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

Hydractinia is a colonial marine hydroid that shows 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, Hydractinia symbiolongicarpus and Hydractinia 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 Hydractinia's 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 Hydractinia's 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 nonself.

XY sex determination in a cnidarian.

BACKGROUND: Sex determination occurs across animal species, but most of our knowledge about its mechanisms comes from only a handful of bilaterian taxa. This limits our ability to infer the evolutionary history of sex determination within animals. RESULTS: In this study, we generated a linkage map of the genome of the colonial cnidarian Hydractinia symbiolongicarpus and used it to demonstrate that this species has an XX/XY sex determination system. We demonstrate that the X and Y chromosomes have pseudoautosomal and non-recombining regions. We then use the linkage map and a method based on the depth of sequencing coverage to identify genes encoded in the non-recombining region and show that many of them have male gonad-specific expression. In addition, we demonstrate that recombination rates are enhanced in the female genome and that the haploid chromosome number in Hydractinia is n = 15. CONCLUSIONS: These findings establish Hydractinia as a tractable non-bilaterian model system for the study of sex determination and the evolution of sex chromosomes.

The NIH Comparative Genomics Resource: addressing the promises and challenges of comparative genomics on human health.

Comparative genomics is the comparison of genetic information within and across organisms to understand the evolution, structure, and function of genes, proteins, and non-coding regions (Sivashankari and Shanmughavel, Bioinformation 1:376-8, 2007). Advances in sequencing technology and assembly algorithms have resulted in the ability to sequence large genomes and provided a wealth of data that are being used in comparative genomic analyses. Comparative analysis can be leveraged to systematically explore and evaluate the biological relationships and evolution between species, aid in understanding the structure and function of genes, and gain a better understanding of disease and potential drug targets. As our knowledge of genetics expands, comparative genomics can help identify emerging model organisms among a broader span of the tree of life, positively impacting human health. This impact includes, but is not limited to, zoonotic disease research, therapeutics development, microbiome research, xenotransplantation, oncology, and toxicology. Despite advancements in comparative genomics, new challenges have arisen around the quantity, quality assurance, annotation, and interoperability of genomic data and metadata. New tools and approaches are required to meet these challenges and fulfill the needs of researchers. This paper focuses on how the National Institutes of Health (NIH) Comparative Genomics Resource (CGR) can address both the opportunities for comparative genomics to further impact human health and confront an increasingly complex set of challenges facing researchers.

A cnidarian parasite of salmon (Myxozoa: Henneguya) lacks a mitochondrial genome.

Although aerobic respiration is a hallmark of eukaryotes, a few unicellular lineages, growing in hypoxic environments, have secondarily lost this ability. In the absence of oxygen, the mitochondria of these organisms have lost all or parts of their genomes and evolved into mitochondria-related organelles (MROs). There has been debate regarding the presence of MROs in animals. Using deep sequencing approaches, we discovered that a member of the Cnidaria, the myxozoan Henneguya salminicola, has no mitochondrial genome, and thus has lost the ability to perform aerobic cellular respiration. This indicates that these core eukaryotic features are not ubiquitous among animals. Our analyses suggest that H. salminicola lost not only its mitochondrial genome but also nearly all nuclear genes involved in transcription and replication of the mitochondrial genome. In contrast, we identified many genes that encode proteins involved in other mitochondrial pathways and determined that genes involved in aerobic respiration or mitochondrial DNA replication were either absent or present only as pseudogenes. As a control, we used the same sequencing and annotation methods to show that a closely related myxozoan, Myxobolus squamalis, has a mitochondrial genome. The molecular results are supported by fluorescence micrographs, which show the presence of mitochondrial DNA in M. squamalis, but not in H. salminicola. Our discovery confirms that adaptation to an anaerobic environment is not unique to single-celled eukaryotes, but has also evolved in a multicellular, parasitic animal. Hence, H. salminicola provides an opportunity for understanding the evolutionary transition from an aerobic to an exclusive anaerobic metabolism.

Genomic insights into the evolutionary origin of Myxozoa within Cnidaria.

The Myxozoa comprise over 2,000 species of microscopic obligate parasites that use both invertebrate and vertebrate hosts as part of their life cycle. Although the evolutionary origin of myxozoans has been elusive, a close relationship with cnidarians, a group that includes corals, sea anemones, jellyfish, and hydroids, is supported by some phylogenetic studies and the observation that the distinctive myxozoan structure, the polar capsule, is remarkably similar to the stinging structures (nematocysts) in cnidarians. To gain insight into the extreme evolutionary transition from a free-living cnidarian to a microscopic endoparasite, we analyzed genomic and transcriptomic assemblies from two distantly related myxozoan species, Kudoa iwatai and Myxobolus cerebralis, and compared these to the transcriptome and genome of the less reduced cnidarian parasite, Polypodium hydriforme. A phylogenomic analysis, using for the first time to our knowledge, a taxonomic sampling that represents the breadth of myxozoan diversity, including four newly generated myxozoan assemblies, confirms that myxozoans are cnidarians and are a sister taxon to P. hydriforme. Estimations of genome size reveal that myxozoans have one of the smallest reported animal genomes. Gene enrichment analyses show depletion of expressed genes in categories related to development, cell differentiation, and cell-cell communication. In addition, a search for candidate genes indicates that myxozoans lack key elements of signaling pathways and transcriptional factors important for multicellular development. Our results suggest that the degeneration of the myxozoan body plan from a free-living cnidarian to a microscopic parasitic cnidarian was accompanied by extreme reduction in genome size and gene content.

Diversity and evolution of myxozoan minicollagens and nematogalectins.

BACKGROUND: Myxozoa are a diverse group of metazoan parasites with a very simple organization, which has for decades eluded their evolutionary origin. Their most prominent and characteristic feature is the polar capsule: a complex intracellular structure of the myxozoan spore, which plays a role in host infection. Striking morphological similarities have been found between myxozoan polar capsules and nematocysts, the stinging structures of cnidarians (corals, sea anemones and jellyfish) leading to the suggestion that Myxozoa and Cnidaria share a more recent common ancestry. This hypothesis has recently been supported by phylogenomic evidence and by the identification of a nematocyst specific minicollagen gene in the myxozoan Tetracapsuloides bryosalmonae. Here we searched genomes and transcriptomes of several myxozoan taxa for the presence of additional cnidarian specific genes and characterized these genes within a phylogenetic context. RESULTS: Illumina assemblies of transcriptome or genome data of three myxozoan species (Enteromyxum leei, Kudoa iwatai, and Sphaeromyxa zaharoni) and of the enigmatic cnidarian parasite Polypodium hydriforme (Polypodiozoa) were mined using tBlastn searches with nematocyst-specific proteins as queries. Several orthologs of nematogalectins and minicollagens were identified. Our phylogenetic analyses indicate that myxozoans possess three distinct minicollagens. We found that the cnidarian repertoire of nematogalectins is more complex than previously thought and we identified additional members of the nematogalectin family. Cnidarians were found to possess four nematogalectin/ nematogalectin-related genes, while in myxozoans only three genes could be identified. CONCLUSIONS: Our results demonstrate that myxozoans possess a diverse array of genes that are taxonomically restricted to Cnidaria. Characterization of these genes provide compelling evidence that polar capsules and nematocysts are homologous structures and that myxozoans are highly degenerate cnidarians. The diversity of minicollagens was higher than previously thought, with the presence of three minicollagen genes in myxozoans. Our phylogenetic results suggest that the different myxozoan sequences are the results of ancient divergences within Cnidaria and not of recent specializations of the polar capsule. For both minicollagen and nematogalectin, our results show that myxozoans possess less gene copies than their cnidarian counter parts, suggesting that the polar capsule gene repertoire was simplified with their reduced body plan.

The genome of the colonial hydroid Hydractinia reveals their stem cells utilize a toolkit of evolutionarily shared genes 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 Hydractinia's 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 Hydractinia's 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.

The Phylogenetic Position of the Enigmatic, Polypodium hydriforme (Cnidaria, Polypodiozoa): Insights from Mitochondrial Genomes.

Polypodium hydriforme is an enigmatic parasite that belongs to the phylum Cnidaria. Its taxonomic position has been debated: whereas it was previously suggested to be part of Medusozoa, recent phylogenomic analyses based on nuclear genes support the view that P. hydriforme and Myxozoa form a clade called Endocnidozoa. Medusozoans have linear mitochondrial (mt) chromosomes, whereas myxozoans, as most metazoan species, have circular chromosomes. In this work, we determined the structure of the mt genome of P. hydriforme, using Illumina and Oxford Nanopore Technologies reads, and showed that it is circular. This suggests that P. hydriforme is not nested within Medusozoa, as this would entail linearization followed by recirculation. Instead, our results support the view that P. hydriforme is a sister clade to Myxozoa, and mt linearization in the lineage leading to medusozoans occurred after the divergence of Myxozoa + P. hydriforme. Detailed analyses of the assembled P. hydriforme mt genome show that: (1) it is encoded on a single circular chromosome with an estimated size of ∼93,000 base pairs, making it one of the largest metazoan mt genomes; (2) around 78% of the genome encompasses a noncoding region composed of several repeat types; (3) similar to Myxozoa, no mt tRNAs were identified; (4) the codon TGA is a stop codon and does not encode for tryptophan as in other cnidarians; (5) similar to myxozoan mt genomes, it is extremely fast evolving.

Nonclonal coloniality: Genetically chimeric colonies through fusion of sexually produced polyps in the hydrozoan Ectopleura larynx.

Hydrozoans typically develop colonies through asexual budding of polyps. Although colonies of Ectopleura are similar to other hydrozoans in that they consist of multiple polyps physically connected through continuous epithelia and shared gastrovascular cavity, Ectopleura larynx does not asexually bud polyps indeterminately. Instead, after an initial phase of limited budding in a young colony, E. larynx achieves its large colony size through the aggregation and fusion of sexually (nonclonally) produced polyps. The apparent chimerism within a physiologically integrated colony presents a potential source of conflict between distinct genetic lineages, which may vary in their ability to access the germline. To determine the extent to which the potential for genetic conflict exists, we characterized the types of genetic relationships between polyps within colonies, using a RAD-Seq approach. Our results indicate that E. larynx colonies are indeed comprised of polyps that are clones and sexually reproduced siblings and offspring, consistent with their life history. In addition, we found that colonies also contain polyps that are genetically unrelated, and that estimates of genome-wide relatedness suggests a potential for conflict within a colony. Taken together, our data suggest that there are distinct categories of relationships in colonies of E. larynx, likely achieved through a range of processes including budding, regeneration, and fusion of progeny and unrelated polyps, with the possibility for a genetic conflict resolution mechanism. Together these processes contribute to the reevolution of the ecologically important trait of coloniality in E. larynx.