Evolution of Recombination and Genome Structure
The unique selective pressures and functional constraints that vertebrate lineages have experienced over deep evolutionary time have resulted in a diversity of different mechanisms that mediate recombination (meiotic and mitotic), gene duplication, and the evolution of novel functional elements and developmental mechanisms. I am generally interested in understanding how vertebrate genomes evolve at the molecular level and how these changes contribute to the evolution of development. Ongoing studies take advantage of the deep evolutionary history of key vertebrate groups (including lamprey and salamander) in order to better understand how novel genomic functions arise and contribute to an organism’s biology. My current research can be broken into several overlapping areas:

1) Developmentally programmed rearrangement of the lamprey genome

2) Comparative genomics of vertebrate regeneration
3) Deep evolution and rearrangement of vertebrate genome structure
4) Evolution of recombinational variation and sex-chromosomes

Developmentally Programmed Genome Rearrangements This line of research is focused on the discovery and characterization of programmed genome rearrangement events that occur during early embryogenesis in the lamprey (Petromyzon marinus). Somatic genome rearrangement is often a cause and consequence of cancers or other “genomic disorders”. However, a few metazoan and protist lineages are known to undergo tightly-regulated and large-scale somatic deletions of DNA during the normal course of their development. Our discovery of programmed genome rearrangement in lamprey (a vertebrate) fills an important gap in our understanding of dysregulated rearrangement of vertebrate genomes and the capacity for tight regulation of genome rearrangement other taxa. We have shown that programmed rearrangements result in the elimination of hundreds of millions of base pairs (~20% of the genome) from many somatic cell lineages during embryonic development. Embryological studies reveal that many of these rearrangements take place early in development, resulting in a situation wherein an individual’s “germline” and “somatic” cell lineages differ substantially in genome structure and gene content. Genomic regions that are removed via programmed rearrangements include hundreds of genes, many of which are transcribed in adult and juvenile testes or during early embryonic development. A large fraction of these germline-specific (i.e. somatically-deleted) genes have homologs that are known to contribute to genome stability or the specification and maintenance of pluripotent cell lineages. Studies of programmed genome rearrangement in lamprey can therefore provide unique insight into several critical areas of biological inquiry, including: regulation of recombination in vertebrate genomes, carcinogenesis, and the genetics of pluripotency.

Comparative Genomics of Vertebrate Regeneration Several vertebrate species have evolved, or retain, a capacity to regenerate injured tissues an organs. We are engaged in several collaborative studies that use comparative genomic analyses to identify genes and molecular pathways that contribute to regeneration. Ongoing work includes studies of regeneration in salamander, lamprey and spiny mouse.

Developing Genome Resources for Highly-Informative Vertebrate Genomes A second major focus of the lab is the development of genome resources for highly-informative vertebrate groups (diverse lampreys, hagfish, salamander and other vertebrate/invertebrate/plant lineages though collaborative efforts). These species provide insight into key periods in evolution and important aspects of vertebrate genome biology. We are also engages in the development of genome assemblies and comparative maps for several other uniquely informative vertebrate lineages.

    Lamprey: Lamprey diverged from the rest of the vertebrate lineage approximately 0.5 billion years ago and provides critical insight into the genome structure and developmental biology of the ancestral lineage that gave rise to all vertebrates. Moreover, it is the only vertebrate genome that is known to undergo large-scale programmed rearrangement.

    Salamander: The amphibian lineage (including salamander) diverged from all other tetrapods (legged vertebrates) approximately 300 million years ago and provides insight into the biology of the ancestral tetrapod. The salamander genome is one of the largest vertebrate genomes, but has otherwise undergone very little change in genome structure since divergence from the ancestral tetrapod lineage. Moreover, salamander possesses very recently-evolved sex determining system with sex chromosomes are in the earliest steps of an evolutionary path that is expected to result in dramatic structural divergence (i.e. the human X and Y chromosomes). The salamander genome can therefore provide numerous insights into the evolution and functionality of changes in genome size, gene order, and chromosome structure within vertebrates. We have established the first chromosome-scale genome assembly for salamander and are currently undertaking efforts to further improve the assembly and identify functionally relevant elements that contribute to regeneration and other aspects of salamander biology.

  Other Uniquely Informative Taxa: Including hagfish, coelacanth, spotted gar, newt ...

Jeramiah Smith

Department of Biology

University of Kentucky

Lexington, KY 40506

jjsmit3@uky.edu

Smith LAB Lab