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Synonymous and nonsynonymous rate variation in nuclear genes of mammals

A maximum likelihood approach was used to estimate the synonymous and nonsynonymous substitution rates in 48 nuclear genes from primates, artiodactyls, and rodents. A codon-substitution model was assumed, which accounts for the genetic code structure, transition/transversion bias, and base frequency biases at codon positions. Likelihood ratio tests were applied to test the constancy of nonsynonymous to synonymous rate ratios among branches (evolutionary lineages). It is found that at 22 of the 48 nuclear loci examined, the nonsynonymous/synonymous rate ratio varies significantly across branches of the tree. The result provides strong evidence against a strictly neutral model of molecular evolution. Our likelihood estimates of synonymous and nonsynonymous rates differ considerably from previous results obtained from approximate pairwise sequence comparisons. The differences between the methods are explored by detailed analyses of data from several genes. Transition/transversion rate bias and codon frequency biases are found to have significant effects on the estimation of synonymous and nonsynonymous rates, and approximate methods do not adequately account for those factors. The likelihood approach is preferable, even for pairwise sequence comparison, because morerealistic models about the mutation and substitution processes can be incorporated in the analysis.

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1. Ziheng Yang

   Present address: Department of Biology, University College London, 4 Stephenson Way, NW1 2HE, London, England

2. Rasmus Nielsen

   Present address: The Museum of Comparative Zoology, 3rd floor, Harvard University, 26 Oxford Street, 02138, Cambridge, MA, USA

1. Department of Integrative Biology, University of California, 94720-3140, Berkeley, California, USA

   Ziheng Yang & Rasmus Nielsen

2. Department of Biology, University College London, 4 Stephenson Way, NW1 2HE, London, England

   Ziheng Yang

1. Ziheng Yang
2. Rasmus Nielsen

Yang, Z., Nielsen, R. Synonymous and nonsynonymous rate variation in nuclear genes of mammals. J Mol Evol 46, 409–418 (1998). https://doi.org/10.1007/PL00006320

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• Received: 17 May 1997

• Accepted: 28 September 1997

• Issue Date: April 1998

• DOI: https://doi.org/10.1007/PL00006320

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