title: A nucleotide substitution model with nearest-neighbour interactions.
abstract: BACKGROUND
  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.
authors.affiliation: Bioinformatics group, Department of Statistics, University of Oxford, Oxford, UK. lunter@stats.ox.ac.uk
authors.forename: Gerton
authors.initials: G
authors.lastname: Lunter
authors.forename: Jotun
authors.initials: J
authors.lastname: Hein
mesh_terms: D000465:Algorithms; D000818:Animals; D020137:Base Pair Mismatch / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D009711:Nucleotides / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D009711:Nucleotides; D004247:DNA