Selection in human mtDNA

The issue of selection on human mtDNA is quite controversial, because mtDNA has been used to infer patterns of human history and prehistory. In particular, the identification of the coalescence of human mitochondria types to a recent "African Eve" ancestor has been one of the arguments in favor of the recent Out of Africa replacement hypothesis.

A new study in Genetics examines the role that selection has played in the evolution of human mtDNA.

The coalescent date of the human mitochondrial DNA tree using this rate is 160,000 (S.D. 22,000) years. This coalescent date is broadly consistent with the dates of the Homo sapiens fossils recognized so far from Ethiopia (CLARK et al. 2003; MCDOUGALL et al. 2005; WHITE et al. 2003). The most recent common ancestor of all the Eurasian, American, Australian, Papua New Guinean and African lineages in clade L3 dates to 65,000 ± 8,000 years while the average coalescent time of the three basic non-African founding haplogroups M, N, and R is 45,000 years.

This confirms my previous observation that mtDNA variation in humans points to increased diversity among African populations who are descended partially from ancient "Paleoafrican" populations, while Africans and non-Africans are descended from "Afrasians", a group probably living in Africa in the last few tens of thousands of years and containing a subset of the diversity of the widely dispersed anatomically modern population of Africa. The date of the "Afrasian" group L3 is roughly compatible with the ~40kBP date for the wide appearance of modern humans in Eurasia and the emergence of modern behavior. The coalescence times of Eurasian mtDNA are also comparable with that of the Microcephalin variants, which (like M, N, and R) also show a primary non-African distribution.

Getting back to the paper:

The direction of threonine and valine substitution with other amino acids was significantly different between populations with neutral and significantly negative Tajima’s D values, respectively (Table 3), and between haplogroups: in H1 sequences sampled broadly from Europe and Near East, 7 of 11 non-synonymous mutations resulted in the replacement of threonine and valine with alanine and isoleucine, while only three mutations resulted in a change towards threonine or valine (Figure 1). In contrast to this pattern, in haplogroup V sequences from Finland (FINNILÄ et al. 2001), where populations continued to rely largely on hunting and fishing for subsistence even after the first contacts with farmers, 6 of 7 replacement polymorphisms resulted in a change to threonine and valine, and none in the replacement of the latter two amino acids (p<0.01). style="font-weight: bold;">The potential role of selection in affecting fixation probabilities at different non-silent positions undermines the appropriateness of using the average mitochondrial clock over all sites in dating events in human population history. Despite the evidence of departures from neutrality and high levels of homoplasy at the interspecies level, the phylogenetic approach for analyzing mtDNA sequence data at the intraspecies level remains viable because the reconstruction of the basic branches is robust and the excess of non-synonymous substitutions affects mainly the terminal branches of the tree.

What the authors are basically saying is that the basic branches of the tree don't show a substantial evidence of selection. This is not surprising, since these are old lineages that have withstood the test of time. It is the younger "unproven" terminal branches, i.e., the more recent lineages within the major branches that show evidence of selection.

One has to wonder whether the basic branches may also have been the remnant of selection from a wider pool of mtDNA variants. That is, they may be the variants that have survived in competition with their cousins when they too were young, tens of thousands of years ago.

Genetics (online early)

The role of selection in the evolution of human mitochondrial genomes

Toomas Kivisild et al.

Abstract

High mutation rate in mammalian mitochondrial DNA generates a highly divergent pool of alleles even within species that have dispersed and expanded in size recently. Phylogenetic analysis of 277 human mitochondrial genomes revealed a significant (p<0.01) excess of rRNA and non-synonymous base substitutions among hotspots of recurrent mutation. Most hotspots involved transitions from guanine to adenine that, together with thymine to cytosine transitions, illustrate the asymmetric bias in codon usage at synonymous sites on the heavy-strand DNA. The mitochondrion-encoded tRNAThr varied significantly more than any other tRNA gene. Threonine and valine codons were involved in 259 of the 414 amino acid replacements observed. The ratio of non-synonymous changes from and to threonine and valine differed significantly (P=0.003) between populations with neutral (22/58) and those with significantly negative Tajima's D values (70/76), independent of their geographic location. In contrast to a recent suggestion that the excess of non-silent mutations is characteristic to Arctic populations implying their role in cold adaptation, we demonstrate that the surplus of non-synonymous mutations is a general feature of the young branches of the phylogenetic tree, affecting also those that are found only in Africa. We introduce a new calibration method of the mutation rate of synonymous transitions to estimate the coalescent times of mtDNA haplogroups.

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