title: Estimating the neutral rate of nucleotide substitution using introns.
abstract: Evolutionary biologists frequently rely on estimates of the neutral rate of evolution when characterizing the selective pressure on protein-coding genes. We introduce a new method to estimate this value based on intron nucleotide substitutions. The new method uses a metascript model that considers alternative splicing forms and an algorithm to pair orthologous introns, which we call Introndeuce. We compare the intron method with a widely used method that uses observed substitutions in synonymous coding nucleotides, by using both methods to estimate the neutral rate for human-dog and mouse-rat comparisons. The estimates of the 2 methods correlate strongly (r(S) = 0.75), but cannot be considered directly equivalent. We also investigate the effect of alignment error and G + C content on the variance in the intron method: in both cases there is an effect, and it is species-pair specific. Although the intron method may be more useful for shorter evolutionary distances, it is less useful at longer distances due to the poor alignment of less-conserved positions.
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, England.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Hoffman
authors.forename: Ewan
authors.initials: E
authors.lastname: Birney
mesh_terms: D000465:Algorithms; D000818:Animals; D001482:Base Composition; D005075:Biological Evolution; D004285:Dogs; D019143:Evolution, Molecular; D006801:Humans; D007438:Introns; D051379:Mice; D008957:Models, Genetic; D010802:Phylogeny; D017354:Point Mutation; D022821:RNA Splice Sites; D051381:Rats; D012641:Selection, Genetic
chemical_list: D022821:RNA Splice Sites