Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock

Soares, P., Ermini, L., Thomson, N., Mormina, M., Rito, T., Rohl, A., Salas, A., Oppenheimer, S., Macaulay, V. and Richards, M. B. (2009) Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock. American Journal of Human Genetics, 84(6), pp. 740-759. (doi: 10.1016/j.ajhg.2009.05.001)

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 similar to 15 kya that-unlike the uncorrected clock matches the archaeological evidence, but continues to indicate an out-of-Africa dispersal at around 55-70 kya, 5-20 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.

• Item Type: Articles
• Keywords: Canary Islands Coding region DIVERGENCE TIMES DNA DNA-SEQUENCES Europe GENOME VARIATION MACROHAPLOGROUP-M MAXIMUM-LIKELIHOOD MODEL MODELS MtDNA MTDNA VARIATION MUTATIONS PHYLOGENETIC NETWORK RECORD RESEARCH RIBOSOMAL-RNA GENES SELECTION SOUTHWEST PACIFIC TIME DEPENDENCY Trend
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macaulay, Dr Vincent
• Authors: Soares, P., Ermini, L., Thomson, N., Mormina, M., Rito, T., Rohl, A., Salas, A., Oppenheimer, S., Macaulay, V., and Richards, M. B.
• College/School: College of Science and Engineering > School of Mathematics and Statistics > Statistics
• Journal Name: American Journal of Human Genetics
• ISSN: 0002-9297