. B., Bouchez, O., Campbell, C., Etter, P. D., Hohenlohe, P. A., Hunnicutt, K. E., Iribar, A., Johnson, E. A., Kappeler, P. M., Larsen, P. A., Manzi, S., Ralison, J. M., Randrianambinina, B., Rasoloarison, R. M., Rasolofoson, D. W., Stahlke, A. R., Weisrock, D. W., Williams, R. C., Chikhi, L., Louis Jr, E. E., Radespiel, U., Yoder, A. D. 2021; 70 (2): 203-218

  Abstract

  Mouse lemurs (Microcebus) are a radiation of morphologically cryptic primates distributed throughout Madagascar for which the number of recognized species has exploded in the past two decades. This taxonomic revision has prompted understandable concern that there has been substantial oversplitting in the mouse lemur clade. Here, we investigate mouse lemur diversity in a region in northeastern Madagascar with high levels of microendemism and predicted habitat loss. We analyzed RADseq data with multispecies coalescent (MSC) species delimitation methods for two pairs of sister lineages that include three named species and an undescribed lineage previously identified to have divergent mtDNA. Marked differences in effective population sizes, levels of gene flow, patterns of isolation-by-distance, and species delimitation results were found among the two pairs of lineages. Whereas all tests support the recognition of the presently undescribed lineage as a separate species, the species-level distinction of two previously described species, M. mittermeieri and M. lehilahytsara is not supported-a result that is particularly striking when using the genealogical discordance index (gdi). Nonsister lineages occur sympatrically in two of the localities sampled for this study, despite an estimated divergence time of less than 1 Ma. This suggests rapid evolution of reproductive isolation in the focal lineages and in the mouse lemur clade generally. The divergence time estimates reported here are based on the MSC calibrated with pedigree-based mutation rates and are considerably more recent than previously published fossil-calibrated relaxed-clock estimates. We discuss the possible explanations for this discrepancy, noting that there are theoretical justifications for preferring the MSC estimates in this case. [Cryptic species; effective population size; microendemism; multispecies coalescent; speciation; species delimitation.].

  View details for DOI 10.1093/sysbio/syaa053

  View details for Web of Science ID 000637328600001

  View details for PubMedID 32642760

• The beautiful chromosomes of shrews (Book Review) EVOLUTION Book Review Authored by: Larson, E. L., Hunnicutt, K. E. 2020; 74 (7): 1584-1586

  View details for DOI 10.1111/evo.14019

  View details for Web of Science ID 000535644900001

• Comparative Genomic Analysis of the Pheromone Receptor Class 1 Family (V1R) Reveals Extreme Complexity in Mouse Lemurs (Genus, <i>Microcebus</i>) and a Chromosomal Hotspot across Mammals GENOME BIOLOGY AND EVOLUTION Hunnicutt, K. E., Tiley, G. P., Williams, R. C., Larsen, P. A., Blanco, M. B., Rasoloarison, R. M., Campbell, C., Zhu, K., Weisrock, D. W., Matsunami, H., Yoder, A. D. 2020; 12 (1): 3562-3579

  Abstract

  Sensory gene families are of special interest for both what they can tell us about molecular evolution and what they imply as mediators of social communication. The vomeronasal type-1 receptors (V1Rs) have often been hypothesized as playing a fundamental role in driving or maintaining species boundaries given their likely function as mediators of intraspecific mate choice, particularly in nocturnal mammals. Here, we employ a comparative genomic approach for revealing patterns of V1R evolution within primates, with a special focus on the small-bodied nocturnal mouse and dwarf lemurs of Madagascar (genera Microcebus and Cheirogaleus, respectively). By doubling the existing genomic resources for strepsirrhine primates (i.e. the lemurs and lorises), we find that the highly speciose and morphologically cryptic mouse lemurs have experienced an elaborate proliferation of V1Rs that we argue is functionally related to their capacity for rapid lineage diversification. Contrary to a previous study that found equivalent degrees of V1R diversity in diurnal and nocturnal lemurs, our study finds a strong correlation between nocturnality and V1R elaboration, with nocturnal lemurs showing elaborate V1R repertoires and diurnal lemurs showing less diverse repertoires. Recognized subfamilies among V1Rs show unique signatures of diversifying positive selection, as might be expected if they have each evolved to respond to specific stimuli. Furthermore, a detailed syntenic comparison of mouse lemurs with mouse (genus Mus) and other mammalian outgroups shows that orthologous mammalian subfamilies, predicted to be of ancient origin, tend to cluster in a densely populated region across syntenic chromosomes that we refer to as a V1R "hotspot."

  View details for DOI 10.1093/gbe/evz200

  View details for Web of Science ID 000522860800003

  View details for PubMedID 31555816

  View details for PubMedCentralID PMC6944220

• Conservation genomic analysis reveals ancient introgression and declining levels of genetic diversity in Madagascar's hibernating dwarf lemurs HEREDITY Williams, R. C., Blanco, M. B., Poelstra, J. W., Hunnicutt, K. E., Comeault, A. A., Yoder, A. D. 2020; 124 (1): 236-251

  Abstract

  Madagascar's biodiversity is notoriously threatened by deforestation and climate change. Many of these organisms are rare, cryptic, and severely threatened, making population-level sampling unrealistic. Such is the case with Madagascar's dwarf lemurs (genus Cheirogaleus), the only obligate hibernating primate. We here apply comparative genomic approaches to generate the first genome-wide estimates of genetic diversity within dwarf lemurs. We generate a reference genome for the fat-tailed dwarf lemur, Cheirogaleus medius, and use this resource to facilitate analyses of high-coverage (~30×) genome sequences for wild-caught individuals representing species: C. sp. cf. medius, C. major, C. crossleyi, and C. sibreei. This study represents the largest contribution to date of novel genomic resources for Madagascar's lemurs. We find concordant phylogenetic relationships among the four lineages of Cheirogaleus across most of the genome, and yet detect a number of discordant genomic regions consistent with ancient admixture. We hypothesized that these regions could have resulted from adaptive introgression related to hibernation, indeed finding that genes associated with hibernation are present, though most significantly, that gene ontology categories relating to transcription are over-represented. We estimate levels of heterozygosity and find particularly low levels in an individual sampled from an isolated population of C. medius that we refer to as C. sp. cf. medius. Results are consistent with a recent decline in effective population size, which is evident across species. Our study highlights the power of comparative genomic analysis for identifying species and populations of conservation concern, as well as for illuminating possible mechanisms of adaptive phenotypic evolution.

  View details for DOI 10.1038/s41437-019-0260-9

  View details for Web of Science ID 000502333100019

  View details for PubMedID 31435007

  View details for PubMedCentralID PMC6906314

• Warning SINEs: <i>Alu</i> elements, evolution of the human brain, and the spectrum of neurological disease CHROMOSOME RESEARCH Larsen, P. A., Hunnicutt, K. E., Larsen, R. J., Yoder, A. D., Saunders, A. M. 2018; 26 (1-2): 93-111

  Abstract

  Alu elements are a highly successful family of primate-specific retrotransposons that have fundamentally shaped primate evolution, including the evolution of our own species. Alus play critical roles in the formation of neurological networks and the epigenetic regulation of biochemical processes throughout the central nervous system (CNS), and thus are hypothesized to have contributed to the origin of human cognition. Despite the benefits that Alus provide, deleterious Alu activity is associated with a number of neurological and neurodegenerative disorders. In particular, neurological networks are potentially vulnerable to the epigenetic dysregulation of Alu elements operating across the suite of nuclear-encoded mitochondrial genes that are critical for both mitochondrial and CNS function. Here, we highlight the beneficial neurological aspects of Alu elements as well as their potential to cause disease by disrupting key cellular processes across the CNS. We identify at least 37 neurological and neurodegenerative disorders wherein deleterious Alu activity has been implicated as a contributing factor for the manifestation of disease, and for many of these disorders, this activity is operating on genes that are essential for proper mitochondrial function. We conclude that the epigenetic dysregulation of Alu elements can ultimately disrupt mitochondrial homeostasis within the CNS. This mechanism is a plausible source for the incipient neuronal stress that is consistently observed across a spectrum of sporadic neurological and neurodegenerative disorders.

  View details for DOI 10.1007/s10577-018-9573-4

  View details for Web of Science ID 000427803400007

  View details for PubMedID 29460123

  View details for PubMedCentralID PMC5857278

• The <i>Alu</i> neurodegeneration hypothesis: A primate-specific mechanism for neuronal transcription noise, mitochondrial dysfunction, and manifestation of neurodegenerative disease ALZHEIMERS & DEMENTIA Larsen, P. A., Lutz, M. W., Hunnicutt, K. E., Mihovilovic, M., Saunders, A. M., Yoder, A. D., Roses, A. D. 2017; 13 (7): 828-838

  Abstract

  It is hypothesized that retrotransposons have played a fundamental role in primate evolution and that enhanced neurologic retrotransposon activity in humans may underlie the origin of higher cognitive function. As a potential consequence of this enhanced activity, it is likely that neurons are susceptible to deleterious retrotransposon pathways that can disrupt mitochondrial function. An example is observed in the TOMM40 gene, encoding a β-barrel protein critical for mitochondrial preprotein transport. Primate-specific Alu retrotransposons have repeatedly inserted into TOMM40 introns, and at least one variant associated with late-onset Alzheimer's disease originated from an Alu insertion event. We provide evidence of enriched Alu content in mitochondrial genes and postulate that Alus can disrupt mitochondrial populations in neurons, thereby setting the stage for progressive neurologic dysfunction. This Alu neurodegeneration hypothesis is compatible with decades of research and offers a plausible mechanism for the disruption of neuronal mitochondrial homeostasis, ultimately cascading into neurodegenerative disease.

  View details for DOI 10.1016/j.jalz.2017.01.017

  View details for Web of Science ID 000404559300011

  View details for PubMedID 28242298

  View details for PubMedCentralID PMC6647845

• Geogenetic patterns in mouse lemurs (genus <i>Microcebus</i>) reveal the ghosts of Madagascar's forests past PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Yoder, A. D., Campbell, C., Blanco, M. B., dos Reis, M., Ganzhorn, J. U., Goodman, S. M., Hunnicutt, K. E., Larsen, P. A., Kappeler, P. M., Rasoloarison, R. M., Ralison, J. M., Swofford, D. L., Weisrock, D. W. 2016; 113 (29): 8049-8056

  Abstract

  Phylogeographic analysis can be described as the study of the geological and climatological processes that have produced contemporary geographic distributions of populations and species. Here, we attempt to understand how the dynamic process of landscape change on Madagascar has shaped the distribution of a targeted clade of mouse lemurs (genus Microcebus) and, conversely, how phylogenetic and population genetic patterns in these small primates can reciprocally advance our understanding of Madagascar's prehuman environment. The degree to which human activity has impacted the natural plant communities of Madagascar is of critical and enduring interest. Today, the eastern rainforests are separated from the dry deciduous forests of the west by a large expanse of presumed anthropogenic grassland savanna, dominated by the Family Poaceae, that blankets most of the Central Highlands. Although there is firm consensus that anthropogenic activities have transformed the original vegetation through agricultural and pastoral practices, the degree to which closed-canopy forest extended from the east to the west remains debated. Phylogenetic and population genetic patterns in a five-species clade of mouse lemurs suggest that longitudinal dispersal across the island was readily achieved throughout the Pleistocene, apparently ending at ∼55 ka. By examining patterns of both inter- and intraspecific genetic diversity in mouse lemur species found in the eastern, western, and Central Highland zones, we conclude that the natural environment of the Central Highlands would have been mosaic, consisting of a matrix of wooded savanna that formed a transitional zone between the extremes of humid eastern and dry western forest types.

  View details for DOI 10.1073/pnas.1601081113

  View details for Web of Science ID 000380224500040

  View details for PubMedID 27432945

  View details for PubMedCentralID PMC4961119