Evidence for positive selection and population structure at the human MAO-A gene

Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):862-7. doi: 10.1073/pnas.022614799.


We report the analysis of human nucleotide diversity at a genetic locus known to be involved in a behavioral phenotype, the monoamine oxidase A gene. Sequencing of five regions totaling 18.8 kb and spanning 90 kb of the monoamine oxidase A gene was carried out in 56 male individuals from seven different ethnogeographic groups. We uncovered 41 segregating sites, which formed 46 distinct haplotypes. A permutation test detected substantial population structure in these samples. Consistent with differentiation between populations, linkage disequilibrium is higher than expected under panmixia, with no evidence of a decay with distance. The extent of linkage disequilibrium is not typical of nuclear loci and suggests that the underlying population structure may have been accentuated by a selective sweep that fixed different haplotypes in different populations, or by local adaptation. In support of this suggestion, we find both a reduction in levels of diversity (as measured by a Hudson-Kreitman-Aguade test with the DMD44 locus) and an excess of high frequency-derived variants, as expected after a recent episode of positive selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Genetic Variation
  • Genetics, Behavioral
  • Genetics, Population
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Monoamine Oxidase / genetics*
  • Pan troglodytes
  • Recombination, Genetic
  • Selection, Genetic*


  • Monoamine Oxidase