A satellite-like sequence, representing a "clone gap" in the human genome, was likely involved in the seeding of a novel centromere in macaque.

Although the human genome sequence is generally considered "finished", the latest assembly (NCBI Build 36.1) still presents a number of gaps. Some of them are defined as "clone gaps" because they separate neighboring contigs. Evolutionary new centromeres are centromeres that repositioned along the chromosome, without marker order variation, during evolution. We have found that one human "clone gap" at 18q21.2 corresponds to an evolutionary new centromere in Old World Monkeys (OWM). The partially sequenced gap revealed a satellite-like structure. DNA stretches of the same satellite were found in the macaque (flanking the chromosome 18 centromere) and in the marmoset (New World Monkey), which was used as an outgroup. These findings strongly suggested that the repeat was present at the time of novel centromere seeding in OWM ancestor. We have provided, therefore, the first instance of a specific sequence hypothesized to have played a role in triggering the emergence of an evolutionary new centromere.

Evolutionary history of chromosome 11 featuring four distinct centromere repositioning events in Catarrhini.

Panels of BAC clones used in FISH experiments allow a detailed definition of chromosomal marker arrangement and orientation during evolution. This approach has disclosed the centromere repositioning phenomenon, consisting in the activation of a novel, fully functional centromere in an ectopic location, concomitant with the inactivation of the old centromere. In this study, appropriate panels of BAC clones were used to track the chromosome 11 evolutionary history in primates and nonprimate boreoeutherian mammals. Chromosome 11 synteny was found to be highly conserved in both primate and boreoeutherian mammalian ancestors. Amazingly, we detected four centromere repositioning events in primates (in Old World monkeys, in gibbons, in orangutans, and in the Homo-Pan-Gorilla (H-P-G) clade ancestor), and one in Equidae. Both H-P-G and Lar gibbon novel centromeres were flanked by large duplicons with high sequence similarity. Outgroup species analysis revealed that this duplicon was absent in phylogenetically more distant primates. The chromosome 11 ancestral centromere was probably located near the HSA11q telomere. The domain of this inactivated centromere, in humans, is almost devoid of segmental duplications. An inversion occurred in chromosome 11 in the common ancestor of H-P-G. A large duplicon, again absent in outgroup species, was found located adjacent to the inversion breakpoints. In Hominoidea, almost all the five largest duplicons of this chromosome appeared involved in significant evolutionary architectural changes.