Population Dynamics of Sequence Variation

A polymorphism that occurs at considerable frequency in a population is likely to be very old (i.e., must have originated many generations ago). 

Population genetics has produced a detailed theory of the relationship between frequency, drift, and selective value of genetic variation (Nei, 1975 Hard and Clark, 1989 Li, 1997). The problem with its straightforward application is that the main parameters, such as history of population size, fixation rate, and selective pressure, are difficult to establish. 

The usual situation at a molecular site (such as a sequence position) is monomorphism (only one nucleotide present in the population) or biallelism. Multiallelism is rare. This fact can be explained by population dynamics over a large number of generations. When a variant is deleteri- 

The mutation rate fx of the nucleotide (or amino acid) at a sequence site is related to the popular notion of a molecular clock (Zuckerkandl and Pauling, 1965), because it determines after which time the clock ticks and anew mutation arises because of a copying error during meiosis. Whether this clock ticks uniformly is a topic of prolonged debate (summarized in Li, 1997). The question is usually treated by comparing sequence difference at (supposedly) neutral sites with evolutionary distance between species. 

In an extant population the heterozygosity at a given site may be measured. Under the neutral hypothesis and assuming that the mutation rate is sufficiently low, one may calculate the product 4Ne/x, which is in the numerical range of the expected heterozygosity. A typical nucleotide heterozygosity is in the range of 5/10,000, which implies that if /x is 10-9 or (10 8) then Ne is 500,000 (or 50,000, respectively). 

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