Population dynamics-coded in DNA: genetic traces of the expansion of modemhumans

It has been proposed that modern humans evolved from a small ancestral popu lation, which appeared several hundred thousand years ago in Africa. Descen dants of the founder group migrated to Europe and then to Asia, not mixing with the pre-existing local populations but replacing them. Two demographic elements are present in this "out of Africa" hypothesis: numerical growth of the modem humans and their migration into Eurasia. Did these processes l eave an imprint in our DNA? To address this question, we use the classical Fisher-Wright-Moran model of population genetics, assuming variable populat ion size and two models of mutation: the infinite-sites model and the stepw ise-mutation model. We use the coalescence theory, which amounts to tracing the common ancestors of contemporary genes. We obtain mathematical formula e expressing the distribution of alleles given the time changes of populati on size. In the framework of the infinite-sites model, simulations indicate that the pattern of past population size change leaves its signature on th e pattern of DNA polymorphism. Application of the theory to the published m itochondrial DNA sequences indicates that the current mitochondrial DNA seq uence variation is not inconsistent with the logistic growth of the modem h uman population. In the framework of the stepwise-mutation model, we demons trate that population bottleneck followed by growth in size causes an imbal ance between allele-size variance-and heterozygosity, We analyze a set of d ata on tetranucleotide repeats which reveals the existence of this imbalanc e. The pattern of imbalance is consistent with the bottleneck being most an cient in Africans, most recent in Asians and intermediate in Europeans. The se findings are consistent with the "out of Africa" hypothesis, although by no means do they constitute its proof. (C) 1999 Elsevier Science B.V. All rights reserved.