Breakpoint analysis of the pericentric inversion between chimpanzee chromosome 10 and the homologous chromosome 12 in humans

Abstract

During this study, we analysed the pericentric inversion that distinguishes human chromosome 12 (HSA12) from the homologous chimpanzee chromosome (PTR10). Two large chimpanzee-specific duplications of 86 and 23 kb were observed in the breakpoint regions, which most probably occurred associated with the inversion. The inversion break in PTR10p caused the disruption of the SLCO1B3 gene in exon 11. However, the 86-kb duplication includes the functional SLCO1B3 locus, which is thus retained in the chimpanzee, although inverted to PTR10q. The second duplication spans 23 kb and does not contain expressed sequences. Eleven genes map to a region of about 1 Mb around the breakpoints. Six of these eleven genes are not among the differentially expressed genes as determined previously by comparing the human and chimpanzee transcriptome of fibroblast cell lines, blood leukocytes, liver and brain samples. These findings imply that the inversion did not cause major expression differences of these genes. Comparative FISH analysis with BACs spanning the inversion breakpoints in PTR on metaphase chromosomes of gorilla (GGO) confirmed that the pericentric inversion of the chromosome 12 homologs in GGO and PTR have distinct breakpoints and that humans retain the ancestral arrangement. These findings coincide with the trend observed in hominoid karyotype evolution that humans have a karyotype close to an ancestral one, while African great apes present with more derived chromosome arrangements.

A genome-wide survey of structural variation between human and chimpanzee

“…(Yunis et al 1980;Yunis and Prakash 1982). The breakpoints depicted map within 40 kb of recently characterized sequence breakpoints (Kehrer-Sawatzki et al 2005b). A second "putative" inversion shown on chromosome 12 is due to a lineage-specific transposition of a segmental duplication in the chimpanzee genome.…”

Comprehensive Analyses of White-Handed Gibbon Chromosomes Enables Access to 92 Evolutionary Conserved Breakpoints Compared to the Human Genome

“…The possible mechanisms responsible for such an increased genome evolution might be due to LAVA (gibbon specific retrotransposon)-induced premature transcription termination of chromosome segregation genes [Carbone et al, 2014]. Pericentric inversions are considered to be the most common euchromatic chromosomal differences between humans and the great apes [Nickerson and Nelson, 1998;Locke et al, 2003, Kehrer-Sawatzki et al, 2005. According to fig.…”

Molecular cytogenetic and genomic insights into chromosomal evolution

“…Although reasons for these differences in tempo are still unclear, making this one of the most puzzling aspects of comparative cytogenetics, a burgeoning literature has identified regions at the junctions of synteny blocks that are rich in segmental duplications (Bailey and Eichler, 2006;Carbone et al, 2006;Kehrer-Sawatzki and Cooper, 2008), repeat content (Kehrer-Sawatzki et al, 2005;RuizHerrera et al, 2006) and transposable elements (Bourque, 2009;Carbone et al, 2009;Delprat et al, 2009;Longo et al, 2009), predisposing these regions to rearrangement. In addition, transposable element activity and changes in DNA methylation patterns have been suggested as having a causative role in the structural modification of genomes in species as diverse as marsupials, rodents and primates (O'Neill et al, 1998;Brown et al, 2002;Carbone et al, 2009).…”