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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 substitution process.

Original publication

DOI

10.1093/bioinformatics/bth901

Type

Journal article

Journal

Bioinformatics

Publication Date

04/08/2004

Volume

20 Suppl 1

Pages

i216 - i223

Keywords

Algorithms, Animals, Base Pair Mismatch, Chromosome Mapping, Computer Simulation, DNA, DNA Mutational Analysis, Genetic Variation, Humans, Mice, Models, Genetic, Nucleotides, Sequence Analysis, DNA