Adaptive evolution of UGT2B17 copy-number variation

Am J Hum Genet. 2008 Sep;83(3):337-46. doi: 10.1016/j.ajhg.2008.08.004. Epub 2008 Aug 28.

Abstract

The human UGT2B17 gene varies in copy number from zero to two per individual and also differs in mean number between populations from Africa, Europe, and East Asia. We show that such a high degree of geographical variation is unusual and investigate its evolutionary history. This required first reinterpreting the reference sequence in this region of the genome, which is misassembled from the two different alleles separated by an artifactual gap. A corrected assembly identifies the polymorphism as a 117 kb deletion arising by nonallelic homologous recombination between approximately 4.9 kb segmental duplications and allows the deletion breakpoint to be identified. We resequenced approximately 12 kb of DNA spanning the breakpoint in 91 humans from three HapMap and one extended HapMap populations and one chimpanzee. Diversity was unusually high and the time to the most recent common ancestor was estimated at approximately 2.4 or approximately 3.0 million years by two different methods, with evidence of balancing selection in Europe. In contrast, diversity was low in East Asia where a single haplotype predominated, suggesting positive selection for the deletion in this part of the world.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Evolution*
  • Gene Dosage*
  • Genetic Variation*
  • Genetics, Population*
  • Glucuronosyltransferase / genetics*
  • Humans
  • Minor Histocompatibility Antigens
  • Pan troglodytes / genetics
  • Racial Groups / genetics
  • Sequence Deletion

Substances

  • Minor Histocompatibility Antigens
  • Glucuronosyltransferase
  • UGT2B17 protein, human