Bayesian Markov chain Monte Carlo sequence analysis reveals varying neutral substitution patterns in mammalian evolution.
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.
Hwang
Dick G
DG
Department of Genome Sciences and Howard Hughes Medical Institute, University of Washington, Box 357730, Seattle, WA 98195, USA. dhwang@u.washington.edu
Green
Phil
P
D000818:Animals; D001483:Base Sequence; D001499:Bayes Theorem; D002415:Cats; D002417:Cattle; D004247:DNA / Q000235:genetics*; D004285:Dogs; D019143:Evolution, Molecular; D006736:Horses; D006801:Humans; D008390:Markov Chains; D051379:Mice; D008957:Models, Genetic; D009010:Monte Carlo Method; D009154:Mutation; D010802:Phylogeny; D011817:Rabbits; D051381:Rats; D013552:Swine; D014158:Transcription, Genetic / Q000235:genetics
D004247:DNA