MBE Advance Access published online on January 30, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm018
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Research Article |
Ancestral Alleles and Population Origins: Inferences Depend on Mutation Rate
* Dept. of Anthropology, 270S 1400E RM 102, Univ. of Utah, Salt Lake City, UT 84112
Dept. of Human Genetics, Univ. of Utah School of Medicine, Salt Lake City, UT 84112
Dept. of Biological Sciences, Biological Computation and Visualization Center, Center for BioModular Multi-Scale Systems, Louisiana State Univ. , 202 Life Sciences Building, Baton Rouge, Louisiana 70803
Corresponding author: Alan R. Rogers, Dept. of Anthropology, 270S 1400E RM 102, Univ. of Utah, Salt Lake City, UT 84112. rogers{at}anthro.utah.edu. FAX: 801-581-6252
Accepted for publication January 19, 2007.
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, first 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 insertion polymorphisms, and an even smaller bias in non-coding 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 two 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 two others. This also suggests the action of some factor, such as selection or ascertainment bias, that varies between data sets.
Key Words: Ancestral allele • last common ancestor • human evolutionary history • replacement hypothesis • multiregional hypothesis • diffusion wave hypothesis