Ancestral alleles and population origins: inferences depend on mutation rate

Previous studies have found that at most human loci, ancestral alleles are "African," in the sense that they reach their highest frequency there. Conventional wisdom holds that this reflects a recent African origin of modern humans. This paper challenges that view by showing that the empirical pattern (of elevated allele frequencies within Africa) is not as pervasive as has been thought. We confirm this African bias in a set of mainly protein-coding loci, but find a smaller bias in Alu insertion polymorphisms, and an even smaller bias in noncoding loci. Thus, the strong bias that was originally observed must reflect some factor that varies among data sets--something other than population history. This factor may be the per-locus mutation rate: the African bias is most pronounced in loci where this rate is high. The distribution of ancestral alleles among populations has been studied using 2 methods. One of these involves comparing the fractions of loci that reach maximal frequency in each population. The other compares the average frequencies of ancestral alleles. The first of these methods reflects history in a manner that depends on the mutation rate. When that rate is high, ancestral alleles at most loci reach their highest frequency in the ancestral population. When that rate is low, the reverse is true. The other method--comparing averages--is unresponsive. Average ancestral allele frequencies are affected neither by mutation rate nor by the history of population size and migration. In the absence of selection and ascertainment bias, they should be the same everywhere. This is true of one data set, but not of 2 others. This also suggests the action of some factor, such as selection or ascertainment bias, that varies among data sets.