The Effects of Background Selection and Demography on Patterns of Neutral Variation within the Genome

Patterns of genetic diversity across the genome are affected by multiple forces of evolution, including natural selection and population demography. These effects are manifested both locally across the genome and genome-wide. While natural selection operates directly on only a small percentage of mutations within genome, it can have wide effects across neutral regions due to genetic linkage. In the context of purifying selection at linked sites, this process is called 'background selection' (BGS) and it leads to decreases in genetic diversity and skews the distribution of allele frequencies in the genome. While much theoretical and empirical investigation has gone into how BGS and demography operate independently to affect the genome, little investigation has been conducted on how these forces pattern the genome in concert. Utilizing thousands of human genomes and population genetic simulations, I have determined that the effects of BGS in humans can be magnified by population demography. I also analyzed population genetic simulations of different demographic models with BGS and found that the effects of demography and BGS are transient through time, with dips and rises in genetic diversity dependent on how far removed they are from a demographic event. Finally, in order to gain an understanding of how BGS and recent human population growth have affected patterns of the allele frequency spectrum, I analyzed genomes of varying sample size as a function of the strength of BGS. Doing so, I found that the effect of BGS on skewing the allele frequency spectrum towards rare variants in humans is dependent on sample size and leads to larger biases in demographic inference when sample size is small