MBE Advance Access published online on November 22, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl179
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, England; Graduate School of Biological, Medical and Veterinary Sciences, University of Cambridge, 17 Mill Lane, Cambridge CB2 1RX, England
* To whom correspondence should be addressed. 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 two 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. While 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.
Accepted November 15, 2006
Research Article
Estimating the Neutral Rate of Nucleotide Substitution Using Introns
Michael M. Hoffman 1 and Ewan Birney 2 *
2 EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, England
Ewan Birney, E-mail: birney{at}ebi.ac.uk
![]()
Abstract ![]()
CiteULike
Connotea
Del.icio.us What's this?
This article has been cited by other articles:
![]() |
M. Irimia and S. W. Roy Spliceosomal introns as tools for genomic and evolutionary analysis Nucleic Acids Res., March 1, 2008; 36(5): 1703 - 1712. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M. Resch, L. Carmel, L. Marino-Ramirez, A. Y. Ogurtsov, S. A. Shabalina, I. B. Rogozin, and E. V. Koonin Widespread Positive Selection in Synonymous Sites of Mammalian Genes Mol. Biol. Evol., August 1, 2007; 24(8): 1821 - 1831. [Abstract] [Full Text] [PDF] |
||||

