Abstract

Motivation: It is well known that neighbouring nucleotides in DNA sequences do not mutate independently of each other. In this paper, we introduce a context-dependent substitution model and derive an algorithm to calculate the likelihood of sequences evolving under this model. We use this algorithm to estimate neighbour-dependent substitution rates, as well as rates for dinucleotide substitutions, using a Bayesian sampling procedure. The model is irreversible, giving an arrow to time, and allowing the position of the root between a pair of sequences to be inferred without using out-groups.

Results: We applied the model upon aligned human–mouse non-coding data. Clear neighbour dependencies were observed, including 17–18-fold increased

CpG
to
TpG
/
CpA
rates compared with other substitutions. Root inference positioned the root halfway the mouse and human tips, suggesting an approximately clock-like behaviour of the irreversible part of the subsitution process.

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To whom correspondence should be addressed.

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