Recent Segmental Duplications and the Fragile Breakage Model of Human Genome Evolution

Friday, October 24, 2003 - 1:30pm - 2:20pm
Keller 3-180
Evan Eichler (Case Western Reserve University)
It has been estimated that 5% of the human genome consists of interspersed duplicated material that has arisen over the last 30-40 million years of evolution. A large proportion of these duplications exhibits an extraordinarily high degree of sequence identity at the nucleotide level (>95%) and are interspersed over large genomic distances (>1 Mb). The distribution of these duplications is non-random in the human genome. Through processes of non-allelic homologous recombination, these same regions are targets for rapid evolutionary turnover creating hotspots of mammalian chromosomal evolution and sites of genomic instability associated with disease within the human population. Preliminary analyses have suggested that the amount of segmental duplication may be a relatively unique property of our genome. We have developed systematic experimental and computational tools to examine duplication content from human and other sequenced vertebrate species. An analysis of the breakpoints of these duplications shows a significant enrichment of Alu-repeat elements, providing new insight into their mechanism of origin and preeminence within the primate genome. In additions based on our analysis of syntenic breakpoints between the mouse and human genome, we find that 25% (122/461) of mouse-human synteny breakpoints contain 10 kb of duplicated sequence. This association is highly significant (P