A human population bottleneck can account for the discordance between patterns of mitochondrial versus nuclear DNA variation.

Abstract

Whether or not humans have experienced a reduction in population size in the recent past is a controversial issue germane to the origin and colonization of our own species (Stringer and Andrews 1988). A change in population size can result in deviations from the neutral patterns of nucleotide variation expected at equilibrium. Using the frequency distribution of mutations segregating in extant populations, the magnitude of a deviation can be measured by Tajima’s (1989a) D statistic or by a number of alternative measures (Fu and Li 1993; Fu 1996). In a population of constant size, variation at a neutrally evolving locus is expected to have a D value of approximately zero. Following a reduction in population size, rare frequency mutations are lost more readily than are common mutations (Nei, Maruyama, and Chakraborty 1975), and transient positive D values are expected (Tajima 1989b). Following an increase in population size, there is a temporary excess of new mutations segregating at rare frequencies, and negative D values are expected. The sign of Tajima’s D subsequent to a population bottleneck can be positive, negative, or zero depending on the length of time since the bottleneck and the severity of the bottleneck. If a bottleneck is so severe that all variation is eliminated or lasts so long that the population reaches a new equilibrium, Tajima’s D follows the pattern produced by an expansion in population size. However, following an incomplete bottleneck, Tajima’s D is transiently positive before becoming negative and eventually approaching its equilibrium (Tajima 1989b). In humans, mitochondrial variation is characterized by an excess of rare frequency mutations and a negative D value, which has been interpreted as the result of a recent expansion in population size (Merriwether et al. 1991; Rogers and Harpending 1992). In contrast, most nuclear loci are characterized by the opposite pattern, an excess of common mutations and positive D values, which can result from a recent reduction in population size (Hey 1997; Harding et al. 1997; Clark et al. 1998; Zietkiewicz et al. 1998). The conflicting profiles of mitochondrial and nuclear variation have led to the suggestion that these patterns cannot be simultaneously accounted for by human population history, which must be shared by both genomes (Hey 1997).