A Human Population Bottleneck Can Account For The Discordance Between Patterns Of Mitochondrial Versus Nuclear Dna Variation

Letter to the Editor
A Human Population Bottleneck Can Account for the Discordance Between Patterns of
Mitochondrial Versus Nuclear DNA Variation
Justin C. Fay* and Chung-I Wu*†
*Committee on Genetics and †Department of Ecology and Evolution, University of Chicago

Whether or not humans have experienced a reduction in population size in the recent past is a controversial issue germane tothe 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 alternativemeasures (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 increasein 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 solong 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 anegative
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).
Abbreviation: mtDNA, mitochondrial DNA.
Key words: population bottleneck, human evolution, Homo sapiens.
Address for correspondence and reprints:Justin Fay, Committee
on Genetics, 1101 East 57th Street, Chicago, Illinois 60637. E- mail:
jfay@midway.uchicago.edu.
Mol. Biol. Evol. 16(7):1003–1005. 1999
1999 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038

Since the mitochondrial genome has an effective
population size one quarter that of an average nuclear
locus, its patterns of variation may be quite differentfollowing a change in population size. While current
explanations must invoke complex demographic histories or selection, we have found using computer simulations that the apparently incongruent patterns of mitochondrial and nuclear variation are in fact quite compatible with a recent human population bottleneck.
Patterns and levels of nucleotide variation are commonly summarized by ˆ and ˆ , twoestimators of the
population parameter , equal to four times the product
of the effective population size and the mutation rate.
In a sample of n genes, ˆ is the average number of
pairwise differences, and ˆ
S/an, where S is the number of segregating sites and an is the sum of 1 1/2
1/3
...
1/(n
1) (Watterson 1975). Tajima’s D
measures the difference between ˆ and ˆ divided by the...