Climate shaped the worldwide distribution of human mitochondrial DNA sequence variation

Abstract

There is an ongoing discussion in the literature on whether human mitochondrial DNA (mtDNA) evolves neutrally. There have been previous claims for natural selection on human mtDNA based on an excess of non-synonymous mutations and higher evolutionary persistence of specific mitochondrial mutations in Arctic populations. However, these findings were not supported by the reanalysis of larger datasets. Using a geographical framework, we perform the first direct test of the relative extent to which climate and past demography have shaped the current spatial distribution of mtDNA sequences worldwide. We show that populations living in colder environments have lower mitochondrial diversity and that the genetic differentiation between pairs of populations correlates with difference in temperature. These associations were unique to mtDNA; we could not find a similar pattern in any other genetic marker. We were able to identify two correlated non-synonymous point mutations in the ND3 and ATP6 genes characterized by a clear association with temperature, which appear to be plausible targets of natural selection producing the association with climate. The same mutations have been previously shown to be associated with variation in mitochondrial pH and calcium dynamics. Our results indicate that natural selection mediated by climate has contributed to shape the current distribution of mtDNA sequences in humans.

Figure 1.

Map of locations of populations from which HVS-I sequences (black) and complete mtDNA genomes (yellow) were obtained. The background colour gradient (blue to red) represents the minimum temperature.

Figure 2.

Relationship between mtDNA within-population genetic diversity, distance from sub-Saharan Africa and minimum temperature: (a) genetic diversity for mitochondrial HVS-I sequences against distance from Africa (km); (b) genetic diversity for mitochondrial HVS-I sequences against minimum temperature, after correcting for distance from Africa; (c) genetic diversity for complete mitochondrial genome sequences against distance from Africa (km); and (d) genetic diversity for complete mitochondrial genome sequences against minimum temperature, after correcting for distance from Africa.

Figure 3.

Relationship between within-population genetic diversity, distance from sub-Saharan Africa and minimum temperature: genetic diversity against distance from Africa (km) at (a) autosomal microsatellites, (c) autosomal SNPs, (e) X-chromosome microsatellites and (g) Y-chromosome microsatellites; genetic diversity against minimum temperature, after correcting for distance from Africa, at (b) autosomal microsatellites, (d) autosomal SNPs, (f) X-chromosome microsatellites and (h) Y-chromosome microsatellites.

Figure 4.

Association between minimum temperature and allele frequency at two non-synonymous mitochondrial SNPs: (a) 8701 and (b) 10398. The frequency of the derived A nucleotide was plotted in both panels. The size of the points is proportional to the sample size of the various populations. African populations are represented in black, European in green, Asian in purple, American in blue and Oceanian in orange.

Figure 5.

Phylogenetic tree for the complete mitochondrial genome dataset. (a) Ancestral and derived states for the 8701G/A and 10398G/A SNPs. Blue, SNP 8701 = ‘G’, SNP 10398 = ‘G’; yellow, SNP 8701 = ‘A’, SNP 10398 = ‘A’; violet, SNP 8701 = ‘A’, SNP 10398 = ‘G’; red, SNP 8701 = ‘G’, SNP 10398 = ‘A’. (b) Bootstrap support values are indicated by pie charts with supported partitions displayed in green and unsupported ones in pink.