Evolutionary breakpoints are co-localized with fragile sites and intrachromosomal telomeric sequences in primates

Abstract

The concentration of evolutionary breakpoints in primate karyotypes in some particular regions or chromosome bands suggests that these chromosome regions are more prone to breakage. This is the first extensive comparative study which investigates a possible relationship of two genetic markers (intrachromosomal telomeric sequences [TTAGGG]n, [ITSs] and fragile sites [FSs]), which are implicated in the evolutionary process as well as in chromosome rearrangements. For this purpose, we have analyzed: (a) the cytogenetic expression of aphidicolin-induced FSs in Cebus apella and Cebus nigrivittatus (F. Cebidae, Platyrrhini) and Mandrillus sphinx (F. Cercopithecidae, Catarrhini), and (b) the intrachromosomal position of telomeric-like sequences by FISH with a synthetic (TTAGGG)n probe in C. apella chromosomes. The multinomial FSM statistical model allowed us to determinate 53 FSs in C. apella, 16 FSs in C. nigrivittatus and 50 FSs in M. sphinx. As expected, all telomeres hybridized with the probe, and 55 intrachromosomal loci were also detected in the Cebus apella karyotype. The χ² test indicates that the coincidence of the location of Cebus and Mandrillus FSs with the location of human FSs is significant (P < 0.005). Based on a comparative cytogenetic study among different primate species we have identified (or described) the chromosome bands in the karyotypes of Papionini and Cebus species implicated in evolutionary reorganizations. More than 80% of these evolutionary breakpoints are located in chromosome bands that express FSs and/or contain ITSs.

The biological effects of simple tandem repeats: Lessons from the repeat expansion diseases: Table 1.

“…Deletion breakpoints map to FRA11B, a folate-sensitive fragile site, as well as to other more distal CGG•CCG-repeat tracts (Jones et al 2000). Fragile sites in primates have been shown to constitute breakpoints that have contributed to chromosome evolution (Ruiz-Herrera et al 2005, 2006. In fact, it has been suggested that mammalian chromosomal evolution has been driven by such sites and that "the human genome can be considered a mosaic comprising regions of fragility that are prone to reorganization" (Ruiz-Herrera et al 2005).…”

Tracking the complex flow of chromosome rearrangements from the Hominoidea Ancestor to extant Hylobates and Nomascus Gibbons by high-resolution synteny mapping

“…The reuse of some regions as places of "chromosomal events" like rearrangements, segmental duplications, fragile sites, and centromere repositioning has been pointed out in a number of studies (Armengol et al 2003;Pevzner and Tesler 2003;Bailey et al 2004a;Ventura et al 2004;Ruiz-Herrera et al 2005).…”

Genome rearrangements caused by interstitial telomeric sequences in yeast

“…A subset of s-ITSs in the human genome is bound by the shelterin proteins Rap1, TRF1, and TRF2 (6). In primates and rodents, s-ITSs colocalize with some of the chromosomal fragile sites (7,8) and map to chromosome breakpoints in cancer cells (9). An 800-bp s-ITS integrated into the intron of the APRT gene in Chinese hamster ovary cells substantially increased the rate of deletions and insertions (10).…”