A coalescent model of background selection with recombination, demography and variation in selection coefficients

Abstract

There is increasing evidence that background selection, the effects of the elimination of recurring deleterious mutations by natural selection on variability at linked sites, may be a major factor shaping genome-wide patterns of genetic diversity. To accurately quantify the importance of background selection, it is vital to have computationally efficient models that include essential biological features. To this end, a structured coalescent procedure is used to construct a model of background selection that takes into account the effects of recombination, recent changes in population size and variation in selection coefficients against deleterious mutations across sites. Furthermore, this model allows a flexible organization of selected and neutral sites in the region concerned, and has the ability to generate sequence variability at both selected and neutral sites, allowing the correlation between these two types of sites to be studied. The accuracy of the model is verified by checking against the results of forward simulations. These simulations also reveal several patterns of diversity that are in qualitative agreement with observations reported in recent studies of DNA sequence polymorphisms. These results suggest that the model should be useful for data analysis.