Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution

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Abstract

We describe a model of neutral DNA evolution that allows substitution rates at a site to depend on the two flanking nucleotides ("context"), the branch of the phylogenetic tree, and position within the sequence and implement it by using a flexible and computationally efficient Bayesian Markov chain Monte Carlo approach. We then apply this approach to characterize phylogenetic variation in context-dependent substitution patterns in a 1.7-megabase genomic region in 19 mammalian species. In contrast to other substitution types, CpG transition substitutions have accumulated in a relatively clock-like fashion. More broadly, our results support the notion that context-dependent DNA replication errors, cytosine deamination, and biased gene conversion are major sources of naturally occurring mutations whose relative contributions have varied in mammalian evolution as a result of changes in generation times, effective population sizes, and recombination rates.

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Hwang, D. G., & Green, P. (2004). Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution. Proceedings of the National Academy of Sciences of the United States of America, 101(39), 13994–14001. https://doi.org/10.1073/pnas.0404142101

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