Detecting Directional Selection from the Polymorphism Frequency Spectrum
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The distribution of genetic polymorphisms in a population contains information about the mutation rate and the strength of natural selection at a locus. Here, we show that the Poisson Random Field (PRF) method of population-genetic inference suffers from systematic biases that tend to underestimate selection pressures and mutation rates, and that erroneously infer positive selection. These problems arise from the infinite-sites approximation inherent in the PRF method. We introduce three new inference techniques that correct these problems. We present a finite-site modification of the PRF method, as well as two new methods for inferring selection pressures and mutation rates based on diffusion models. Our methods can be used to infer not only a "weighted average" of selection pressures acting on a gene sequence, but also the distribution of selection pressures across sites. We evaluate the accuracy of our methods, as well that of the original PRF approach, by comparison with Wright-Fisher simulations.