Journal of Molecular Evolution

, Volume 36, Issue 1, pp 96–99 | Cite as

Unbiased estimation of the rates of synonymous and nonsynonymous substitution

  • Wen-Hsiung Li
Letter To The Editor


The current convention in estimating the number of substitutions per synonymous site (K S ) and per nonsynonymous site (K A ) between two protein-coding genes is to count each twofold degenerate site as one-third synonymous and two-thirds nonsynonymous because one of the three possible changes at such a site is synonymous and the other two are nonsynonymous. This counting rule can considerably overestimate theK S value because transitional mutations tend to occur more often than transversional mutations and because most transitional mutations at twofold degenerate sites are synonymous. A new method that gives unbiased estimates is proposed. An application of the new and the old method to 14 pairs of mouse and rat genes shows that the new method gives aK S value very close to the number of substitutions per fourfold degenerate site whereas the old method gives a value 30% higher. Both methods give aK A value close to the number of substitutions per nondegenerate site.

Key words

Transition Transversion Synonymous rate Nonsynonymous rate Estimation methods 


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Copyright information

© Springer-Verlag New York Inc 1993

Authors and Affiliations

  • Wen-Hsiung Li
    • 1
  1. 1.Center for Demographic and Population GeneticsUniversity of TexasHoustonUSA

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