Abstract
Disentangling the effect on genomic diversity of natural selection from that of demography is notoriously difficult, but necessary to properly reconstruct the history of species. Here, we use high-quality human genomic data to show that purifying selection at linked sites (i.e. background selection, BGS) and GC-biased gene conversion (gBGC) together affect as much as 95% of the variants of our genome. We find that the magnitude and relative importance of BGS and gBGC are largely determined by variation in recombination rate and base composition. Importantly, synonymous sites and non-transcribed regions are also affected, albeit to different degrees. Their use for demographic inference can lead to strong biases. However, by conditioning on genomic regions with recombination rates above 1.5 cM/Mb and mutation types (C↔G, A↔T), we identify a set of SNPs that is mostly unaffected by BGS or gBGC, and that avoids these biases in the reconstruction of human history. more
Highlights
Human genomic diversity has evolved under diverse and complex constraints (Auton et al, 2015), such as past demography, selection, mutations, or genomic rearrangements (Lohmueller et al, 2011; Schiffels and Durbin, 2014; Sudmant et al, 2015; Mallick et al, 2016)
We show in the Materials and methods below how this statistic depends on the average time to the most recent common ancestor of the whole sample, and, if one assumes neutrality that this statistic should be the same on expectation for any individual in the sample across its whole genome, irrespective of the particular demography of its population (Figure 1—figure supplement 1)
We have interpreted the striking linear relationship observed between derived allele frequency per individual (DAFi) and recombination rate (Figure 1) as evidence for the pervasive effect of background selection (BGS) but other processes could in principle lead to a similar relationship
Summary
Human genomic diversity has evolved under diverse and complex constraints (Auton et al, 2015), such as past demography, selection, mutations, or genomic rearrangements (Lohmueller et al, 2011; Schiffels and Durbin, 2014; Sudmant et al, 2015; Mallick et al, 2016). The influence of these evolutionary forces and their interactions remain to be fully understood It is yet unclear which fraction of the genome evolves under positive or purifying selection (McVicker et al, 2009; Rands et al, 2014; Corbett-Detig et al, 2015). Such information is crucial to our understanding of what portion of the genome is evolving neutrally, and necessary to form a clear basis for demographic inference, the detection of selective events, or the inference of the distribution of fitness effects of new mutations. While a direct mutagenic effect of recombination seems unlikely (McVicker et al, 2009; Schaibley et al, 2013) except at CpG sites
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