Estimating synonymous and nonsynonymous substitution rates under realisticevolutionary models

Citation
Zh. Yang et R. Nielsen, Estimating synonymous and nonsynonymous substitution rates under realisticevolutionary models, MOL BIOL EV, 17(1), 2000, pp. 32-43
Citations number
40
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology,"Experimental Biology
Journal title
MOLECULAR BIOLOGY AND EVOLUTION
ISSN journal
0737-4038 → ACNP
Volume
17
Issue
1
Year of publication
2000
Pages
32 - 43
Database
ISI
SICI code
0737-4038(200001)17:1<32:ESANSR>2.0.ZU;2-D
Abstract
Approximate methods for estimating the numbers of synonymous and nonsynonym ous substitutions between two DNA sequences involve three steps: counting o f synonymous and nonsynonymous sites in the two sequences, counting of syno nymous and nonsynonymous differences between the two sequences, and correct ing for multiple substitutions at the same site. We examine complexities in volved in those steps and propose a new approximate method that takes into account two major features of DNA sequence evolution: transition/transversi on rate bias and base/codon frequency bias. We compare the new method with maximum likelihood, as well as several other approximate methods, by examin ing infinitely long sequences, performing computer simulations, and analyzi ng a real data set. The results suggest that when there are transition/tran sversion rate biases and base/codon frequency biases, previously described approximate methods for estimating the nonsynonymous/synonymous rate ratio may involve serious biases, and the bias can be both positive and negative. The new method is, in general, superior to earlier approximate methods and may be useful for analyzing large data sets, although maximum likelihood a ppears to always be the method of choice.