Biology subjects

Baxevanis, A. D.

Publications and source records attributed to Baxevanis, A. D..

13 recordsLinked to original sources

bioRxiv2026

An Ancient, Structurally Conserved Allorecognition Gene Complex Predates the Divergence of Major Cnidarian Lineages

The allorecognition system of the hydroid Hydractinia symbiolongicarpus plays an essential role in mediating self vs. non-self recognition among cnidarian colonies, analogous to the role of the major histocompatibility complex (MHC) in bilaterian immune systems. Both complexes have contiguous stretches of similar, highly duplicated genes, suggesting a homologous relationship. Protein structural prediction methods such as AlphaFold2 also indicate structural similarity between the proteins encoded within the Hydractinia ARC and the MHC. We have determined the structure of the ARC in the related hydrozoan Podocoryna americana to determine the degree of conservation of the cnidarian allorecognition complex. Protein structural prediction methods have revealed a number of candidate allorecognition proteins that form a long contiguous complex. Phylogenies suggest homology between cnidarian allorecognition genes, as well as syntenic conservation of this gene complex across hydrozoans. Ongoing comparative genomic analyses across bilaterian species aim to clarify the relationship between the ARC and the MHC, thereby informing our understanding of the evolutionary origins of bilaterian adaptive immunity.

evolutionary biology↗

bioRxiv2026

A chromosome-level reference genome for the colonial marine hydrozoan Podocoryna americana

Cnidarians are important models for the studying the evolution of animal development, regeneration, cell type differentiation, and allorecognition. The marine hydrozoan Podocoryna americana is related to the well-established model species Hydractinia symbiolongicarpus. Although both species possess a sessile polyp stage, P. americana differs in that it also has a free-swimming medusa (jellyfish) stage in its life cycle. We used a combination of PacBio CLR long-read and Illumina Hi-C short-read genome sequencing to produce a chromosome-level genome assembly for P. americana. The final assembly is 327 Mbp in total length with 17 chromosome-scale scaffolds representing 98% of the assembly. Comprehensive functional annotation with BRAKER3 generated a total of 19,085 predicted protein-coding genes in this assembly, covering 91.2% of the metazoan BUCSO gene set. Comparison of the P. americana genome to other chromosome-level cnidarian genome assemblies revealed a high degree of macrosynteny conservation, and ortholog identification and gene family evolution analysis identified 522 expanded and 1,026 contracted gene families in P. americana. This high-quality, chromosome-level genome assembly of P. americana will be an invaluable resource for researchers studying the evolution of development, regeneration, and allorecognition in cnidarians and other metazoans.

genomics↗

bioRxiv2025

A chromosome-level assembly and functional genomic resources for the model annelid Capitella teleta

BackgroundThe polychaete Capitella teleta is a commonly used annelid for studies in evolutionary developmental biology, comparative genomics, conservation, and ecotoxicology. Over a decade ago, it was the first polychaete to have its genome sequenced and assembled, contributing to pioneering studies that transformed our understanding of animal genomes and their evolution. However, this early resource is now outdated compared to current genome sequencing standards, limiting the use of modern functional genomic tools that could further our understanding of numerous biological processes. ResultsWe combine long-read and short-read sequencing with Hi-C chromatin conformation capture data to assemble the chromosome-level nuclear and mitochondrial genomes of the laboratory strain of C. teleta. This reference assembly more accurately reflects the expected genome size for this polychaete ([~]243.6 Mb) and contains a highly complete, evolutionarily conserved gene repertoire. Notably, the nuclear and mitochondrial genomes are heavily rearranged, indicating a decoupling between gene family repertoire and chromosomal evolution. The analyses of multi-omic datasets available for C. teleta, including developmental time courses of bulk and single-cell RNA-seq, ATAC-seq, and EM-seq, using the new reference assembly, resulted in a significant quality improvement, allowing us to identify new cell-type-specific gene markers and gain additional insights of biological relevance. Finally, we generated a publicly available genome browser that ensures all these resources are easily findable, accessible, interoperable, and reusable. ConclusionsOur study provides state-of-the-art genomic resources for the polychaete model C. teleta, addressing a pressing community need that will open new research opportunities in animal and genome evolution.

genomics↗

bioRxiv2025

An updated and spatially validated somatic single-cell atlas of Hydractinia symbiolongicarpus

Single-cell RNA sequencing (scRNA-seq) has revolutionized transcriptomic research, enabling the creation of detailed tissue, organ, and species-level atlases for model organisms. In Hydractinia, a cnidarian model for stem cell and regeneration studies, recent atlases have revealed key insights into cell types and developmental processes. However, these atlases remain limited in cell numbers and transcriptomic depth and cell type assignments were largely made in silico. Here, we present an updated Hydractinia single-cell atlas by integrating new datasets from fixed cells with previously published live-cell data. This expanded atlas captures over 47,000 cells from feeding polyps and stolon tissue, recovering and refining major somatic cell lineages including cnidocytes, neurons, gland cells, epithelial cells, and stem cells (i-cells), as well as identifying a novel population of putative immune cells. We investigated the spatial expression patterns of selected marker genes and validated all major cell types and several cell states. Our analyses uncovered a previously undescribed neural subtype, two spatially distinct gland cell populations, a stolon-specific cell type, and a putative immune cell cluster. Additionally, we recovered and explored a complete Hydractinia cnidocyte trajectory with two distinct endpoints, supported by spatial marker gene expression that reflects the developmental progression of cnidoblasts as they mature and migrate towards the tentacles. Subclustering of somatic i-cells revealed putative progenitor states and a potential population of true stem cells. Together, this atlas significantly advances our understanding of Hydractinia cellular diversity and dynamics, allowing us to generate new hypotheses and provide a valuable resource for the cnidarian research community and beyond.

evolutionary biology↗

bioRxiv2024

Rapid speciation in the holopelagic ctenophore Mnemiopsis following glacial recession

BackgroundUnderstanding how populations diverge is one of the most compelling questions in evolutionary biology but our grasp on the genomic mechanisms underpinning divergence is limited to a handful of species. Indeed, we know even less about divergence in the pelagic zone, where barriers to gene flow are seemingly absent. The holopelagic ctenophore Mnemiopsis leidyi is the most widely used ctenophore in experimental biology and has become an important model system in studies ranging from developmental biology to neurobiology. In addition, its relatively small and tractable genome provides a powerful foundation for genomic and evolutionary analyses. However, we still lack a clear understanding of species boundaries, population structure, and the evolutionary forces shaping divergence within Mnemiopsis, limiting both evolutionary and ecological interpretations. To expand our general understanding of divergence across novel environments as well as resolve a long-standing taxonomic debate, we generated the most comprehensive genomic study to date of the holopelagic ctenophore Mnemiopsis across a large expanse of its native range. ResultsBy leveraging multiple analytical approaches and generating two near-chromosome level genomes, we identify two distinct species of Mnemiopsis with high levels of genome-wide divergence along the US Atlantic coast, which correspond to M. leidyi and M. gardeni. Our demographic analyses suggest that M. leidyi and M. gardeni began to diverge during the mid-to-late Pleistocene climate transitions and were later shaped by post-glacial oceanographic changes. We highlight substantial genomic rearrangements and copy number variation between species as well as uncover key genes under selection that are likely important for environmental adaptation. ConclusionsTogether, these findings provide compelling evidence that the ctenophore currently recognized as M. leidyi represents more than one species. Recognizing cryptic species boundaries is critical for future study designs, environmental monitoring, and developing targeted management strategies. Altogether, we connect microevolutionary processes with macroevolutionary patterns and provide new insights into how ocean dynamics drive speciation and adaptation in pelagic ecosystems.

evolutionary biology↗

bioRxiv2023

The genome of the colonial hydroid Hydractinia reveals their stem cells use a toolkit of genes shared with all animals

Hydractinia is a colonial marine hydroid that exhibits remarkable biological properties, including the capacity to regenerate its entire body throughout its lifetime, a process made possible by its adult migratory stem cells, known as i-cells. Here, we provide an in-depth characterization of the genomic structure and gene content of two Hydractinia species, H. symbiolongicarpus and H. echinata, placing them in a comparative evolutionary framework with other cnidarian genomes. We also generated and annotated a single-cell transcriptomic atlas for adult male H. symbiolongicarpus and identified cell type markers for all major cell types, including key i-cell markers. Orthology analyses based on the markers revealed that Hydractinias i-cells are highly enriched in genes that are widely shared amongst animals, a striking finding given that Hydractinia has a higher proportion of phylum-specific genes than any of the other 41 animals in our orthology analysis. These results indicate that Hydractinias stem cells and early progenitor cells may use a toolkit shared with all animals, making it a promising model organism for future exploration of stem cell biology and regenerative medicine. The genomic and transcriptomic resources for Hydractinia presented here will enable further studies of their regenerative capacity, colonial morphology, and ability to distinguish self from non-self.

genomics↗

bioRxiv2022

Senescence-induced cellular reprogramming drives cnidarian whole-body regeneration

Cell fate stability is essential to maintaining law and order in complex animals. However, high stability comes at the cost of reduced plasticity and, by extension, poor regenerative ability. This evolutionary trade-off has resulted in most modern animals being rather simple and regenerative or complex and non-regenerative. The mechanisms mediating cellular plasticity and allowing for regeneration remain unknown. We show that signals emitted by senescent cells can destabilize the differentiated state of neighboring somatic cells, reprogramming them into stem cells that are capable of driving whole-body regeneration in the cnidarian Hydractinia symbiolongicarpus. Pharmacological or genetic inhibition of senescence prevented reprogramming and regeneration. Conversely, induction of transient ectopic senescence in a regenerative context resulted in supernumerary stem cells and faster regeneration. We propose that senescence signaling is an ancient mechanism mediating cellular plasticity. Understanding the senescence environment that promotes cellular reprogramming could provide a new avenue to enhance regeneration.

developmental biology↗

bioRxiv2022

New Hydra Genomes Reveal Conserved Principles of Hydrozoan Transcriptional Regulation

The epithelial and interstitial stem cells of the freshwater polyp Hydra are the best characterized stem cell systems in any cnidarian, providing valuable insight into cell type evolution and the origin of stemness in animals. However, little is known about the transcriptional regulatory mechanisms that determine how these stem cells are maintained and how they give rise to their diverse differentiated progeny. To address such questions, a thorough understanding of transcriptional regulation in Hydra is needed. To this end, we generated extensive new resources for characterizing transcriptional regulation in Hydra, including new genome assemblies for Hydra oligactis and the AEP strain of Hydra vulgaris, an updated whole-animal single-cell RNA-seq atlas, and genome-wide maps of chromatin interactions, chromatin accessibility, sequence conservation, and histone modifications. These data revealed the existence of large chromatin interaction domains in the Hydra genome that likely influence transcriptional regulation in a manner distinct from topologically associating domains in bilaterians. We also uncovered the transcriptomic profiles of two previously molecularly uncharacterized cell types, isorhiza-containing nematocytes and somatic gonad ectoderm. We identified novel candidate regulators of cell-type-specific transcription, several of which have likely been conserved at least since the divergence of Hydra and the jellyfish Clytia hemisphaerica over 200 million years ago. The resources generated in this study, which collectively represent the most comprehensive characterization of transcriptional regulation in a cnidarian to date, are accessible through a newly created genome portal, available at research.nhgri.nih.gov/HydraAEP/.

developmental biology↗

bioRxiv2022

XY sex determination in a cnidarian

Sex determination occurs across animal species, but most of our knowledge about the mechanisms of sex determination comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used this map to determine that this species has an XX/XY sex determination system. We delineate the pseudoautosomal and non-recombining regions of the Y chromosome and show that the latter encodes a number of genes with male gonad-specific expression. These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination. Significance StatementWhat determines whether an animal is male or female? The answer depends on the species. Some rely on signals from their environment, while others take cues from their genome. Most of what we understand about sex determination comes from traditional model organisms (such as mice, flies, and worms) or groups of well-studied vertebrates and insects. Studying sex determination in other animals, especially those from phyla that diverged early in animal evolution, would allow us to better understand how sex has evolved across the animal kingdom and could reveal pathways present in the eumetazoan ancestor >600 million years ago. In this study, we show that the cnidarian Hydractinia symbiolongicarpus has XY sex determination, establishing this species as a model system for sex determination in an understudied group of animals.

genetics↗

bioRxiv2022

The Hydractinia Allorecognition Complex encodes a novel family of immunoglobulin superfamily proteins

Most colonial marine invertebrates are capable of allorecognition, the ability to distinguish between themselves and conspecifics. One long-standing question is whether invertebrate allorecognition genes are homologous to vertebrate histocompatibility genes. In the cnidarian Hydractinia symbiolongicarpus, allorecognition is controlled by at least two genes, Allorecognition 1 (Alr1) and Allorecognition 2 (Alr2), which encode highly polymorphic cell surface proteins that serve as markers of self. Here, we show that Alr1 and Alr2 are part of a family of 41 Alr genes, all of which reside a single genomic interval called the Allorecognition Complex (ARC). Using sensitive homology searches and highly accurate structural predictions, we demonstrate that the Alr proteins are members of the immunoglobulin superfamily (IgSF) with V-set and I-set Ig domains unlike any previously identified in animals. Specifically, their primary amino acid sequences lack many of the motifs considered diagnostic for V-set and I-set domains, yet they adopt secondary and tertiary structures nearly identical to canonical Ig domains. Thus, the V-set domain, which played a central role in the evolution of vertebrate adaptive immunity, was present in the last common ancestor of cnidarians and bilaterians. Unexpectedly, several Alr proteins also have immunoreceptor tyrosine-based activation motifs (ITAMs) and immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic tails, suggesting they could participate in pathways homologous to those that regulate immunity in humans and flies. This work expands our definition of the IgSF with the addition of a family of unusual members, several of which play a role in invertebrate histocompatibility. Significance StatementThe immunoglobulin superfamily (IgSF) is one of the largest and most functionally versatile domain families in animal genomes. Although their amino acid sequences can vary considerably, IgSF domains have been traditionally defined by conserved residues at several key positions in their fold. Here, we sequenced an invertebrate histocompatibility complex and discovered a family of IgSF genes with amino acid sequences that lack most of these residues yet are predicted to adopt folds virtually identical to canonical V-set and I-set IgSF domains. This work broadens the definition of the IgSF and shows that the V-set domain was present earlier in animal evolution than previously appreciated.

genomics↗

bioRxiv2020

AniProtDB: A Collection of Uniformly Generated Metazoan Proteomes for Comparative Genomics Studies

To address the void in the availability of high-quality proteomic data traversing the animal tree, we have implemented a pipeline for generating de novo assemblies based on publicly available data from the NCBI Sequence Read Archive, yielding a comprehensive collection of proteomes from 100 species spanning 21 animal phyla. We have also created the Animal Proteome Database (AniProtDB), a resource providing open access to this collection of high-quality metazoan proteomes, along with information on predicted proteins and protein domains for each taxonomic classification and the ability to perform sequence similarity searches against all proteomes generated using this pipeline. This solution vastly increases the utility of these data by removing the barrier to access for research groups who do not have the expertise or resources to generate these data themselves and enables the use of data from non-traditional research organisms that have the potential to address key questions in biomedicine. Database URLhttps://research.nhgri.nih.gov/aniprotdb

genomics↗

bioRxiv2019

Profiling the endothelial translatome in vivo using ‘AngioTag’ zebrafish

Vascular endothelial cells in vivo are exquisitely regulated by their local environment, which is disrupted or absent when using methods such as FACS sorting of cells isolated from animals or in vitro cell culture. Here, we profile the gene expression patterns of undisturbed endothelial cells in living animals using a novel "AngioTag" zebrafish transgenic line that permits isolation of actively translating mRNAs from endothelial cells in their native environment. This transgenic line uses the endothelial cell-specific kdrl promoter to drive expression of an epitope tagged Rpl10a 60S ribosomal subunit protein, allowing for Translating Ribosome Affinity Purification (TRAP) of actively translating endothelial cell mRNAs. By performing TRAP-RNAseq on AngioTag animals, we demonstrate strong enrichment of endothelial specific genes and uncover novel endothelial genes and unique endothelial gene expression signatures for different adult organs. Finally, we generated a versatile "UAS:RiboTag" transgenic line to allow a wider array of different zebrafish cell and tissue types to be examined using TRAP-RNAseq methods. These new tools offer an unparalleled resource to study the molecular identity of cells in their normal in vivo context.

developmental biology↗

bioRxiv2018

CRISPR/Cas9-mediated gene knockin in the hydroid Hydractinia symbiolongicarpus

BackgroundHydractinia symbiolongicarpus, a colonial cnidarian, is a tractable model system for many cnidarian-specific and general biological questions. Until recently, tests of gene function in Hydractinia have relied on laborious forward genetic approaches, randomly integrated transgenes, or transient knockdown of mRNAs.\n\nResultsHere, we report the use of CRISPR/Cas9 genome editing to generate targeted genomic insertions in H. symbiolonigcarpus. We used CRISPR/Cas9 to promote homologous recombination of two fluorescent reporters, eGFP and tdTomato, into the Eukaryotic elongation factor 1 alpha (Eef1a) locus. We demonstrate that the transgenes are expressed ubiquitously and are stable over two generations of breeding. We further demonstrate that CRISPR/Cas9 genome editing can be used to mark endogenous proteins with FLAG or StrepII-FLAG affinity tags to enable in vivo and ex vivo protein studies.\n\nConclusionsThis is the first account of CRISPR/Cas9 mediated knockins in Hydractinia and the first example of the germline transmission of a CRISPR/Cas9 inserted transgene in a cnidarian. The ability to precisely insert exogenous DNA into the Hydractinia genome will enable sophisticated genetic studies and further development of functional genomics tools in this understudied cnidarian model.

molecular biology↗