Frozen Evolution. Or, that’s not the way it is, Mr. Darwin. A Farewell to Selfish Gene.

The frequency with which mutations are fixed in a certain position or in a given DNA section per time unit in evolution is called the substitution rate. This rate is generally expressed as the number of fixed mutations in the given position per year. The substitution rate must not be confused with the mutation rate; however, it can be concluded that these two rates are numerically equal for neutral mutations (see V.3.3). The mutation rate, i.e. the number of mutations occurring in the given position per time unit for all the members of the population, depends primarily on the accuracy of replication, the efficiency of reparation processes, the intensity of the action of mutagens and the mutability of the sequential motif in the given position of the DNA chain. In contrast, the substitution rate depends not only on the mutation rate at the given site, but also on the intensity and direction of selection that act on the mutation in the given position and in its vicinity. Simultaneously, the substitution rate for selectively neutral mutations does not depend on the size of the population (see V.3.3) (which suggests that genetic drift rather than genetic draft drives the DNA evolution in the studied populations). With growing population size, the number of newly formed mutations in a given position in the population increases linearly, i.e. the mutation rate linearly increases; however, simultaneously, there is a linear decrease in the probability that the newly formed mutation will be fixed by genetic drift.

It must be, however, emphasized that the percentage of mutations that fall in the category of selectively neutral does depend on the size of the population. It is not possible to draw a sharp line between selectively significant and selectively neutral mutations. Basically, only a minimum of them has a selection coefficient equal to zero; most mutations have a negative or positive selection coefficient. It is generally accepted that those mutations whose absolute selection coefficient value is less than 1/N_e, where N_e  is the effective size of the given population, act as effectively neutral in the given population. This means that a greater percentage of mutations fall in the category of effectively neutral mutations in a small population than in a large population. As most mutations have a negative selection coefficient and only a minority have a positive selection coefficient and because the probability of fixation of negative mutations is substantially smaller than the probability of fixation of positive or selectively neutral mutations, the total number of mutations fixed by drift over a time unit, i.e. the substitution rate, is greater in a small population than in a large population (see also V.5).