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Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock

BACKGROUND: The molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confound...

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Autor principal: Cabrera, Vicente M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325269/
https://www.ncbi.nlm.nih.gov/pubmed/32600249
http://dx.doi.org/10.1186/s12862-020-01640-5
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author Cabrera, Vicente M.
author_facet Cabrera, Vicente M.
author_sort Cabrera, Vicente M.
collection PubMed
description BACKGROUND: The molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study, I propose a new algorithm for estimating the coalescent age of phylogenetically related sequences, taking into account the observed time-dependent effect on the molecular rate detected by others. RESULTS: By applying this method to real human mitochondrial DNA trees with shallow and deep topologies, I obtained significantly older molecular ages for the main events of human evolution than were previously estimated. These ages are in close agreement with the most recent archaeological and paleontological records favoring the emergence of early anatomically modern humans in Africa 315 ± 34 thousand years ago (kya) and the presence of recent modern humans outside of Africa as early as 174 ± 48 thousand years ago. Furthermore, during the implementation process, I demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size, which is in better accordance with the fact that under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift. CONCLUSIONS: I suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time-dependent effect observed for the substitution rate, and I propose a new method that corrects for this effect.
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spelling pubmed-73252692020-06-30 Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock Cabrera, Vicente M. BMC Evol Biol Methodology Article BACKGROUND: The molecular clock is an important genetic tool for estimating evolutionary timescales. However, the detection of a time-dependent effect on substitution rate estimates complicates its application. It has been suggested that demographic processes could be the main cause of this confounding effect. In the present study, I propose a new algorithm for estimating the coalescent age of phylogenetically related sequences, taking into account the observed time-dependent effect on the molecular rate detected by others. RESULTS: By applying this method to real human mitochondrial DNA trees with shallow and deep topologies, I obtained significantly older molecular ages for the main events of human evolution than were previously estimated. These ages are in close agreement with the most recent archaeological and paleontological records favoring the emergence of early anatomically modern humans in Africa 315 ± 34 thousand years ago (kya) and the presence of recent modern humans outside of Africa as early as 174 ± 48 thousand years ago. Furthermore, during the implementation process, I demonstrated that in a population with fluctuating sizes, the probability of fixation of a new neutral mutant depends on the effective population size, which is in better accordance with the fact that under the neutral theory of molecular evolution, the fate of a molecular mutation is mainly determined by random drift. CONCLUSIONS: I suggest that the demographic history of populations has a more decisive effect than purifying selection and/or mutational saturation on the time-dependent effect observed for the substitution rate, and I propose a new method that corrects for this effect. BioMed Central 2020-06-29 /pmc/articles/PMC7325269/ /pubmed/32600249 http://dx.doi.org/10.1186/s12862-020-01640-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Methodology Article
Cabrera, Vicente M.
Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
title Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
title_full Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
title_fullStr Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
title_full_unstemmed Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
title_short Counterbalancing the time-dependent effect on the human mitochondrial DNA molecular clock
title_sort counterbalancing the time-dependent effect on the human mitochondrial dna molecular clock
topic Methodology Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325269/
https://www.ncbi.nlm.nih.gov/pubmed/32600249
http://dx.doi.org/10.1186/s12862-020-01640-5
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