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In an interesting piece of work, Sung et al. (1) proposed that population size is a major factor determining mutation rate. However, as reported previously (2, 3), mutation rates are expected to negatively scale with proteome size (the total number of codons in a genome; P) with an exponent of −1, assuming that the coding DNA in a genome exerts a constraint on genetic fidelity. The influence of proteome size was originally termed the “proteomic constraint,” and was proposed to affect a variety of aspects of genetic fidelity in addition to mutation rates (3). The following relationship was derived: where μ is mutation rate, and C is the …

Proteome size as the major factor determining mutation rates