Progressive proximal expansion of the primate X chromosome centromere

Abstract

Previous studies of the pericentromeric region of the human X chromosome short arm (Xp) revealed an age gradient from ancient DNA that contains expressed genes to recent human-specific DNA at the functional centromere. We analyzed the finished sequence of this human genomic region to investigate its evolutionary history. Phylogenetic analysis of >1,500 alpha-satellite monomers from the region revealed the presence of five physical domains, each containing monomers from a distinct phylogenetic clade. The most distal domain contains long interspersed nucleotide element repeats that were active >35 million years ago, whereas the four proximal domains contain more recently active long interspersed nucleotide element repeats. An out-of-register, unequal recombination (i.e., crossover) detected at the edge of the X chromosomespecific alpha-satellite array (DXZ1) may reflect the most recent of a series of punctuating events during evolution that resulted in a proximal physical expansion of the X centromere. The first 18 kb of this array has 97-99% pairwise identity among all 2-kb repeat units. To perform more detailed evolutionary comparisons, we sequenced the junction between the ancient DNA of Xp and the primate-specific alpha satellite in chimpanzee, gorilla, orangutan, vervet, macaque, and baboon. The striking conservation found in all cases supports the ancestral nature of the alpha satellite at this location. These studies demonstrate that the primate X centromere appears to have evolved through repeated expansion events occurring within the central, active region of centromeric DNA, with the newly added sequences then conferring centromere function.evolution ͉ alpha satellite ͉ comparative genomics ͉ genome sequencing

Clusters of alpha satellite on human chromosome 21 are dispersed far onto the short arm and lack ancient layers

“…This model for AS evolution is supported by studies of the detailed organization of AS clusters on chromosomes X, 8 and 17 (Schueler et al 2001, Schueler et al 2005, Rudd et al 2006, Shepelev et al 2009). In all cases the HOR-containing functional centromere is surrounded by multiple monomeric AS clusters arrayed roughly symmetrically on both chromosome arms.…”

Human centromere genomics: now it's personal

“…In contrast, monomeric regions provide adequate sequence variation for standard overlap alignment and therefore represent the majority of alpha satellite sequences included in the human reference assembly (Rudd and Willard 2004;She et al 2004). Genomic studies of the annotated monomeric regions adjacent to centromere-assigned gaps on chromosomes X, 8, and 17 in the human reference assembly provide evidence for phylogenetically defined "blocks" of divergent satellite sequences that appear to gradually shift away from the homogenized array (Schueler et al 2005(Schueler et al , 2001Shepelev et al 2009). This specialized form of sequence evolution has also been monitored by regional patterns of transposable element insertions, as LINE are documented to increase in number and molecular dating when distanced from the homogenized HOR array (Schueler et al 2005(Schueler et al , 2001).…”

“…Genomic studies of the annotated monomeric regions adjacent to centromere-assigned gaps on chromosomes X, 8, and 17 in the human reference assembly provide evidence for phylogenetically defined "blocks" of divergent satellite sequences that appear to gradually shift away from the homogenized array (Schueler et al 2005(Schueler et al , 2001Shepelev et al 2009). This specialized form of sequence evolution has also been monitored by regional patterns of transposable element insertions, as LINE are documented to increase in number and molecular dating when distanced from the homogenized HOR array (Schueler et al 2005(Schueler et al , 2001). Even at the short transition between monomeric and HOR repeats, increased levels of HOR repeat divergence are observed, thus promoting a generally accepted model of alpha satellite sequence evolution where array turnover and satellite variant innovation and expansion promote displacement and divergence of those sequences at the edge of the array (Schueler et al 2005;Shepelev et al 2009).…”

“…This specialized form of sequence evolution has also been monitored by regional patterns of transposable element insertions, as LINE are documented to increase in number and molecular dating when distanced from the homogenized HOR array (Schueler et al 2005(Schueler et al , 2001). Even at the short transition between monomeric and HOR repeats, increased levels of HOR repeat divergence are observed, thus promoting a generally accepted model of alpha satellite sequence evolution where array turnover and satellite variant innovation and expansion promote displacement and divergence of those sequences at the edge of the array (Schueler et al 2005;Shepelev et al 2009). …”

“…Sequence assembly within the X centromeric region currently represents the monomeric to higherorder transition from both p arm and q arm, linking both sides to a single HOR array (DXZ1) defined by a 12-monomer repeat unit Schueler et al 2005Schueler et al , 2001. Physical maps and direct sequencing across DXZ1 reveal that the centromeric gap can be defined as a multi-megabase array with limited pairwise sequence divergence (~1-2 %) to differentiate HOR repeats (Durfy and Willard 1989).…”