Pattern of synonymous and nonsynonymous substitutions: An indicator of mechanisms of molecular evolution

Comparison of numbers of synonymous and nonsynonymous substitutions is useful for understanding mechanisms of molecular evolution. In this paper, I examine the statistical properties of six methods of estimating numbers of synonymous and nonsynonymous substitutions. The six methods are Miyata and Yasunaga's (MY) method; Nei and Gojobori's (NG) method; Li, Wu and Luo's (LWL) method; Pamilo, Bianchi and Li's (PBL) method; and Ina's (Ina) two methods. When the transition/transversion bias at the mutation level is strong, the numbers of synonymous and nonsynonymous substitutions are estimated more accurately by the PBL and Ina methods than by the NG, MY and LWL methods. When the nucleotide-frequency bias is strong and distantly related sequences are compared, all the six methods give underestimates of the number of synonymous substitutions. The concept of synonymous and nonsynonymous categories is also useful for analysis of DNA polymorphism data.