Selection Selection on mitochondrial DNA and the Neanderthal problem

Abstract

At present, the direct evidence for Neanderthal genetic variation and gene phylogeny is limited to the control region of the mitochondrial DNA (mtDNA). Neanderthal mtDNA sequences are divergent from those of recent humans. This fact, when coupled with the assumptions of selective neutrality and a recently expanding human population, argues for the complete and utter extinction of Neanderthals without living issue. But an alternative hypothesis is that human mtDNA has recently undergone an episode of positive selection, or a “selective sweep.” Five converging lines of evidence suggest that mtDNA has undergone recent positive selection: (1) mtDNA variants in living humans are associated with life history and metabolic traits that changed dramatically during recent human evolution; (2) Statistical tests show that the distribution of human mtDNA variation is clearly inconsistent with neutrality; (3) Nuclear genomic variation is not consistent with a single recent population expansion as necessary to explain human mtDNA variation; (4) A neutral mtDNA necessitates a population replacement to explain its pattern of variation, but many autosomal and X chromosomal loci show strong phylogeographic or genealogical evidence for the survival of archaic human gene lineages and therefore reject population replacement; and (5) Anatomical and archaeological evidence shows some degree of anatomical and behavioral continuity between Upper Paleolithic Neanderthals and later Europeans and likewise reject population replacement. The hypothesis of positive selection on mtDNA is in accord with recent estimates of genome-wide rates of selection and is contradicted by no known evidence. Molecular and comparative evidence further suggests that the current pattern of human mtDNA variation represents only the most recent episode of positive selection among many during human evolution. Selection on mtDNA cannot prove that other Neanderthal genomic lineages survived, although such survival may be suggested by other anatomical and genetic evidence. Nevertheless, the substantial probability of such selection renders Neanderthal mtDNA variation phylogenetically uninformative.