The analysis of variation at the human Xp:Yp telomere.

The DNA immediately flanking the human Xp:Yp telomere exhibits a high level of sequence polymorphism and strong linkage disequilibrium, resulting in a limited number of highly diverged haplotypes. The sequence divergence suggests that these haplotypes are ancient. Orthologous sequences in chimpanzees and gorillas are more diverged than between synonymous sequences at other loci. Balancing selection may have contributed to the maintenance of the highly diverged haplotypes flanking the human Xp:Yp telomere and may explain the high sequence divergence in closely related species. A system has been developed to assay the distribution of telomere and variant repeats within the proximal 120 repeats of Xp:Yp telomeres to create a telomere map. The distributions of these repeats is highly polymorphic with estimated heterozygosities in excess of 99%. The mutation rate underlying this variation was measured directly as 6.25x10.;-3 per gamete. Alleles were grouped by similarities in their telomeremaps, these groups of alleles also share the same haplotype in the telomere flanking DNA. This suggests that these alleles have evolved along haploid lineages and that the predominant mutational mechanisms influencing the evolution of sequences at the proximal end of this telomere must be of an intra-allelic nature. Comparison of alleles suggests that most of the differences could be accounted for by small localised replication-slippage like events. Analysis of the chimpanzee and gorilla sequences orthologous to the human Xp:Yp telomere revealed that a telomere was not present at the same location in these species. Instead, two small interstitial blocks of telomere-like repeats were present in gorilla and an array of chimpanzee and gorilla specific subterminal satellite was present in chimpanzees. Therefore, the location of the Xp:Yp telomere is unique to the human lineage and may therefore be relatively new in evolutionary terms.