Human genetic diversity is shaped by both demographic and biological factors and has fundamental implications for understanding the genetic basis of diseases. We studied 938 unrelated individuals from 51 populations of the Human Genome Diversity Panel at 650,000 common single-nucleotide polymorphism loci. Individual ancestry and population substructure were detectable with very high resolution. The relationship between haplotype heterozygosity and geography was consistent with the hypothesis of a serial founder effect with a single origin in sub-Saharan Africa. In addition, we observed a pattern of ancestral allele frequency distributions that reflects variation in population dynamics among geographic regions. This data set allows the most comprehensive characterization to date of human genetic variation.

Equilibrium models of isolation by distance predict an increase in genetic differentiation with geographic distance. Here we find a linear relationship between genetic and geographic distance in a worldwide sample of human populations, with major deviations from the fitted line explicable by admixture or extreme isolation. A close relationship is shown to exist between the correlation of geographic distance and genetic differentiation (as measured by F ST) and the geographic pattern of heterozygosity across populations. Considering a worldwide set of geographic locations as possible sources of the human expansion, we find that heterozygosities in the globally distributed populations of the data set are best explained by an expansion originating in Africa and that no geographic origin outside of Africa accounts as well for the observed patterns of genetic diversity. Although the relationship between F ST and geographic distance has been interpreted in the past as the result of an equilibrium model of drift and dispersal, simulation shows that the geographic pattern of heterozygosities in this data set is consistent with a model of a serial founder effect starting at a single origin. Given this serial-founder scenario, the relationship between genetic and geographic distance allows us to derive bounds for the effects of drift and natural selection on human genetic variation.genetic distance ͉ genetic drift ͉ HGDP-CEPH ͉ human origins ͉ microsatellites A regular decrease of genetic similarity with increasing geographic distance has been predicted by the theory of isolation by distance (1) and by the stepping-stone model (2), under the assumption that movement connected with mating is usually restricted to short distances (3, 4). Data on genetic polymorphisms have confirmed a strong association between genetic and geographic distance; early studies were generally limited to short geographic ranges and within-regional analyses (5, 6), but later studies have been extended to wider areas (7-9). Here, we regress a measure of genetic differentiation on geographic distance at the global level using 783 microsatellite loci from the Human Genome Diversity Project-Centre d'Etude du Polymorphisme Humain (HGDP-CEPH) worldwide sample of populations (10, 11). We then use simulations to examine a serial founder effect scenario as a possible explanation for the observed relationship between genetic and geographic distance. Materials and MethodsData.