SHOULD WE EXPECT SUBSTITUTION RATE TO DEPEND ON POPULATION-SIZE

The rate of nucleotide substitution is generally believed to be a decr easing function of effective population size, at least for nonsynonymo us substitutions. This view was originally based on consideration of s lightly deleterious mutations with a fixed distribution of selection c oefficients. A realistic model must include the occurrence and fixatio n of some advantageous mutations that compensate for the loss of fitne ss due to deleterious substitutions. Some such models, such as so-call ed ''fixed'' models, also predict a population size effect on substitu tion rate. An alternative model, presented here, predicts the near abs ence of a population size effect on substitution rate. This model is b ased on concave log-fitness functions and a fixed distribution of muta tional effects on the selectively important trait. Simulations of an i nstance of the model confirm the approximate insensitivity of the subs titution rate to population size. Although much experimental evidence has been claimed to support the existence of a population size effect, the body of evidence as a whole is equivocal, and much of the evidenc e that is supposed to demonstrate such an effect would also suggest th at it is very small. Perhaps the proposed model applies well to some g enes and not so well to others, and genes therefore vary with regard t o the population size effect.