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Abstract
The availability of evolutionary rate estimates in recent years led to the observation that they may depend on the time-scale on which they are measured. Specifically, RNA virus evolutionary rates are frequently estimated to be low towards the past and high towards the present. This time-dependent rate phenomenon (TDRP) has important implications for evolutionary studies as it could severely bias divergence time estimates. While recent studies are providing insights into the relationship between viral evolutionary rate and time, formal probabilistic models to draw inference under TDRP scenarios remain lacking. Here, we adopt epoch-modelling to develop a Bayesian model of discrete rate changes through time in an unknown evolutionary history and combine this with a log-linear parameterization of rates as a function of times in the past. We provide an implementation for nucleotide substitution rates as well as for nonsynonymous rates change in a codon substitution model. Using a foamy virus dataset for which internal node calibrations can be applied based on host-virus co-divergence, we estimate a significant decline in evolutionary rates as a function of time into the past for nucleotide substitutions as well as for non-synonymous substitutions in a codon model. We also estimate a deep evolutionary history for primate Lentiviruses by combining an HIV-1 group M node calibration and a biogeographic calibration for viruses in drill monkeys in the TDRP model. Our analyses lead to the conclusion that studies of evolutionary timescales require a reconsideration of substitution rates, in either codon and nucleotide substitution model, as a dynamic feature of molecular evolution.
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1 Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium
2 Departments of Biomathematics and Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095, USA; Department of Biostatistics, UCLA Fielding School of Public Health, University of California, Los Angeles, CA 90095, USA