Is the synonymous substitution rate in mammals gene-specific?

摘要

There is a great deal of variation in silent rates of evolution (Ks) between genes in the same species pair comparison (Bernardi, Mouchiroud, and Gautier 1993; Wolfe and Sharp 1993; Mouchiroud, Gautier, and Bernardi 1995). This may represent random fluctuation (Kumar and Subramanian 2002) or may be deterministically caused. Evidence for the latter comes from the finding that the rate of silent site evolution of a gene is repeatable across independent lineages (Bulmer, Wolfe, and Sharp 1991; Mouchiroud, Gautier, and Bernardi 1995; Bielawski, Dunn, and Yang 2000). Most notably, Mouchiroud, Gautier, and Bernardi (1995) found that the number of synonymous substitutions per synonymous site (Ks) for a gene in the human-cow comparison was a very strong predictor of the Ks of the same gene in the mouse-rat comparison. This repeatability has been used as evidence (Mouchiroud, Gautier, and Bernardi 1995) for selection acting upon silent sites in orthologous genes. One argument holds, for example, that if purifying selection favors a particular amino acid at a given site, it should also favor the translationally most accurate codon and codon usage bias would be selected for. The repeatability of Ks and the Ka-Ks correlation are then attributed to the same selectionist cause. However, this interpretation is questionable on a number of counts. Most notably, with one possible exception (Debry and Marzluff 1994), there is no compelling evidence that codon usage bias in mammals is the result of selection (Eyre-Walker 1991; Karlin and Mrazek 1996; Urmtia and Hurst 2001). Alternative interpretations of the putative fact are also possible. These include gene- or chromosome-specific mutation rates and gene-specific rates of biased gene conversion, all of which could give repeatable Ks and a Ka-Ks correlation.