The evolution of African great ape subtelomeric heterochromatin and the fusion of human chromosome 2.
ABSTRACT 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.
Article: The high variability of subtelomeric heterochromatin and connections between nonhomologous chromosomes, suggest frequent ectopic recombination in rye meiocytes.[show abstract] [hide abstract]
ABSTRACT: The position of telomeres, centromeres and subtelomeric heterochromatin (SH) has been studied by FISH in rye meiocytes. We compare the morphology of the signals from zygotene to telophase II mainly to determine differences in SH and telomere positions between plants with and without neocentromeres. Plants from two varieties were used: Paldang showing neocentromeres, and Puyo without neocentromeres but with two B chromosomes. In both varieties, at zygotene and pachytene the SH is observed forming clumps often including two or more bivalent ends. At diplotene the SH is stretched suggesting that it is close to the nuclear envelope. In these cases, the telomere signals are not stretched and lay behind the SH. Frequently, two or more bivalents are joined by conspicuous SH connections at diplotene strongly suggesting ectopic recombination. Probably as a result, differential distribution of the SH between recombinant homologues or the whole meiotic products is observed. From diplotene onwards, the large heterochromatic blocks cover the telomeres, the SH being the morphological end of the bivalents, both in plants with or without neocentromeres. The Bs are tightly associated only at the telomeric end of the long arm from diplotene to metaphase I. The high variability between homologous chromosomes and the frequent nonhomologous bindings of SH, strongly suggest that rye SH is in dynamic state and frequently changes in chromosome position during meiosis.Cytogenetic and Genome Research 02/2006; 115(2):179-85. · 1.53 Impact Factor
Article: Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication[show abstract] [hide abstract]
ABSTRACT: Human subtelomeres are polymorphic patchworks of interchromosomal segmental duplications at the ends of chromosomes. Here we provide evidence that these patchworks arose recently through repeated translocations between chromosome ends. We assess the relative contribution of the principal mechanisms of ectopic DNA repair to the formation of subtelomeric duplications and find that non-homologous end-joining predominates. Once subtelomeric duplications arise, they are prone to homology-based sequence transfers as shown by the incongruent phylogenetic relationships of neighbouring sections. Interchromosomal recombination of subtelomeres is a potent force for recent change. Cytogenetic and sequence analyses reveal that pieces of the subtelomeric patchwork have changed location and copy number with unprecedented frequency during primate evolution. Half of the known subtelomeric sequence has formed recently, through human-specific sequence transfers and duplications. Subtelomeric dynamics result in a gene duplication rate significantly higher than the genome average and could have both advantageous and pathological consequences in human biology. More generally, our analyses suggest an evolutionary cycle between segmental polymorphisms and genome rearrangements.Nature 08/2005; 437(7055):94-100. · 36.28 Impact Factor
Article: Chromosome heteromorphisms in the gorilla karyotype. Analyses with distamycin A/DAPI, quinacrine and 5-azacytidine.[show abstract] [hide abstract]
ABSTRACT: The chromosomes of one male and three female gorillas were extensively studied with various regional banding methods. The chromosomes were stained with the fluorescent dyes quinacrine mustard and distamycin A/DAPI (DA/DAPI), which label different subsets of heterochromatin in the chromosome complement. Furthermore, lymphocyte cultures were treated with the cytidine analog 5-azacytidine (5-azaC). The 5-azaC-induced undercondensations were found in most of the DA/DAPI-bands as well as in many telomeric C-bands. The karyotype of the gorilla exhibits a considerable number of heterochromatin variants. Of the different types of heteromorphisms noted, the most striking is that involving the short arm regions of chromosomes 12 to 16 and 23 (satellite stalk regions) and the paracentromeric heterochromatin of chromosomes 17 and 18. There also are numerous heteromorphic C-bands localized in the telomeric regions of homologous chromosome arms. In comparison, only few heteromorphisms occur between C-bands in the centromeric and pericentromeric regions of homologs. Finally, a variability in the fluorescence intensity of quinacrine-bright satellites in the short arms of chromosomes 12 to 16, 22, and 23 is observed.Journal of Heredity 78(5):287-92. · 2.80 Impact Factor