Reconstructing the Biology of Ancestral Vertebrate Genomes

Grants and Contracts Details


Overview - The common ancestor of all extant vertebrates lived approximately 600 million years ago (MYA), during the late Precambrian. The diverse biologies of all living vertebrate lineages were built upon the foundation of this ancestral lineage and reflect conservation and change over eons of evolution. Recognizing the need to better understand this evolutionary foundation, a handful of genome projects have been initiated that target deep vertebrate lineages (e.g. sharks and lampreys). These projects have provided critical perspective on the evolution of genome structure, yet our understanding of ancestral genome biology has changed dramatically as each new assembly has come on line. For example, several of deeply diverged vertebrate lineages have been found to undergo programmed genome rearrangements (PGRs) that differentiate their germline and somatic genomes (including hagfish, lampreys and some lineages of cartilaginous fish). While these studies have revolutionized our understanding of vertebrate genome biology, they also illustrate the importance of extending these studies to include information from other deep vertebrate lineages. Proposed studies will leverage several analytical approaches that were recently developed for lamprey, in order to more accurately reconstruct the ancestry and evolution of vertebrate genome biology. First, highly contiguous genome assemblies will be generated for several taxa that strategically fill large sampling gaps in the tree of life (two sharks, two hagfish and three lampreys). Chromosome-scale scaffolding of these assemblies will employ a single-sperm sequencing approach that permits the development of dense linkage maps for species that are not amenable to laboratory culture. Resulting assemblies will permit more accurate reconstructions of the physical structure and gene content of the vertebrate ancestor and the ancestors of all major vertebrate lineages. Second, comparative sequencing of DNA from germline and somatic tissues will be performed in order to assay for PGR in these lineages and shed light on the origin(s) of PGR and the evolution of sequences that are targeted for elimination. Finally, comparative embryological methods and bisulfite sequencing will be used to characterize patterns of DNA methylation and test the emerging hypothesis that programmed genome rearrangement is mechanistically tied to fundamental silencing events that occur during the earliest stages of vertebrate development. Intellectual Merit - The proposed research has the potential to significantly add to our understanding of the ancestry and evolution of vertebrate genomes, both in terms of the evolution of genome structure/content and in terms of fundamental developmental events that regulate the functionality of the genome. By targeting a specific set of highly informative species, these studies will provide robust reconstructions of vertebrate genome evolution and enable statistical analysis of alternate scenarios that explain the distribution of conserved segments and duplicated genes within vertebrate genomes. These studies will also significantly add to our understanding of the evolution of regulatory mechanisms that establish fundamental domains of gene expression during the earliest stages of embryonic development (i.e. the mid-blastula transition: MBT) by 1) extending our knowledge of phylogenetic distribution and genetic impact of PGR and 2) defining evolutionary/genetic relationships between PGR and methylation events that occur at the onset of the MBT. Broader Impacts - Data generated under all three aims will also significantly benefit research and educational communities that use the existing public genome projects for sea lamprey, elephant shark and little skate by improving assembly and annotation of these important genomes. Of equal importance is the impact that this research will have on the conservation and restoration of two lamprey species that are of critical cultural importance to the indigenous people that inhabit their native ranges (the Pacific lamprey and pouched lamprey), and biocontrol of invasive sea lamprey. Datasets generated under this proposal will also directly contribute to undergraduate, graduate and professional training in bioinformatics at the University of Kentucky and will facilitate outreach to students and underrepresented groups in the Commonwealth of Kentucky (by both training current and future teachers and directly engaging underrepresented groups) and in tribal communities of the Pacific Northwest and New Zealand.
Effective start/end date7/15/186/30/24


  • National Science Foundation: $900,000.00


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