Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication

Nature. 2005 Sep 1;437(7055):94-100. doi: 10.1038/nature04029.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Chromosome Breakage / genetics
  • Chromosomes, Human / genetics*
  • Computational Biology
  • DNA Repair
  • Gene Duplication*
  • Genome, Human
  • Genomics
  • Humans
  • Models, Genetic
  • Polymorphism, Genetic / genetics
  • Primates / genetics
  • Recombination, Genetic / genetics*
  • Sequence Homology, Nucleic Acid
  • Telomere / genetics*
  • Time Factors
  • Translocation, Genetic / genetics