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Summary: JOURNAL OF COMPUTATIONAL BIOLOGY
Volume 10, Numbers 34, 2003
© Mary Ann Liebert, Inc.
Pp. 313322
DNA Sequence Evolution with
Neighbor-Dependent Mutation
PETER F. ARNDT,1
CHRISTOPHER B. BURGE,2
and TERENCE HWA1
ABSTRACT
We introduce a model of DNA sequence evolution which can account for biases in muta-
tion 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 em-
pirically 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 single-
and dinucleotide frequencies. Reasonable estimates of the mutation rates can be obtained
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