title: Improved calibration of the human mitochondrial clock using ancient genomes.
abstract: Reliable estimates of the rate at which DNA accumulates mutations (the substitution rate) are crucial for our understanding of the evolution and past demography of virtually any species. In humans, there are considerable uncertainties around these rates, with substantial variation among recent published estimates. Substitution rates have traditionally been estimated by associating dated events to the root (e.g., the divergence between humans and chimpanzees) or to internal nodes in a phylogenetic tree (e.g., first entry into the Americas). The recent availability of ancient mitochondrial DNA sequences allows for a more direct calibration by assigning the age of the sequenced samples to the tips within the human phylogenetic tree. But studies also vary greatly in the methodology employed and in the sequence panels analyzed, making it difficult to tease apart the causes for the differences between previous estimates. To clarify this issue, we compiled a comprehensive data set of 350 ancient and modern human complete mitochondrial DNA genomes, among which 146 were generated for the purpose of this study and estimated substitution rates using calibrations based both on dated nodes and tips. Our results demonstrate that, for the same data set, estimates based on individual dated tips are far more consistent with each other than those based on nodes and should thus be considered as more reliable.
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom a.rieux@ucl.ac.uk f.balloux@ucl.ac.uk.
authors.forename: Adrien
authors.initials: A
authors.lastname: Rieux
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Anders
authors.initials: A
authors.lastname: Eriksson
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Mingkun
authors.initials: M
authors.lastname: Li
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sobkowiak
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Lucy A
authors.initials: LA
authors.lastname: Weinert
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Vera
authors.initials: V
authors.lastname: Warmuth
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom.
authors.forename: Andres
authors.initials: A
authors.lastname: Ruiz-Linares
authors.affiliation: Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Andrea
authors.initials: A
authors.lastname: Manica
authors.affiliation: UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, United Kingdom a.rieux@ucl.ac.uk f.balloux@ucl.ac.uk.
authors.forename: François
authors.initials: F
authors.lastname: Balloux
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D001499:Bayes Theorem; D002138:Calibration; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D015894:Genome, Human; D054629:Genome, Mitochondrial; D006801:Humans; D059645:Mutation Rate; D010802:Phylogeny
keywords: Bayesian phylogenetic inference; ancient genomes; calibration strategy; divergence times; human; mitochondrial substitution rates; molecular clock
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