Purifying selection and the mtDNA clock (Soares et al. 2009)

This paper deals with the problem of a time-varying mutation rate due to purifying selection, i.e., the removal of harmful variation from the mtDNA gene pool.

From the paper:

Thus, it estimates the coalescence time of the mtDNA tree overall at ~160,000 kya, L3 (the clade that evolved within Africa and gave rise to the three major non-African haplogroups—sometimes termed ‘‘macrohaplogroups’’— M, N, and R) at 65 kya, and M, N, and R themselves at 40–50 kya.

...

In any event, L3 probably expanded ~70 kya, possibly associated with an improvement of the climatic conditions around that time after a long period of drought.103 There are no ‘‘pre-M’’ or ‘‘pre-N’’ clades extant either within or outside Africa, so the out-of-Africa event could be as early as the coalescence time of L3. These data render an outof- Africa dispersal prior to the Toba eruption in Sumatra at ~74 kya less likely.

...

the age of haplogroup M in India, at 49.4 (39.0; 60.2) kya, is significantly lower than in East Asia, at 60.6 (47.3; 74.3) kya (both are lower in r but the proportional
difference is similar; see Table 3).

...

Europe was first settled by modern humans ~45 kya, and it is believed that one of the branches of U, U5 or a genetically close ancestor to U5, arose among the first settlers. The ML estimate of haplogroup U5 is 36.0 (25.3; 47.2) kya, and lower with r at 30.7 (21.4; 40.5) kya and 33.0 (13.3; 52.8) with our synonymous rate. [...] The closest link in the tree with the Near East is the root of haplogroup U, placing any early migration into Europe involving U5 or its ancestors between ~55 kya and ~30 kya.

The new chronology of human mtDNA. As you can see, about 2/3 of the age of mtDNA represents within-Africa variation. L3 Africans and Eurasians are much closer related (matrilineally) than they are with any other Africans. The next closest relation is with L2 Africans, separated by L3's by ~43ky.



American Journal of Human Genetics doi:10.1016/j.ajhg.2009.05.001

Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock

Pedro Soares et al.

Abstract

There is currently no calibration available for the whole human mtDNA genome, incorporating both coding and control regions. Furthermore, as several authors have pointed out recently, linear molecular clocks that incorporate selectable characters are in any case problematic. We here confirm a modest effect of purifying selection on the mtDNA coding region and propose an improved molecular clock for dating human mtDNA, based on a worldwide phylogeny of > 2000 complete mtDNA genomes and calibrating against recent evidence for the divergence time of humans and chimpanzees. We focus on a time-dependent mutation rate based on the entire mtDNA genome and supported by a neutral clock based on synonymous mutations alone. We show that the corrected rate is further corroborated by archaeological dating for the settlement of the Canary Islands and Remote Oceania and also, given certain phylogeographic assumptions, by the timing of the first modern human settlement of Europe and resettlement after the Last Glacial Maximum. The corrected rate yields an age of modern human expansion in the Americas at 15 kya that - unlike the uncorrected clock - matches the archaeological evidence, but continues to indicate an out-of-Africa dispersal at around 5570 kya, 520 ky before any clear archaeological record, suggesting the need for archaeological research efforts focusing on this time window. We also present improved rates for the mtDNA control region, and the first comprehensive estimates of positional mutation rates for human mtDNA, which are essential for defining mutation models in phylogenetic analyses.

Link