A High-Resolution Map of Synteny Disruptions in Gibbon and Human Genomes

Abstract

Gibbons are part of the same superfamily (Hominoidea) as humans and great apes, but their karyotype has diverged faster from the common hominoid ancestor. At least 24 major chromosome rearrangements are required to convert the presumed ancestral karyotype of gibbons into that of the hominoid ancestor. Up to 28 additional rearrangements distinguish the various living species from the common gibbon ancestor. Using the northern white-cheeked gibbon (2n ¼ 52) (Nomascus leucogenys leucogenys) as a model, we created a high-resolution map of the homologous regions between the gibbon and human. The positions of 100 synteny breakpoints relative to the assembled human genome were determined at a resolution of about 200 kb. Interestingly, 46% of the gibbon-human synteny breakpoints occur in regions that correspond to segmental duplications in the human lineage, indicating a common source of plasticity leading to a different outcome in the two species. Additionally, the full sequences of 11 gibbon BACs spanning evolutionary breakpoints reveal either segmental duplications or interspersed repeats at the exact breakpoint locations. No specific sequence element appears to be common among independent rearrangements. We speculate that the extraordinarily high level of rearrangements seen in gibbons may be due to factors that increase the incidence of chromosome breakage or fixation of the derivative chromosomes in a homozygous state.

Sequencing human–gibbon breakpoints of synteny reveals mosaic new insertions at rearrangement sites

“…Gibbons are known to have a rapid rate of chromosomal evolution among the hominoids, mainly involving large-scale rearrangements and rapid karyotypic divergence (Muller et al 2003;Carbone et al 2006;Roberto et al 2007). In contrast to human and great ape segmental duplications, where ;70% of all largescale evolutionary rearrangements map to regions of segmental duplication (Kehrer-Sawatzki and Cooper 2008), initial studies of the gibbon reported that only 46% of gibbon breakpoints mapped to sites of segmental duplication in the human lineage (Carbone et al 2006).…”

“…The average breakpoint resolutions of these two studies were ;80 kbp and 200 kbp, respectively (Carbone et al 2006;Roberto et al 2007). At this level of resolution, molecular mechanisms causing synteny breaks were not clear; however, segmental duplications were estimated to be associated with 46% of the rearrangements (Carbone et al 2006).…”

“…The orthologous chromosomal blocks between human and NLE gibbon were recently mapped by two studies using bacterial artificial chromosome (BAC) end sequencing or array painting and confirmed by FISH (Carbone et al 2006;Roberto et al 2007). The average breakpoint resolutions of these two studies were ;80 kbp and 200 kbp, respectively (Carbone et al 2006;Roberto et al 2007).…”

“…Chromosomal evolution in primates has been investigated at several levels of resolution, including comparative chromosome banding (Yunis and Prakash 1982), gene mapping (Turleau et al 1983), cross-species chromosomal painting (Jauch et al 1992;Murphy et al 2005), comparative genome hybridization painting (Carbone et al 2006), and fluorescent in situ hybridization (FISH) (Wienberg 2005). In general, linkage groups, gene order, and function have remained relatively unchanged since the common catarrhine primate ancestor (Haig 1999).…”

“…Although the potential for disruption of several genes in the vicinity of the breaks was suggested, the effect of the breaks on the gene structures, per se, was not well defined at this resolution. Previously, sequencing of a subset of gibbon BAC clones revealed segmental duplications or interspersed repeats at the breakpoints, although a detailed analysis of these regions was not presented (Carbone et al 2006). While karyotypic variations are implicated for anatomical and phenotypic differences between hominoid species (Ferguson-Smith and Trifonov 2007), a highresolution comparative genomics approach is imperative to identify the underlying causative molecular event.…”