АвторТема: Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Cl  (Прочитано 1592 раз)

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Correcting for Purifying Selection: An Improved Human Mitochondrial Molecular Clock


Pedro Soares1,Luca Ermini1,2,Noel Thomson3,Maru Mormina1,4,Teresa Rito5,Arne R?hl6,Antonio Salas7,Stephen Oppenheimer8,Vincent Macaulay3andMartin B. Richards1,Go To Corresponding Author,

1 Institute of Integrative and Comparative Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK
2 Laboratorio di Archeo-Antropologia molecolare/DNA antico, Universit? di Camerino, Camerino 62032, Italy
3 Department of Statistics, University of Glasgow, Glasgow G12 8QQ, UK
4 Leverhulme Centre for Human Evolutionary Studies, University of Cambridge, Cambridge CB2 1QH, UK
5 Liverpool School of Tropical Medicine, University of Liverpool, Liverpool L3 5QA, UK
6 Fluxus Technology, Clare, Suffolk CO10 8NN, UK
7 Unidade de Xen?tica, Instituto de Medicina Legal, and Departamento de Anatom?a Patol?gica y Ciencias Forenses, Facultad de Medicina de la Universidad de Santiago de Compostela, A Coru?a, Santiago de Compostela 15782, Galicia, Spain
8 School of Anthropology, University of Oxford, Oxford OX2 6PN, UK


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 thatunlike the uncorrected clockmatches 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.

http://www.cell.com/AJHG/abstract/S0002-9297(09)00163-3

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Received 11 February 2009;
revised 20 April 2009;
accepted 1 May 2009.
Published online: June 4, 2009.
Available online 4 June 2009.

 

© 2007 Молекулярная Генеалогия (МолГен)

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