DNA sequence evolution with neighbor-dependent mutation

We introduce a model of DNA sequence evolution which can account for biases in mutation rates that depend on the identity of the neighboring bases. An analytic solution for this class of models is developed by adopting well-known methods of nonlinear dynamics. Results are presented for the CpG-methylation-deamination process, which dominates point substitutions in vertebrates. The dinucleotide frequencies generated by the model (using empirically obtained mutation rates) match the overall pattern observed in noncoding DNA. A web-based tool has been constructed to compute single- and dinucleotide frequencies for arbitrary neighbor-dependent mutation rates. Also provided is the backward procedure to infer the mutation rates using maximum likelihood analysis given the observed singleand dinucleotide frequencies. Reasonable estimates of the mutation rates can be obtained very ef ciently, using generic noncoding DNA sequences as input, after masking out long homonucleotide subsequences. Ou...

• Type: Conference
• Year: 2002
• Where: RECOMB
• Authors: Peter F. Arndt, Christopher B. Burge, Terence Hwa
• Keywords: Computational Biology, Dinucleotide Frequencies, Maximum Likelihood Analysis, Mutation Rates, RECOMB 2002