Comparative nuclear and mitochondrial genome diversity in humans and chimpanzees

Abstract

Restriction mapping and sequencing have shown that humans have substantially lower levels of mitochondrial genome diversity (d) than chimpanzees. In contrast, humans have substantially higher levels of heterozygosity (H) at protein-coding loci, suggesting a higher level of diversity in the nuclear genome. To investigate the discrepancy further, we sequenced a segment of the mitochondrial genome control region (CR) from 49 chimpanzees. The majority of these were from the Pan troglodytes versus subspecies, which was underrepresented in previous studies. We also estimated the average heterozygosity at 60 short tandem repeat (STR) loci in both species. For a total sample of 115 chimpanzees, d = 0.075 +/0 0.037, compared to 0.020 +/- 0.011 for a sample of 1,554 humans. The heterozygosity of human STR loci is significantly higher than that of chimpanzees. Thus, the higher level of nuclear genome diversity relative to mitochondrial genome diversity in humans is not restricted to protein-coding loci. It seems that humans, not chimpanzees, have an unusual d/H ratio, since the ratio in chimpanzees is similar to that in other catarrhines. This discrepancy in the relative levels of nuclear and mitochondrial genome diversity in the two species cannot be explained by differences in mutation rate. However, it may result from a combination of factors such as a difference in the extent of sex ratio disparity, the greater effect of population subdivision on mitochondrial than on nuclear genome diversity, a difference in the relative levels of male and female migration among subpopulations, diversifying selection acting to increase variation in the nuclear genome, and/or directional selection acting to reduce variation in the mitochondrial genome.

Cultural Selection and Genetic Diversity in Humans

“…Our common Y-chromosome, male, ancestor seems even more remarkably recent (Seielstad et al 1999;Shen et al 2000; Thomson et al 2000;Underhill et al 2000). Compared with other apes, we have, despite our large current population, relatively low effective mtDNA and Y-chromosome population sizes (Gagneux et al 1999;Stone et al 2002) and a low ratio of mtDNA diversity to nuclear heterozygosity (Wise et al 1997). Furthermore, different patterns of human evolution are suggested by different genetic markers or by the same marker in different regions (Harpending and Rogers 2001;Harris and Hey 1999).…”

Comparison of DNA and protein polymorphisms between humans and chimpanzees.

“…Therefore, like the silent nucleotide diversity, chimpanzees should have high heterozygosity at microsatellite loci. Table 3, however, shows that the average heterozygosity (H) at 80 microsatellite loci is similar in humans and chimpanzees (Couau-Roy et al 1996, Wise et al 1997. The average number of alleles per locus is also almost the same.…”

“…Since these sequence data are compilations from several independent studies (see refs. in Wise et al 1997), the number of segregating sites is not available. Abbreviations are the same as in Table 1. species is attributed to either sampling errors or differences in mutation rates among different loci.…”

“…On the other hand, the nucleotide diversity has scarcely been examined in non-human primates. Available chimpanzee DNA sequences are limited to mitochondrial (mt) DNA (Morrin et al 1994, Ruvolo et al 1994, Wise et al 1997, 1998), a 10kb non-coding region on the X chromosome (Kaessman et al 1999a) and an intergenic region adjacent to the HOXB6 gene locus on chromosome 17 (Deinard and Kidd 1999). The nucleotide diversity estimated for these regions is significantly higher in chimpanzees than in humans.…”

Order emerging from chaos in human evolutionary genetics

“…This was not, of course, the first time that anyone had suggested a role for natural selection in the evolution of human mitochondria (21)(22)(23)(24). The problem is that selection and population growth can be hard to tell apart.…”