The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2

Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Genome Research (Impact Factor: 14.63). 03/2012; 22(6):1036-49. DOI: 10.1101/gr.136556.111
Source: PubMed


Chimpanzee and gorilla chromosomes differ from human chromosomes by the presence of large blocks of subterminal heterochromatin thought to be composed primarily of arrays of tandem satellite sequence. We explore their sequence composition and organization and show a complex organization composed of specific sets of segmental duplications that have hyperexpanded in concert with the formation of subterminal satellites. These regions are highly copy number polymorphic between and within species, and copy number differences involving hundreds of copies can be accurately estimated by assaying read-depth of next-generation sequencing data sets. Phylogenetic and comparative genomic analyses suggest that the structures have arisen largely independently in the two lineages with the exception of a few seed sequences present in the common ancestor of humans and African apes. We propose a model where an ancestral human-chimpanzee pericentric inversion and the ancestral chromosome 2 fusion both predisposed and protected the chimpanzee and human genomes, respectively, to the formation of subtelomeric heterochromatin. Our findings highlight the complex interplay between duplicated sequences and chromosomal rearrangements that rapidly alter the cytogenetic landscape in a short period of evolutionary time.


Available from: Tomas Marques-Bonet
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    • "Alpha satellite DNA is a major DNA component of these heterochromatin blocks,3–6 and other repetitive sequences are also known to be present there, such as satellite 1,6 satellite 2,7 and beta satellite.8 A well-known example of large-scale subtelomeric heterochromatin blocks in primates is that of chimpanzees and bonobos.9–12 These species, together with humans, belong to family Hominidae (hominids) and are phylogenetically closest to humans among extant species. "
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    ABSTRACT: Centromeres and telomeres of higher eukaryotes generally contain repetitive sequences, which often form pericentric or subtelomeric heterochromatin blocks. C-banding analysis of chromosomes of Azara's owl monkey, a primate species, showed that the short arms of acrocentric chromosomes consist mostly or solely of constitutive heterochromatin. The purpose of the present study was to determine which category, pericentric, or subtelomeric is most appropriate for this heterochromatin, and to infer its formation processes. We cloned and sequenced its DNA component, finding it to be a tandem repeat sequence comprising 187-bp repeat units, which we named OwlRep. Subsequent hybridization analyses revealed that OwlRep resides in the pericentric regions of a small number of metacentric chromosomes, in addition to the short arms of acrocentric chromosomes. Further, in the pericentric regions of the acrocentric chromosomes, OwlRep was observed on the short-arm side only. This distribution pattern of OwlRep among chromosomes can be simply and sufficiently explained by assuming (i) OwlRep was transferred from chromosome to chromosome by the interaction of pericentric heterochromatin, and (ii) it was amplified there as subtelomeric heterochromatin. OwlRep carries several direct and inverted repeats within its repeat units. This complex structure may lead to a higher frequency of chromosome scission and may thus be a factor in the unique distribution pattern among chromosomes. Neither OwlRep nor similar sequences were found in the genomes of the other New World monkey species we examined, suggesting that OwlRep underwent rapid amplification after the divergence of the owl monkey lineage from lineages of the other species.
    DNA Research 06/2013; 20(5). DOI:10.1093/dnares/dst023 · 5.48 Impact Factor
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    • "These studies point to a completely independent evolution of caps in chimpanzee and gorilla and may explain the emergence of large blocks of telomere-like repeated sequences only in the latter. Intriguingly, no interspersed blocks of telomere repeats were reported in sequencing analyses of gorilla BAC clones (19,20). Of note, however, the authors do report that 30% of the BACs completely failed to assemble or else assembled into sequence contigs substantially shorter than the expected length, indicating particular difficulties in sub-cloning and in in silico sequence assembly procedures of these regions (19,20), a difficulty perhaps enhanced by the presence of long tracks of telomere-like repeats. "
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    ABSTRACT: In contrast with the limited sequence divergence accumulated after separation of higher primate lineages, marked cytogenetic variation has been associated with the genome evolution in these species. Studying the impact of such structural variations on defined molecular processes can provide valuable insights on how genome structural organization contributes to organismal evolution. Here, we show that telomeres on chromosome arms carrying subtelomeric heterochromatic caps in the chimpanzee, which are completely absent in humans, replicate later than telomeres on chromosome arms without caps. In gorilla, on the other hand, a proportion of the subtelomeric heterochromatic caps present in most chromosome arms are associated with large blocks of telomere-like sequences that follow a replication program different from that of bona fide telomeres. Strikingly, telomere-containing RNA accumulates extrachromosomally in gorilla mitotic cells, suggesting that at least some aspects of telomere-containing RNA biogenesis have diverged in gorilla, perhaps in concert with the evolution of heterochromatic caps in this species.
    Nucleic Acids Research 03/2013; 41(9). DOI:10.1093/nar/gkt169 · 9.11 Impact Factor
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    ABSTRACT: The siamang (Symphalangus syndactylus), a species of the family Hylobatidae (gibbons), carries large blocks of constitutive heterochromatin in the telomere region of chromosomes. We recently found that alpha satellite DNA constitutes these heterochromatin blocks as a main component. Alpha satellite DNA, tandem repeat sequences of 171-bp repeat units, is a major component of centromeres in primates. In addition to the siamang, the white-cheeked gibbon (Nomascus leucogenys) was previously found to carry the alpha satellite DNA in the telomere region, although not as large a scale as the siamang. Gibbons comprise four genera: Hoolock, Hylobates, Nomascus, and Symphalangus. Here, we report that the amplification of alpha satellite DNA in the telomere region is probably confined to two genera: Nomascus and Symphalangus. We examined one species of Hoolock and four species of Hylobates and obtained evidence against such an amplification event in these species. The phylogenetic relationship of the four gibbon genera remains unclear. One simple explanation for the current distribution of the telomere region alpha satellite DNA would be that Nomascus and Symphalangus are relatively closely related and the amplification occurred in their common ancestor.
    Genome 11/2012; 55(11):809-12. DOI:10.1139/gen-2012-0123 · 1.42 Impact Factor
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