Detecting adaptive changes in gene copy number distribution accompanying the human out-of-Africa expansion

Abstract

Genes with multiple copies are likely to be maintained by stabilizing selection that puts a bound to unlimited expansion of copy number. We designed a model where copy number variation is generated by unequal recombination, which fits well to a number of genes, surveyed in three human populations. Based on this theoretical model and on computer simulations, we were interested in answering the question whether gene copy number distribution in the derived European and Asian populations can be explained by a purely demographic scenario or whether shifts in the distribution are signatures of adaptation. Although copy number distribution in most of the analyzed gene clusters can be explained by a bottleneck as in the out of Africa expansion of homo sapiens 60-10kyrs ago, we identified several candidate genes, for instance AMY1A and PGA3, whose copy numbers are likely to be selected differently among African, Asian and European populations.