1. The Influence of Rate Heterogeneity among Sites on the Time Dependence of Molecular Rates
- Author
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Alan Cooper, Julien Soubrier, Michael S. Y. Lee, Stéphane Guindon, Clio Der Sarkissian, Simon Y. W. Ho, Mike Steel, Australian Centre for Ancient DNA, University of Adelaide, Biomathematics Research Centre, University of Canterbury [Christchurch], Institut des Sciences Analytiques (ISA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), South Australian Museum, Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), School of Biological Sciences [Sydney], and The University of Sydney
- Subjects
0106 biological sciences ,Time Factors ,Bayesian probability ,Biology ,010603 evolutionary biology ,01 natural sciences ,Evolution, Molecular ,Correlation ,03 medical and health sciences ,Statistics ,Genetics ,Gamma distribution ,Among-site rate variation ,Computer Simulation ,Data partitioning ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Molecular clock ,Molecular Biology ,Ecology, Evolution, Behavior and Systematics ,030304 developmental biology ,0303 health sciences ,Base Sequence ,Models, Genetic ,Saturation (genetic) ,Nonparametric statistics ,Genetic Variation ,molecular clock ,time-dependent rates ,Mixture model ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,substitution rate ,Mutation ,divergence times ,[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM] - Abstract
International audience; Molecular evolutionary rate estimates have been shown to depend on the time period over which they are estimated. Factors such as demographic processes, calibration errors, purifying selection, and the heterogeneity of substitution rates among sites (RHAS) are known to affect the accuracy with which rates of evolution are estimated. We use mathematical modeling and Bayesian analyses of simulated sequence alignments to explore how mutational hotspots can lead to time-dependent rate estimates. Mathematical modeling shows that underestimation of molecular rates over increasing time scales is inevitable when RHAS is ignored. Although a gamma distribution is commonly used to model RHAS, we show that when the actual RHAS deviates from a gamma-like distribution, rates can either be under- or overestimated in a time-dependent manner. Simulations performed under different scenarios of RHAS confirm the mathematical modeling and demonstrate the impacts of time-dependent rates on estimates of divergence times. Most notably, erroneous rate estimates can have narrow credibility intervals, leading to false confidence in biased estimates of rates, and node ages. Surprisingly, large errors in estimates of overall molecular rate do not necessarily generate large errors in divergence time estimates. Finally, we illustrate the correlation between time-dependent rate patterns and differential saturation between quickly and slowly evolving sites. Our results suggest that data partitioning or simple nonparametric mixture models of RHAS significantly improve the accuracy with which node ages and substitution rates can be estimated.
- Published
- 2012