Identification of large-scale DNA copy number differences between human and non-human primate genomes and their role in mediating evolutionary rearrangements

Abstract

Comparative analysis of human and great ape genomes expose the full spectrum of genomic changes that accompanied human evolution. In particular the concomitant evaluation of divergence and diversity has the power to identify those genes or genomic regions that evolved under selective constraints during evolution and might be associated with human specialization. In order to identify copy number differences (CNDs) that occurred specifically in the human lineage, we performed interspecies aCGH including macaque, orang-utan, gorilla, chimpanzee and bonobo. By this, I was able to identify 14 sites of human specific CNDs and I could show that DNA copy number gains are not only important for gene dosage changes but that they are localized at sites of numerous large-scale rearrangements that occurred during human genome evolution. The presence of low copy repeats (LCRs) at the borders of human-specific pericentric inversions suggests their implication in mediating the respective rearrangements by allowing intrachromosomal homologous recombination between these repeats. Furthermore, the precise characterization of the breakpoints of the pericentric inversions of HSA 18 and of PTR XVI and GGO XVI allowed me to study the LCR content of the breakpoint regions of these rearrangements. I found that LCRs bordered each breakpoint, confirming the importance of segmental duplications in mediating evolutionary rearrangements. Moreover, I have determined that the pericentric inversions of PTR XVI and GGO XVI occurred twice independently during evolution verifying the instability of that region. In conclusion, my study showed that segmental duplications are frequently assigned to unstable genomic regions and to chromosomal breakpoints, emphasizing their role in determining both karyotypic evolution and genomic diversity in humans