Rates of nucleotide substitution are evidently higher in rodents than in man.
Authors: W H Li, C I Wu
Journal: Molecular Biology and Evolution (1987)

In a comparative study of the DNA sequences of a variety of mammalian genes, we concluded that rodents (rat and mouse) have accumulated significantly more nucleotide substitutions than has man since the rodent-primate split (Wu and Li 1985).Easteal ( 1985) challenges our conclusion and maintains that our results are compatible with the rate-constancy hypothesis.We compared the rates of nucleotide substitution in rodents and man using the relative-rate test.For each of the 12 genes considered, we used cow, goat, pig, dog, or rabbit as a reference species.We obtained the results shown in table 1.We assumed that man and rodents are more closely related to each other than either is to the reference species (fig. 1 a).This phylogenetic scheme implies the following approximate numbers of substitutions per fourfold-degenerate site in the three branches of the phylogenetic tree: man, 0.2; rodents, 0.4; reference, 0.2.From these calculations, we concluded that at fourfold-degenerate sites rodent genes have evolved two times faster than human genes.Easteal contends that the alternative explanation shown in figure 1 b is equally plausible and can be taken as evidence that substitutions have occurred at a constant rate in all species.In our paper we stated that our results cannot be explained by this alternative evolutionary scheme.Our reason, not explicitly stated, was that this scheme assumes that the divergence time between man and the reference species is only two-thirds (27'/3) of the divergence time (T) between man and rodents.We point out below two serious difficulties with Easteal's explanation.First, under Easteal's evolutionary scheme (fig. 1 b), the rate-constancy hypothesis does not hold for nonsynonymous substitutions.For example, from table 1 we can show that at nondegenerate sites the numbers of substitutions per site are 0.075 for the human branch, 0.075 for the reference branch, and 0.095 for the rodent branch.Therefore, the rates of substitution per nondegenerate site per unit time are 0.0751 (27'/3) = O.l13/Tfor the human branch andO.O95/(T+ T/3) = O.O71/Tfor the rodent branch, the former rate being 1.6 times higher than the latter.Obviously, this is contradictory to Easteal's contention that our results support the rate-constancy hypothesis.The only way to salvage the rate-constancy hypothesis is to assume that the divergence time between man and the reference species is somewhere between 2T/3 and T. The best choice seems to be 0.8T, under which the rate of substitution per nondegenerate site is 1.2 times higher in man than in rodents while the rate of substitution per fourfold-degenerate site is 1.3 times higher in rodents than in man.But this evolutionary scheme is not compatible with the mammalian fossil record (see below).Second, Easteal's evolutionary scheme (fig. 1 b) is at variance with the mammalian fossil record.Primates and rodents are thought to have diverged -75 Myr ago.Thus, Easteal's assumption would imply that primates and artiodactyls (or carnivores) diverged only 50 Myr ago.This is contradictory to the general belief that primates, artiodactyls, and carnivores have been distinct since late in the Mesozoic, i.e., at least