A coalescent dual process for a Wright-Fisher diffusion with recombination and its application to haplotype partitioning

摘要

Duality plays an important role in population genetics. It can relate results from forwards-in-time models of allele frequency evolution with those of backwards-in-time genealogical models; a well known example is the duality between the Wright–Fisher diffusion for genetic drift and its genealogical counterpart, the coalescent. There have been a number of articles extending this relationship to include other evolutionary processes such as mutation and selection, but little has been explored for models also incorporating crossover recombination. Here, we derive from first principles a new genealogical process which is dual to a Wright–Fisher diffusion model of drift, mutation, and recombination. The process is reminiscent of the ancestral recombination graph , a widely-used multilocus genealogical model, but here ancestral lineages are typed and transition rates are regarded as being conditioned on an observed configuration at the leaves of the genealogy. Our approach is based on expressing a putative duality relationship between two models via their infinitesimal generators, and then seeking an appropriate test function to ensure the validity of the duality equation. This approach is quite general, and we use it to find dualities for several important variants, including both a discrete L-locus model of a gene and a continuous model in which mutation and recombination events are scattered along the gene according to continuous distributions. As an application of our results, we derive a series expansion for the transition function of the diffusion. Finally, we study in further detail the case in which mutation is absent. Then the dual process describes the dispersal of ancestral genetic material across the ancestors of a sample. The stationary distribution of this process is of particular interest; we show how duality relates this distribution to haplotype fixation probabilities. We develop an efficient method for computing such probabilities in multilocus models.udud