A Bayesian method for jointly estimating allele age and selection intensity

Abstract

Summary: The problem of jointly estimating the intensity of past selection affecting an allele and the allele's age is formulated in a Bayesian framework. The prior distribution of allele age given its frequency is obtained from existing population genetics theory. The prior distribution of selection intensity is assumed to reflect the fact that positive selection on a new mutant is more likely to be weak than strong. The general approach is illustrated by the development of an importance sampling method applicable to low-frequency alleles. This method can be used either when the haplotypes of closely linked marker loci are known or when the lengths of linked ancestral chromosomal segments can be inferred. The method is illustrated with an application to the A− allele of G6PD in Africa. Because changes in allele frequency and recombination are both intrinsically stochastic, there are limits to the accuracy achievable with any method.