Comparison and content of the Wright-Fisher model of random genetic drift, the diffusion approximation, and an intermediate model.

We investigate the detailed connection between the Wright-Fisher model of random genetic drift and the diffusion approximation, under the assumption that selection and drift are weak and so cause small changes over a single generation. A representation of the mathematics underlying the Wright-Fisher model is introduced which allows the connection to be made with the corresponding mathematics underlying the diffusion approximation. Two 'hybrid' models are also introduced which lie 'between' the Wright-Fisher model and the diffusion approximation. In model 1 the relative allele frequency takes discrete values while time is continuous; in model 2 time is discrete and relative allele frequency is continuous. While both hybrid models appear to have a similar status and the same level of plausibility, the different nature of time and frequency in the two models leads to significant mathematical differences. Model 2 is mathematically inconsistent and has to be ruled out as being meaningful. Model 1 is used to clarify the content of Kimura's solution of the diffusion equation, which is shown to have the natural interpretation as describing only those populations where alleles are segregating. By contrast the Wright-Fisher model and the solution of the diffusion equation of McKane and Waxman cover populations of all categories, namely populations where alleles segregate, are lost, or fix.