1. Division of Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North C3-168, Seattle, Washington 98109, USA
2. Department of Bioengineering, University of Washington, Box 357962, Seattle, Washington 98195-7962, USA
3. Department of Genome Sciences, University of Washington, Box 357730, Seattle, Washington 98195-7730, USA
4. †Present address: Departments of Laboratory Medicine and Medicine (Division of Medical Genetics), University of Washington, Seattle, Washington 98195, USA

Correspondence to: Barbara J. Trask^1,2,3 Correspondence and requests for materials should be addressed to B.J.T. (Email: btrask@fhcrc.org).

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.

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