Estimating mutation rate and generation time from longitudinal samples of DNA sequences.
We present in this paper a simple method for estimating the mutation rate per site per year which also yields an estimate of the length of a generation when mutation rate per site per generation is known. The estimator, which takes advantage of DNA polymorphisms in longitudinal samples, is unbiased under a number of population models, including population structure and variable population size over time. We apply the new method to a longitudinal sample of DNA sequences of the env gene of human immunodeficiency virus type 1 (HIV-1) from a single patient and obtain 1.62 x 10(-2) as the mutation rate per site per year for HIV-1. Using an independent data set to estimate the mutation rate per generation, we obtain 1.8 days as the length of a generation of HIV-1, which agrees well with recent estimates based on viral load data. Our estimate of generation time differs considerably from a recent estimate by Rodrigo et al. when the same mutation rate per site per generation is used. Some factors that may contribute to the difference among different estimators are discussed.
Human Genetics Center, University of Texas at Houston, 77030, USA. fu@hgc.sph.uth.tmc.edu
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D000818:Animals; D001483:Base Sequence; D004252:DNA Mutational Analysis; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009154:Mutation / Q000235:genetics*; D013995:Time