A cascade of complex subtelomeric duplications during the evolution of thehominoid and old world monkey genomes

Subtelomeric duplications of an obscure tubulin "genic" segment located nea r the telomere of human chromosome 4q35 have occurred at different evolutio nary time points within the last 25 million years of the catarrhine (i.e., hominoid and Old World monkey) evolution. The analyses of these segments re ported here indicate an exceptional level of evolutionary instability. Subs tantial intra- and interspecific differences in copy number and distributio n are observed among cercopithecoid (Old World monkey) and hominoid genomes . Characterization of the hominoid duplicated segments reveals a strong pos itional bias within pericentromeric and subtelomeric regions of the genome. On the basis of phylogenetic analysis from predicted proteins and comparis ons of nucleotide-substitution rates, we present evidence of a conserved b- tubulin gene among the duplications. Remarkably, the evolutionary conservat ion has occurred in a nonorthologous fashion, such that the functional copy has shifted its positional context between hominoids and cercopithecoids. We propose that, in a chimpanzee-human common ancestor, one of the paralogo us copies assumed the original function, whereas the ancestral copy acquire d mutations and eventually became silenced. Our analysis emphasizes the dyn amic nature of duplication-mediated genome evolution and the delicate balan ce between gene acquisition and silencing.