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Bioinformatics. 2004 Aug 4;20 Suppl 1:i216-23.

A nucleotide substitution model with nearest-neighbour interactions.

Author information

  • 1Bioinformatics group, Department of Statistics, University of Oxford, Oxford, UK. lunter@stats.ox.ac.uk

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 substitution process.

PMID:
15262802
[PubMed - indexed for MEDLINE]
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