The Rates of Nucleotide Substitution in the Human and Rodent Lineages: A Reply to Li and Wu
Authors: Simon Easteal
Journal: Molecular Biology and Evolution (1987)

Li and Wu (1986), in responding to my discussion (Easteal 1985) of their earlier paper (Wu and Li 1985), make some points that require further comment.First, I suggested that the phylogenetic scheme assumed by Wu and Li in their relative-rate test was not firmly supported by the fossil record.Li and Wu argue that an alternative scheme, which I suggested, is at variance with the generally accepted view of eutherian evolution.They fail to point out, however, that there is great diversity of opinion about the branching order of the major eutherian lineages.Many of the schemes that have been proposed are reviewed by Szalay (1977), whose own analysis of the morphology of extant taxa suggests that the species are related in the order that I suggested (with the exception that he considers rabbits to be close relatives of rodents).It is worth noting that this scheme is in broad agreement with the pattern of conservation of linkage groups (Womack and Moll 1986) and with the comparison of the nucleotide sequences of mitochondrial genomes (Hasegawa et al. 1985).Li and Wu contend that even if their assumed branching order is not correct, the potential errors in divergence times are too small to account for the differences in substitution rate.Divergence times, however, are no less subject to varied interpretation than are branching orders.Views have changed, theories are disputed, discussions are tempered by cautionary comments, and the data are few (Clemens et al. 1979; Kielan-Jaworowska et al. 1979;Szalay and Delson, 1979;Novacek, 1982).Furthermore, the fossil record provides evidence only of morphological divergence, but phylogenetic divergence does not necessarily occur at the same time as morphological divergence (Wake et al. 1983).Even if the potential for error in estimates of the morphological divergence times were as small as Li and Wu suggest, this would not mean that the potential for error in phylogenetic divergence time estimates is also small.It is possible that the taxa being compared diverged from each other either more recently or at a much earlier time than has been supposed.Second, Wu and Li's ( 1985) original analysis of paralogous genes is broadly consistent with a substitution-rate difference between human and mouse lineages.There are, however, some anomalies (Easteal 1985, table 2).I proposed a scheme, involving gene conversion, to explain these.The scheme requires the existence of a mouse globin gene more distantly related to the mouse E and F genes than are the mouse and human A genes.Li and Wu suggest that no such gene exists.They are correct that there is no known gene with a greater degree of nucleotide sequence difference but not that there is no more distantly related gene.There is evidence for such a gene-the Bh3 pseu; dogene.Hutchison et al. (1984) have shown that the Bh3 gene is probably homologous to primate &globin genes and that it has been converted by mouse P-globin genes since the primate-rodent split.The &globin gene appears to have experienced similar exchanges with the adult P-globin gene in man and with an E-or y-globin gene in lemurs (Jeffreys et al. 1982).The ancestral &globin gene also appears to have diverged 1.