PT - JOURNAL ARTICLE AU - Raul Torres AU - Zachary A. Szpiech AU - Ryan D. Hernandez TI - Human demographic history has amplified the effects background selection across the genome AID - 10.1101/181859 DP - 2017 Jan 01 TA - bioRxiv PG - 181859 4099 - http://biorxiv.org/content/early/2017/08/29/181859.short 4100 - http://biorxiv.org/content/early/2017/08/29/181859.full AB - Natural populations often grow, shrink, and migrate over time. Demographic processes such as these can impact genome-wide levels of genetic diversity. In addition, genetic variation in functional regions of the genome can be altered by natural selection, which drives adaptive mutations to higher frequency or purges deleterious ones. Such selective processes impact not only the sites directly under selection but also nearby neutral variation through genetic linkage. While there is extensive literature examining the impact of linked selection (i.e., genetic hitchhiking in the context of positive selection and background selection in the context of deleterious variants) at demographic equilibrium, less is known about how non-equilibrium demographic processes impact patterns of linked selection. Utilizing a global sample of human whole-genome sequences from the Thousand Genomes Project and extensive simulations, we investigate how non-equilibrium demographic processes magnify and dampen the consequences of background selection (BGS) across the human genome. We observe that, compared to Africans, non-African populations have experienced larger proportional decreases in neutral genetic diversity in regions of strong BGS. We replicate these findings in admixed populations by showing that non-African ancestral components of the genome have been impacted more severely in regions of strong BGS. We attribute these differences to the strong population bottlenecks that non-Africans experienced as they migrated out of Africa and throughout the globe. Furthermore, we observe a strong correlation between FST and BGS, suggesting a stronger rate of genetic drift in regions of strong BGS. Forward simulations of human demographic history and BGS support these observations. Our results show that non-equilibrium demography significantly alters the consequences of BGS and support the need for more work investigating the dynamic process of multiple evolutionary forces operating in concert.Author summary Patterns of genetic diversity within a species are impacted at broad and fine scales by population size changes (“demography”) and natural selection. From both population genetics theory and observation of genomic sequence data, it is known that population size changes can impact genome-wide average neutral genetic diversity. Additionally, natural selection can impact neutral genetic diversity regionally across the genome through the process of linked selection. During this process, natural selection acting on adaptive or deleterious variants in the genome will also impact diversity at linked neutral sites. However, less is known about the dynamic changes to diversity that occur in regions impacted by linked selection when a population undergoes a size change. We characterize these dynamic changes using human sequence data, focusing on regions of the genome experiencing linked selection that is caused by deleterious variation (called “background selection”). We find that the population size changes experienced by humans have shaped the consequences of linked selection in the human genome. In particular, population contractions, such as those experienced by non-Africans, have disproportionately decreased neutral diversity in regions of the genome experiencing strong BGS, resulting in large differences between African and non-African populations.