Professor Lowe trained as a biologist in the UK at Sussex University. He moved to The USA for graduate training with Greg Wray at SUNY Stonybrook in the Department of Ecology and Evolution, where he worked on the evolution of body plans and the origin of the echinoderms. Following his PhD. he worked as a Miller Fellow at UC Berkeley working on the origin of chordates focussing on the evolution of the vertebrate central nervous system, first in Mike Levine's lab, then with John Gerhart and Marc Kirschner from Harvard. His first academic position was as an Assistant Professor in the Department of Organismal Biology and Anatomy at the University of Chicago in 2005. He moved to Stanford in 2010 and his lab is based at Hopkins Marine Station in Monterey.
Honors & Awards
Searle Scholars Fellow, Searle Scholars Program (2008-2011)
Miller Postdoctoral Fellowship, UC Berkeley (1998-2001)
BSc. Hons, University of Sussex, Biology with European Studies (1991)
PhD, Dept of Ecology and Evolution, SUNY Stony Brook, Ecology and Evolution (1998)
Current Research and Scholarly Interests
Evolution and development, specifically the evolution of the deuterostomes
BIO 136, BIO 236, GEOLSCI 136, GEOLSCI 236 (Win)
Independent Studies (9)
- Directed Instruction or Reading
BIOHOPK 198H (Aut, Win, Spr, Sum)
- Directed Reading in Biology
BIO 198 (Aut, Win, Spr, Sum)
- Out-of-Department Directed Reading
BIO 198X (Sum)
- Out-of-Department Undergraduate Research
BIO 199X (Sum)
BIOHOPK 300H (Aut, Win, Spr, Sum)
- Teaching Practicum in Biology
BIO 290 (Aut, Win, Spr)
- Teaching Practicum in Biology
BIOHOPK 290H (Win, Spr, Sum)
- Undergraduate Research
BIO 199 (Sum)
- Undergraduate Research
BIOHOPK 199H (Aut, Win, Spr, Sum)
- Directed Instruction or Reading
Prior Year Courses
- Developmental Biology in the Ocean: Comparative Embryology and Larval Development
BIOS 236 (Spr)
- Life history variation in the evolution of developmental mechanisms
BIOHOPK 350H (Sum)
BIO 136, BIO 236, GEOLSCI 136, GEOLSCI 236 (Win)
- The Developmental Basis of Animal Body Plan Evolution
BIO 176, BIO 276 (Win)
- Developmental Biology in the Ocean: Comparative Embryology and Larval Development
Graduate and Fellowship Programs
Biology (School of Humanities and Sciences) (Phd Program)
Untangling posterior growth and segmentation by analyzing mechanisms of axis elongation in hemichordates.
Proceedings of the National Academy of Sciences of the United States of America
The trunk is a key feature of the bilaterian body plan. Despite spectacular morphological diversity in bilaterian trunk anatomies, most insights into trunk development are from segmented taxa, namely arthropods and chordates. Mechanisms of posterior axis elongation (PAE) and segmentation are tightly coupled in arthropods and vertebrates, making it challenging to differentiate between the underlying developmental mechanisms specific to each process. Investigating trunk elongation in unsegmented animals facilitates examination of mechanisms specific to PAE and provides a different perspective for testing hypotheses of bilaterian trunk evolution. Here we investigate the developmental roles of canonical Wnt and Notch signaling in the hemichordate Saccoglossus kowalevskii and reveal that both pathways play key roles in PAE immediately following the completion of gastrulation. Furthermore, our functional analysis of the role of Brachyury is supportive of a Wnt-Brachyury feedback loop during PAE in S. kowalevskii, establishing this key regulatory interaction as an ancestral feature of deuterostomes. Together, our results provide valuable data for testing hypotheses of bilaterian trunk evolution.
View details for PubMedID 30967509
I-SceI Meganuclease-mediated transgenesis in the acorn worm, Saccoglossus kowalevskii.
Hemichordates are a phylum of marine invertebrate deuterostomes that are closely related to chordates, and represent one of the most promising models to provide insights into early deuterostome evolution. The genome of the hemichordate, Saccoglossus kowalevskii, reveals an extensive set of non-coding elements conserved across all three deuterostome phyla. Functional characterization and cross-phyla comparisons of these putative regulatory elements will enable a better understanding of enhancer evolution, and subsequently how changes in gene regulation give rise to morphological innovation. Here, we describe an efficient method of transgenesis for the characterization of non-coding elements in S. kowalevskii. We first test the capacity of an I-SceI transgenesis system to drive ubiquitous or regionalized gene expression, and to label specific cell types. Finally, we identified a minimal promoter that can be used to test the capacity of putative enhancers in S. kowalevskii. This work demonstrates that this I-SceI transgenesis technique, when coupled with an understanding of chromatin accessibility, can be a powerful tool for studying how evolutionary changes in gene regulatory mechanisms contributed to the diversification of body plans in deuterostomes.
View details for PubMedID 30412702
Anteroposterior axis patterning by early canonical Wnt signaling during hemichordate development
2018; 16 (1): e2003698
The Wnt family of secreted proteins has been proposed to play a conserved role in early specification of the bilaterian anteroposterior (A/P) axis. This hypothesis is based predominantly on data from vertebrate embryogenesis as well as planarian regeneration and homeostasis, indicating that canonical Wnt (cWnt) signaling endows cells with positional information along the A/P axis. Outside of these phyla, there is strong support for a conserved role of cWnt signaling in the repression of anterior fates, but little comparative support for a conserved role in promotion of posterior fates. We further test the hypothesis by investigating the role of cWnt signaling during early patterning along the A/P axis of the hemichordate Saccoglossus kowalevskii. We have cloned and investigated the expression of the complete Wnt ligand and Frizzled receptor complement of S. kowalevskii during early development along with many secreted Wnt modifiers. Eleven of the 13 Wnt ligands are ectodermally expressed in overlapping domains, predominantly in the posterior, and Wnt antagonists are localized predominantly to the anterior ectoderm in a pattern reminiscent of their distribution in vertebrate embryos. Overexpression and knockdown experiments, in combination with embryological manipulations, establish the importance of cWnt signaling for repression of anterior fates and activation of mid-axial ectodermal fates during the early development of S. kowalevskii. However, surprisingly, terminal posterior fates, defined by posterior Hox genes, are unresponsive to manipulation of cWnt levels during the early establishment of the A/P axis at late blastula and early gastrula. We establish experimental support for a conserved role of Wnt signaling in the early specification of the A/P axis during deuterostome body plan diversification, and further build support for an ancestral role of this pathway in early evolution of the bilaterian A/P axis. We find strong support for a role of cWnt in suppression of anterior fates and promotion of mid-axial fates, but we find no evidence that cWnt signaling plays a role in the early specification of the most posterior axial fates in S. kowalevskii. This posterior autonomy may be a conserved feature of early deuterostome axis specification.
View details for PubMedID 29337984
The Adult Body Plan of Indirect Developing Hemichordates Develops by Adding a Hox-Patterned Trunk to an Anterior Larval Territory
2017; 27 (1): 87-95
Many animals are indirect developers with distinct larval and adult body plans . The molecular basis of differences between larval and adult forms is often poorly understood, adding a level of uncertainty to comparative developmental studies that use data from both indirect and direct developers. Here we compare the larval and adult body plans of an indirect developing hemichordate, Schizocardium californicum . We describe the expression of 27 transcription factors with conserved roles in deuterostome ectodermal anteroposterior (AP) patterning in developing embryos, tornaria larvae, and post-metamorphic juveniles and show that the tornaria larva of S. californicum is transcriptionally similar to a truncated version of the adult. The larval ectoderm has an anterior molecular signature, while most of the trunk, defined by the expression of hox1-7, is absent. Posterior ectodermal activation of Hox is initiated in the late larva prior to metamorphosis, in preparation for the transition to the adult form, in which the AP axis converges on a molecular architecture similar to that of the direct developing hemichordate Saccoglossus kowalevskii. These results identify a molecular correlate of a major difference in body plan between hemichordate larval and adult forms and confirm the hypothesis that deuterostome larvae are "swimming heads" . This will allow future comparative studies with hemichordates to take into account molecular differences caused by early life history evolution within the phylum. Additionally, comparisons with other phyla suggest that a delay in trunk development is a feature of indirect development shared across distantly related phyla.
View details for DOI 10.1016/j.cub.2016.10.047
View details for Web of Science ID 000391902500026
View details for PubMedID 27939313
Cis-regulatory architecture of a brain signaling center predates the origin of chordates
2016; 48 (5): 575-?
Genomic approaches have predicted hundreds of thousands of tissue-specific cis-regulatory sequences, but the determinants critical to their function and evolutionary history are mostly unknown. Here we systematically decode a set of brain enhancers active in the zona limitans intrathalamica (zli), a signaling center essential for vertebrate forebrain development via the secreted morphogen Sonic hedgehog (Shh). We apply a de novo motif analysis tool to identify six position-independent sequence motifs together with their cognate transcription factors that are essential for zli enhancer activity and Shh expression in the mouse embryo. Using knowledge of this regulatory lexicon, we discover new Shh zli enhancers in mice and a functionally equivalent element in hemichordates, indicating an ancient origin of the Shh zli regulatory network that predates the chordate phylum. These findings support a strategy for delineating functionally conserved enhancers in the absence of overt sequence homologies and over extensive evolutionary distances.
View details for DOI 10.1038/ng.3542
View details for PubMedID 27064252
The deuterostome context of chordate origins
2015; 520 (7548): 456-465
Our understanding of vertebrate origins is powerfully informed by comparative morphology, embryology and genomics of chordates, hemichordates and echinoderms, which together make up the deuterostome clade. Striking body-plan differences among these phyla have historically hindered the identification of ancestral morphological features, but recent progress in molecular genetics and embryology has revealed deep similarities in body-axis formation and organization across deuterostomes, at stages before morphological differences develop. These developmental genetic features, along with robust support of pharyngeal gill slits as a shared deuterostome character, provide the foundation for the emergence of chordates.
View details for DOI 10.1038/nature14434
View details for Web of Science ID 000353334500029
View details for PubMedID 25903627
Ancient deuterostome origins of vertebrate brain signalling centres
2012; 483 (7389): 289-U79
Neuroectodermal signalling centres induce and pattern many novel vertebrate brain structures but are absent, or divergent, in invertebrate chordates. This has led to the idea that signalling-centre genetic programs were first assembled in stem vertebrates and potentially drove morphological innovations of the brain. However, this scenario presumes that extant cephalochordates accurately represent ancestral chordate characters, which has not been tested using close chordate outgroups. Here we report that genetic programs homologous to three vertebrate signalling centres-the anterior neural ridge, zona limitans intrathalamica and isthmic organizer-are present in the hemichordate Saccoglossus kowalevskii. Fgf8/17/18 (a single gene homologous to vertebrate Fgf8, Fgf17 and Fgf18), sfrp1/5, hh and wnt1 are expressed in vertebrate-like arrangements in hemichordate ectoderm, and homologous genetic mechanisms regulate ectodermal patterning in both animals. We propose that these genetic programs were components of an unexpectedly complex, ancient genetic regulatory scaffold for deuterostome body patterning that degenerated in amphioxus and ascidians, but was retained to pattern divergent structures in hemichordates and vertebrates.
View details for DOI 10.1038/nature10838
View details for Web of Science ID 000301481800040
View details for PubMedID 22422262
The Cadherin-Catenin Complex is Necessary for Cell Adhesion and Embryogenesis in Nematostella vectensis.
The cadherin-catenin complex is a conserved, calcium-dependent cell-cell adhesion module that is necessary for normal development and the maintenance of tissue integrity in bilaterian animals. Despite longstanding evidence of a deep ancestry of calcium-dependent cell adhesion in animals, the requirement of the cadherin-catenin complex to coordinate cell-cell adhesion has not been tested directly in a non-bilaterian organism. Here, we provide the first analysis of classical cadherins and catenins in the Starlet Sea Anemone, Nematostella vectensis. Gene expression, protein localization, siRNA-mediated knockdown of alpha-catenin, and calcium-dependent cell aggregation assays provide evidence that a bonafide cadherin-catenin complex is present in the early embryo, and that alpha-catenin is required for normal embryonic development and the formation of cell-cell adhesions between cells dissociated from whole embryos. Together these results support the hypothesis that the cadherin-catenin complex was likely a complete and functional cell-cell adhesion module in the last common cnidarian-bilaterian ancestor.
View details for PubMedID 30629955
- The development and metamorphosis of the indirect developing acorn worm Schizocardium californicum (Enteropneusta: Spengelidae) FRONTIERS IN ZOOLOGY 2018; 15
Characterization of the Cadherin-Catenin Complex of the Sea Anemone Nematostella vectensis and Implications for the Evolution of Metazoan Cell-Cell Adhesion
MOLECULAR BIOLOGY AND EVOLUTION
2016; 33 (8): 2016-2029
The cadherin-catenin complex (CCC) mediates cell-cell adhesion in bilaterian animals by linking extracellular cadherin-based adhesions to the actin cytoskeleton. However, it is unknown whether the basic organization of the complex is conserved across all metazoans. We tested whether protein interactions and actin-binding properties of the CCC are conserved in a nonbilaterian animal, the sea anemone Nematostella vectensis We demonstrated that N. vectensis has a complete repertoire of cadherin-catenin proteins, including two classical cadherins, one α-catenin, and one β-catenin. Using size-exclusion chromatography and multi-angle light scattering, we showed that α-catenin and β-catenin formed a heterodimer that bound N. vectensis Cadherin-1 and -2. Nematostella vectensis α-catenin bound F-actin with equivalent affinity as either a monomer or an α/β-catenin heterodimer, and its affinity for F-actin was, in part, regulated by a novel insert between the N- and C-terminal domains. Nematostella vectensis α-catenin inhibited Arp2/3 complex-mediated nucleation of actin filaments, a regulatory property previously thought to be unique to mammalian αE-catenin. Thus, despite significant differences in sequence, the key interactions of the CCC are conserved between bilaterians and cnidarians, indicating that the core function of the CCC as a link between cell adhesions and the actin cytoskeleton is ancestral in the eumetazoans.
View details for DOI 10.1093/molbev/msw084
View details for Web of Science ID 000380105900011
View details for PubMedID 27189570
View details for PubMedCentralID PMC4948710
- Embracing the comparative approach: how robust phylogenies and broader developmental sampling impacts the understanding of nervous system evolution PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES 2015; 370 (1684)
On a Possible Evolutionary Link of the Stomochord of Hemichordates to Pharyngeal Organs of Chordates
2014; 52 (12): 925-934
As a group closely related to chordates, hemichordate acorn worms are in a key phylogenic position for addressing hypotheses of chordate origins. The stomochord of acorn worms is an anterior outgrowth of the pharynx endoderm into the proboscis. In 1886 Bateson proposed homology of this organ to the chordate notochord, crowning this animal group "hemichordates." Although this proposal has been debated for over a century, the question still remains unresolved. Here we review recent progress related to this question. First, the developmental mode of the stomochord completely differs from that of the notochord. Second, comparison of expression profiles of genes including Brachyury, a key regulator of notochord formation in chordates, does not support the stomochord/notochord homology. Third, FoxE that is expressed in the stomochord-forming region in acorn worm juveniles is expressed in the club-shaped gland and in the endostyle of amphioxus, in the endostyle of ascidians, and in the thyroid gland of vertebrates. Based on these findings, together with the anterior endodermal location of the stomochord, we propose that the stomochord has evolutionary relatedness to chordate organs deriving from the anterior pharynx rather than to the notochord.
View details for DOI 10.1002/dvg.22831
View details for Web of Science ID 000346702100001
View details for PubMedID 25303744
Animal evolution: stiff or squishy notochord origins?
2014; 24 (23): R1131-3
The notochord is considered an evolutionary novelty and one of the defining characters of chordates. A new study of an annelid challenges this view and proposes an earlier evolutionary origin in the most recent common ancestor of chordates and annelids.
View details for DOI 10.1016/j.cub.2014.10.059
View details for PubMedID 25465334
Phylogenomic analysis of echinoderm class relationships supports Asterozoa
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
2014; 281 (1786)
While some aspects of the phylogeny of the five living echinoderm classes are clear, the position of the ophiuroids (brittlestars) relative to asteroids (starfish), echinoids (sea urchins) and holothurians (sea cucumbers) is controversial. Ophiuroids have a pluteus-type larva in common with echinoids giving some support to an ophiuroid/echinoid/holothurian clade named Cryptosyringida. Most molecular phylogenetic studies, however, support an ophiuroid/asteroid clade (Asterozoa) implying either convergent evolution of the pluteus or reversals to an auricularia-type larva in asteroids and holothurians. A recent study of 10 genes from four of the five echinoderm classes used 'phylogenetic signal dissection' to separate alignment positions into subsets of (i) suboptimal, heterogeneously evolving sites (invariant plus rapidly changing) and (ii) the remaining optimal, homogeneously evolving sites. Along with most previous molecular phylogenetic studies, their set of heterogeneous sites, expected to be more prone to systematic error, support Asterozoa. The homogeneous sites, in contrast, support an ophiuroid/echinoid grouping, consistent with the cryptosyringid clade, leading them to posit homology of the ophiopluteus and echinopluteus. Our new dataset comprises 219 genes from all echinoderm classes; analyses using probabilistic Bayesian phylogenetic methods strongly support Asterozoa. The most reliable, slowly evolving quartile of genes also gives highest support for Asterozoa; this support diminishes in second and third quartiles and the fastest changing quartile places the ophiuroids close to the root. Using phylogenetic signal dissection, we find heterogenous sites support an unlikely grouping of Ophiuroidea + Holothuria while homogeneous sites again strongly support Asterozoa. Our large and taxonomically complete dataset finds no support for the cryptosyringid hypothesis; in showing strong support for the Asterozoa, our preferred topology leaves the question of homology of pluteus larvae open.
View details for DOI 10.1098/rspb.2014.0479
View details for Web of Science ID 000336784500021
View details for PubMedCentralID PMC4046411
- The Fox/Forkhead transcription factor family of the hemichordate Saccoglossus kowalevskii EVODEVO 2014; 5
The Fox/Forkhead transcription factor family of the hemichordate Saccoglossus kowalevskii.
2014; 5: 17-?
The Fox gene family is a large family of transcription factors that arose early in organismal evolution dating back to at least the common ancestor of metazoans and fungi. They are key components of many gene regulatory networks essential for embryonic development. Although much is known about the role of Fox genes during vertebrate development, comprehensive comparative studies outside vertebrates are sparse. We have characterized the Fox transcription factor gene family from the genome of the enteropneust hemichordate Saccoglossus kowalevskii, including phylogenetic analysis, genomic organization, and expression analysis during early development. Hemichordates are a sister group to echinoderms, closely related to chordates and are a key group for tracing the evolution of gene regulatory mechanisms likely to have been important in the diversification of the deuterostome phyla.Of the 22 Fox gene families that were likely present in the last common ancestor of all deuterostomes, S. kowalevskii has a single ortholog of each group except FoxH, which we were unable to detect, and FoxQ2, which has three paralogs. A phylogenetic analysis of the FoxQ2 family identified an ancestral duplication in the FoxQ2 lineage at the base of the bilaterians. The expression analyses of all 23 Fox genes of S. kowalevskii provide insights into the evolution of components of the regulatory networks for the development of pharyngeal gill slits (foxC, foxL1, and foxI), mesoderm patterning (foxD, foxF, foxG), hindgut development (foxD, foxI), cilia formation (foxJ1), and patterning of the embryonic apical territory (foxQ2).Comparisons of our results with data from echinoderms, chordates, and other bilaterians help to develop hypotheses about the developmental roles of Fox genes that likely characterized ancestral deuterostomes and bilaterians, and more recent clade-specific innovations.
View details for DOI 10.1186/2041-9139-5-17
View details for PubMedID 24987514
View details for PubMedCentralID PMC4077281
FGF signaling induces mesoderm in the hemichordate Saccoglossus kowalevskii
2013; 140 (5): 1024-1033
FGFs act in vertebrate mesoderm induction and also play key roles in early mesoderm formation in ascidians and amphioxus. However, in sea urchins initial characterizations of FGF function do not support a role in early mesoderm induction, making the ancestral roles of FGF signaling and mechanisms of mesoderm specification in deuterostomes unclear. In order to better characterize the evolution of mesoderm formation, we have examined the role of FGF signaling during mesoderm development in Saccoglossus kowalevskii, an experimentally tractable representative of hemichordates. We report the expression of an FGF ligand, fgf8/17/18, in ectoderm overlying sites of mesoderm specification within the archenteron endomesoderm. Embryological experiments demonstrate that mesoderm induction in the archenteron requires contact with ectoderm, and loss-of-function experiments indicate that both FGF ligand and receptor are necessary for mesoderm specification. fgf8/17/18 gain-of-function experiments establish that FGF8/17/18 is sufficient to induce mesoderm in adjacent endomesoderm. These experiments suggest that FGF signaling is necessary from the earliest stages of mesoderm specification and is required for all mesoderm development. Furthermore, they suggest that the archenteron is competent to form mesoderm or endoderm, and that FGF signaling from the ectoderm defines the location and amount of mesoderm. When considered in a comparative context, these data support a phylogenetically broad requirement for FGF8/17/18 signaling in mesoderm specification and suggest that FGF signaling played an ancestral role in deuterostome mesoderm formation.
View details for DOI 10.1242/dev.083790
View details for Web of Science ID 000314879800011
View details for PubMedID 23344709
The evolutionary origin of epithelial cell-cell adhesion mechanisms.
Current topics in membranes
2013; 72: 267-311
A simple epithelium forms a barrier between the outside and the inside of an organism, and is the first organized multicellular tissue found in evolution. We examine the relationship between the evolution of epithelia and specialized cell-cell adhesion proteins comprising the classical cadherin/β-catenin/α-catenin complex (CCC). A review of the divergent functional properties of the CCC in metazoans and non-metazoans, and an updated phylogenetic coverage of the CCC using recent genomic data reveal: (1) The core CCC likely originated before the last common ancestor of unikonts and their closest bikont sister taxa. (2) Formation of the CCC may have constrained sequence evolution of the classical cadherin cytoplasmic domain and β-catenin in metazoa. (3) The α-catenin-binding domain in β-catenin appears to be the favored mutation site for disrupting β-catenin function in the CCC. (4) The ancestral function of the α/β-catenin heterodimer appears to be an actin-binding module. In some metazoan groups, more complex functions of α-catenin were gained by sequence divergence in the non-actin-binding (N-, M-) domains. (5) Allosteric regulation of α-catenin may have evolved for more complex regulation of the actin cytoskeleton.
View details for DOI 10.1016/B978-0-12-417027-8.00008-8
View details for PubMedID 24210433
View details for PubMedCentralID PMC4118598
Identical Genomic Organization of Two Hemichordate Hox Clusters
2012; 22 (21): 2053-2058
Genomic comparisons of chordates, hemichordates, and echinoderms can inform hypotheses for the evolution of these strikingly different phyla from the last common deuterostome ancestor. Because hox genes play pivotal developmental roles in bilaterian animals, we analyzed the Hox complexes of two hemichordate genomes. We find that Saccoglossus kowalevskii and Ptychodera flava both possess 12-gene clusters, with mir10 between hox4 and hox5, in 550 kb and 452 kb intervals, respectively. Genes hox1-hox9/10 of the clusters are in the same genomic order and transcriptional orientation as their orthologs in chordates, with hox1 at the 3' end of the cluster. At the 5' end, each cluster contains three posterior genes specific to Ambulacraria (the hemichordate-echinoderm clade), two forming an inverted terminal pair. In contrast, the echinoderm Strongylocentrotus purpuratus contains a 588 kb cluster of 11 orthologs of the hemichordate genes, ordered differently, plausibly reflecting rearrangements of an ancestral hemichordate-like ambulacrarian cluster. Hox clusters of vertebrates and the basal chordate amphioxus have similar organization to the hemichordate cluster, but with different posterior genes. These results provide genomic evidence for a well-ordered complex in the deuterostome ancestor for the hox1-hox9/10 region, with the number and kind of posterior genes still to be elucidated.
View details for DOI 10.1016/j.cub.2012.08.052
View details for Web of Science ID 000311060200028
View details for PubMedID 23063438
- Evolutionary crossroads in developmental biology: hemichordates DEVELOPMENT 2012; 139 (14): 2463-2475
Animal Evolution: A Soap Opera of Unremarkable Worms
2011; 21 (4): R151-R153
Recent phylogenies have suggested that acoelomorph flatworms might provide insights into the nature of the ancestor of bilaterian animals. However, according to new data acoelomorphs might instead be degenerate deuterostomes closely related to Xenoturbella, muddying the waters of early animal evolution.
View details for Web of Science ID 000287767600008
View details for PubMedID 21334293
Structural shifts of aldehyde dehydrogenase enzymes were instrumental for the early evolution of retinoid-dependent axial patterning in metazoans
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
2011; 108 (1): 226-231
Aldehyde dehydrogenases (ALDHs) catabolize toxic aldehydes and process the vitamin A-derived retinaldehyde into retinoic acid (RA), a small diffusible molecule and a pivotal chordate morphogen. In this study, we combine phylogenetic, structural, genomic, and developmental gene expression analyses to examine the evolutionary origins of ALDH substrate preference. Structural modeling reveals that processing of small aldehydes, such as acetaldehyde, by ALDH2, versus large aldehydes, including retinaldehyde, by ALDH1A is associated with small versus large substrate entry channels (SECs), respectively. Moreover, we show that metazoan ALDH1s and ALDH2s are members of a single ALDH1/2 clade and that during evolution, eukaryote ALDH1/2s often switched between large and small SECs after gene duplication, transforming constricted channels into wide opened ones and vice versa. Ancestral sequence reconstructions suggest that during the evolutionary emergence of RA signaling, the ancestral, narrow-channeled metazoan ALDH1/2 gave rise to large ALDH1 channels capable of accommodating bulky aldehydes, such as retinaldehyde, supporting the view that retinoid-dependent signaling arose from ancestral cellular detoxification mechanisms. Our analyses also indicate that, on a more restricted evolutionary scale, ALDH1 duplicates from invertebrate chordates (amphioxus and ascidian tunicates) underwent switches to smaller and narrower SECs. When combined with alterations in gene expression, these switches led to neofunctionalization from ALDH1-like roles in embryonic patterning to systemic, ALDH2-like roles, suggesting functional shifts from signaling to detoxification.
View details for DOI 10.1073/pnas.1011223108
View details for Web of Science ID 000285915000044
View details for PubMedID 21169504