A nucleotide substitution model with nearest-neighbour interactions

Authors:
Gerton Lunter;Jotun Hein
Affiliations:
Bioinformatics group, Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK;Bioinformatics group, Department of Statistics, University of Oxford, 1 South Parks Road, Oxford OX1 3TG, UK
Venue:
Bioinformatics
Year:
2004

Citing 0
Cited 2

Phylogenetics by likelihood: evolutionary modeling as a tool for understanding the genome

Journal of Biomedical Informatics - Special issue: Phylogenetic inferencing: Beyond biology
Brief communication: Comparative analysis of core promoter region: Information content from mono and dinucleotide substitution matrices

Computational Biology and Chemistry

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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.