scholarly journals Counterbalancing the time-dependence effect on the Human Mitochondrial DNA Molecular Clock

2019 ◽  
Author(s):  
vicente M Cabrera
Keyword(s):  
Mitochondrial Dna ◽  
Time Dependence ◽  
Molecular Clock ◽  
Demographic History ◽  
Neutral Theory ◽  
Purifying Selection ◽  
Time Dependency ◽  
Effective Population ◽  
Modern Humans ◽  
Human Mitochondrial Dna

Abstract Background The molecular clock is the most important genetic tool to estimate evolutionary timescales. However, the detection of a time dependency effect on the mutation rate estimates is complicating 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 to estimate the coalescent age of phylogenetically related sequences, taking into account the observed time dependency effect on the molecular rate detected by others.Results Applying this method to real human mitochondrial DNA trees, with shallow and deep topologies, I have obtained significantly older molecular ages for the main events of human evolution than in previous estimates. These ages are in close agreement with the most recent archaeological and paleontological records that are in favor of an emergence of early anatomically modern humans in Africa at 315 ± 34 thousand years ago and the presence of recent modern humans out of Africa as early as 174 ± 48 thousand years ago. Furthermore, in the implementation process, we 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 more in 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 dependence effect observed for the substitution rate.

scholarly journals Counterbalancing the time-dependence effect on the Human Mitochondrial DNA Molecular Clock

2020 ◽  
Author(s):  
Vicente M Cabrera
Keyword(s):  
Mitochondrial Dna ◽  
Time Dependence ◽  
Molecular Clock ◽  
Substitution Rate ◽  
Demographic History ◽  
Time Dependency ◽  
Effective Population ◽  
Modern Humans ◽  
Random Drift ◽  
Human Mitochondrial Dna

Abstract Background: The molecular clock is an important genetic tool to estimate evolutionary timescales. However, the detection of a time dependency effect on the substitution rate estimates is complicating 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 to estimate the coalescent age of phylogenetically related sequences, taking into account the observed time dependency effect on the molecular rate detected by others. Results: Applying this method to real human mitochondrial DNA trees, with shallow and deep topologies, I have obtained significantly older molecular ages for the main events of human evolution than in previous estimates. These ages are in close agreement with the most recent archaeological and paleontological records that are in favor of an emergence of early anatomically modern humans in Africa at 315 ± 34 thousand years ago and the presence of recent modern humans out of Africa as early as 174 ± 48 thousand years ago. Furthermore, in the implementation process, we 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 more in 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 dependence effect observed for the substitution rate and propose a new method that corrects for this effect.

scholarly journals Counterbalancing the time-dependence effect on the Human Mitochondrial DNA Molecular Clock

2020 ◽  
Author(s):  
vicente M Cabrera
Keyword(s):  
Mitochondrial Dna ◽  
Molecular Clock ◽  
Substitution Rate ◽  
Demographic History ◽  
Time Dependent ◽  
Effective Population ◽  
Modern Humans ◽  
Human Mitochondrial Dna ◽  
Dependent Effect ◽  
Time Dependent Effect

Abstract 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.

scholarly journals Counterbalancing the time-dependence effect on the human mitochondrial DNA molecular clock

2018 ◽  
Author(s):  
Vicente M. Cabrera
Keyword(s):  
Mitochondrial Dna ◽  
Time Dependence ◽  
Human Evolution ◽  
Molecular Clock ◽  
Close Agreement ◽  
New Method ◽  
Time Dependency ◽  
Human Mitochondrial Dna

AbstractWe propose a new method for estimating the coalescent age of phylogenetically related sequences that takes into account the observed time dependency of molecular rate estimates. Applying this method to human mitochondrial DNA data we have obtained significantly older ages for the main events of human evolution than in previous estimates. These ages are in close agreement with the most recent archaeological and paleontological records.

scholarly journals Characterizing the Time Dependency of Human Mitochondrial DNA Mutation Rate Estimates

2008 ◽  
Vol 26 (1) ◽  
pp. 217-230 ◽  
Author(s):  
B. M. Henn ◽  
C. R. Gignoux ◽  
M. W. Feldman ◽  
J. L. Mountain
Keyword(s):  
Mitochondrial Dna ◽  
Mutation Rate ◽  
Time Dependency ◽  
Mitochondrial Dna Mutation ◽  
Human Mitochondrial Dna ◽  
Dna Mutation

scholarly journals Evaluating the Impact of Purifying Selection on Species-level Molecular Dating

2019 ◽  
Author(s):  
Chong He ◽  
Dan Liang ◽  
Peng Zhang
Keyword(s):  
Molecular Clock ◽  
Neutral Theory ◽  
Purifying Selection ◽  
Selective Constraint ◽  
Species Level ◽  
Molecular Dating ◽  
Substitution Saturation ◽  
Time Estimates ◽  
Branch Lengths ◽  
The Impact

AbstractThe neutral theory of molecular evolution suggests that the constancy of the molecular clock relies on the neutral condition. Thus, purifying selection, the most common type of natural selection, could influence the constancy of the molecular clock, and the use of genes/sites under purifying selection may produce less reliable molecular dating results. However, in current practices of species-level molecular dating, some researchers prefer to select slowly evolving genes/sites to avoid the potential impact of substitution saturation. These genes/sites are generally under a strong influence of purifying selection. Here, from the data of 23 published mammal genomes, we constructed datasets under various selective constraints. We compared the differences in branch lengths and time estimates among these datasets to investigate the impact of purifying selection on species-level molecular dating. We found that as the selective constraint increases, terminal branches are extended, which introduces biases into the result of species-level molecular dating. This result suggests that in species-level molecular dating, the impact of purifying selection should be taken into consideration, and researchers should be more cautious with the use of genes/sites under purifying selection.

scholarly journals Carriers of human mitochondrial DNA macrohaplogroup M colonized India from southeastern Asia

2016 ◽  
Author(s):  
Patricia Marrero ◽  
Khaled K. Abu-Amero ◽  
Jose M Larruga ◽  
Vicente M Cabrera
Keyword(s):  
Mitochondrial Dna ◽  
Arabian Peninsula ◽  
Indian Subcontinent ◽  
Modern Humans ◽  
The West ◽  
West Side ◽  
Human Mitochondrial Dna ◽  
Phylogeographic Analysis ◽  
History Of ◽  
Out Of Africa

ABSTRACTObjetivesWe suggest that the phylogeny and phylogeography of mtDNA macrohaplogroup M in Eurasia and Australasia is better explained supposing an out of Africa of modern humans following a northern route across the Levant than the most prevalent southern coastal route across Arabia and India proposed by others.MethodsA total 206 Saudi samples belonging to macrohaplogroup M have been analyzed. In addition, 4107 published complete or nearly complete Eurasian and Australasian mtDNA genomes ascribed to the same macrohaplogroup have been included in a global phylogeographic analysis.ResultsMacrohaplogroup M has only historical implantation in West Eurasia including the Arabian Peninsula. Founder ages of M lineages in India are significantly younger than those in East Asia, Southeast Asia and Near Oceania. These results point to a colonization of the Indian subcontinent by modern humans carrying M lineages from the east instead the west side.ConclusionsThe existence of a northern route previously advanced by the phylogeography of mtDNA macrohaplogroup N is confirmed here by that of macrohaplogroup M. Taking this genetic evidence and those reported by other disciplines we have constructed a new and more conciliatory model to explain the history of modern humans out of Africa.

scholarly journals Human molecular evolutionary rate, time dependency and transient polymorphism effects viewed through ancient and modern mitochondrial DNA genomes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Vicente M. Cabrera
Keyword(s):  
Mutation Rate ◽  
Molecular Clock ◽  
Substitution Rate ◽  
Evolutionary Rate ◽  
Evolutionary Genetics ◽  
Modern Human ◽  
Human Populations ◽  
Time Dependency ◽  
Effective Population ◽  
Complete Mitochondrial Genomes

AbstractHuman evolutionary genetics gives a chronological framework to interpret the human history. It is based on the molecular clock hypothesis that suppose a straightforward relationship between the mutation rate and the substitution rate with independence of other factors as demography dynamics. Analyzing ancient and modern human complete mitochondrial genomes we show here that, along the time, the substitution rate can be significantly slower or faster than the average germline mutation rate confirming a time dependence effect mainly attributable to changes in the effective population size of the human populations, with an exponential growth in recent times. We also detect that transient polymorphisms play a slowdown role in the evolutionary rate deduced from haplogroup intraspecific trees. Finally, we propose the use of the most divergent lineages within haplogroups as a practical approach to correct these molecular clock mismatches.

scholarly journals The Rate of Molecular Evolution When Mutation May Not Be Weak

2018 ◽  
Author(s):  
A.P. Jason de Koning ◽  
Bianca D. De Sanctis
Keyword(s):  
Natural Selection ◽  
Molecular Evolution ◽  
Population Size ◽  
Mutation Rate ◽  
Molecular Clock ◽  
Neutral Theory ◽  
Neutral Evolution ◽  
Systematic Bias ◽  
Effective Population ◽  
Sequence Comparisons

AbstractOne of the most fundamental rules of molecular evolution is that the rate of neutral evolution equals the mutation rate and is independent of effective population size. This result lies at the heart of the Neutral Theory, and is the basis for numerous analytic approaches that are widely applied to infer the action of natural selection across the genome and through time, and for dating divergence events using the molecular clock. However, this result was derived under the assumption that evolution is strongly mutation-limited, and it has not been known whether it generalizes across the range of mutation pressures or the spectrum of mutation types observed in natural populations. Validated by both simulations and exact computational analyses, we present a direct and transparent theoretical analysis of the Wright-Fisher model of population genetics, which shows that some of the most important rules of molecular evolution are fundamentally changed by considering recurrent mutation’s full effect. Surprisingly, the rate of the neutral molecular clock is found to have population-size dependence and to not equal the mutation rate in general. This is because, for increasing values of the population mutation rate parameter (θ), the time spent waiting for mutations quickly becomes smaller than the cumulative time mutants spend segregating before a substitution, resulting in a net deceleration compared to classical theory that depends on the population mutation rate. Furthermore, selection exacerbates this effect such that more adaptive alleles experience a greater deceleration than less adaptive alleles, introducing systematic bias in a wide variety of methods for inferring the strength and direction of natural selection from across-species sequence comparisons. Critically, the classical weak mutation approximation performs well only when θ< 0.1, a threshold that many biological populations seem to exceed.

scholarly journals Evolution of the genetic architecture of local adaptations under genetic rescue is determined by mutational load and polygenicity

2020 ◽  
Author(s):  
Yulin Zhang ◽  
Aaron J. Stern ◽  
Rasmus Nielsen
Keyword(s):  
Complex Traits ◽  
Genetic Architecture ◽  
Demographic History ◽  
Purifying Selection ◽  
Mutational Load ◽  
Genetic Rescue ◽  
Effective Population ◽  
Lower Efficiency ◽  
Local Adaptations ◽  
Inbred Populations

AbstractInbred populations often suffer from heightened mutational load and decreased fitness due to lower efficiency of purifying selection at small effective population size. Genetic rescue (GR) is a tool that is studied and deployed with the aim of increasing fitness of such inbred populations. The success of GR is known to depend on certain factors that may vary between different populations, such as their demographic history and distribution of dominance effects of mutations. While we understand the effects of these factors on the evolution of overall ancestry in the inbred population after GR, it is less clear what the effect is on local adaptations and their genetic architecture. To this end, we conduct a population genetic simulation study evaluating the effect of several different factors on the efficacy of GR including trait complexity (Mendelian vs. polygenic), dominance effects, and demographic history. We find that the effect on local adaptations depends highly on the mutational load at the time of GR, which is shaped dynamically by interactions between demographic history and dominance effects of deleterious variation. While local adaptations are generally restored post-GR in the long run, in the short term they are often compromised in the process of purging deleterious variation. We also show that while local adaptations are almost always fully restored, the degree to which ancestral genetic variation comprising the trait is replaced by donor variation can vary drastically, and is especially high for complex traits. Our results provide considerations for practical GR and its effects on trait evolution.

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