Title

An ultra-conserved retrovirus and its impact on vertebrate genome evolution

Date of Completion

January 2008

Keywords

Biology, Virology

Degree

Ph.D.

Abstract

Critical to all eukaryotic cells, the centromere is a cytogenetically defined entity that remains enigmatic even in the post-genomic era. Through its involvement in karyotypic evolution, the sequences that influence centromere identity have impacted eukaryotic evolution in a profound way. It is therefore paradoxical that modern centromere sequences share little identity in comparison to the well-conserved proteins that bind to the centromere. ^ One class of elements found near the centromere often associated with genomic instability are transposable elements. TEs, first identified as "controlling elements" by McClintock, are persistent residents of all eukaryotic genomes. TEs have had a significant impact on the host genome in which they reside. This work specifically explores a marsupial transposable element, the kangaroo endogenous retrovirus KERV, which has shown remarkable localization predominantly to the centromeres of its host genome. This thesis explores the hypothesis that KERV has influenced the evolution of the marsupial genome through its impact on the centromere. ^ KERV was initially identified in an interspecific marsupial hybrid in which it underwent significant amplification. This amplification has been shown to be localized to the centromere of several hybrids and has even been shown to cause the formation of aberrant structures at centromeres. Cytogenetic analysis of KERV in several marsupials determined it was localized to all centromeres but also to breaks in syntenic blocks as well as telomeres. All of these cytogenetic locations were centromeres in an ancestor or are centromeres in other species. This established an association between KERV and the centromere within marsupials. ^ Characterization of KERV revealed its surprising widespread distribution amongst extant marsupials. Sequence analysis of KERV ultimately determined extensive similarity between sequences estimated to have diverged > 60mya. While such conservation is not uncommon for genic sequences, it is exceptional for transposable elements, particularly retroviruses and suggests that KERV is under purifying selection. ^ Experiments expanding this analysis within vertebrates revealed astonishing similar results. Presented herein are results detailing the ultra-conservation, consistent expression, and centromeric localization of KERV over almost half a billion years of evolution. These data provide evidence that KERV represents a conserved sequence localized to the centromeres of several vertebrate clades, in defiance of the Centromere Paradox. This research expands upon our understanding of the centromere and its evolution. Continued exploration of KERV will shed light on karyotypic and genome evolution and how transposable elements have impacted each. ^