Background selection 20 years on: the Wilhelmine E. Key 2012 invitational lecture

The mutation process continually produces new deleterious variants at sites throughout the genome, which are then mostly eliminated by selection. This causes a reduction in variability at linked neutral or nearly neutral sites, as well as distortions of the genealogies of samples of alleles from a population. In regions of the genome where recombination is frequent, the effects of selection against deleterious mutations on variability and evolution at linked sites can be predicted under the assumption that most deleterious mutations have such large effects that their behavior in the population is effectively deterministic-this is background selection in the strict sense. But in genomic regions with little or no recombination, such as the Y chromosome, large departures from the predictions using deterministic models may occur, because of interference between different sites under selection. Evidence from Drosophila and human populations is discussed, which suggests that these processes play a major role in shaping patterns of DNA sequence variation and evolution, including the relative levels of variation on X chromosomes and autosomes, and the highly reduced variability seen in regions that lack crossing over.