Background selection and biased gene conversion affect more than 95% of the human genome and bias demographic inferences

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.

将自然选择对基因组多样性的影响与种群历史动态的影响分离开来，向来是一项极具挑战性的工作，但却是准确重建物种演化历史的必要前提。本研究使用高质量的人类基因组数据，证实了连锁位点上的纯化选择（即背景选择（background selection, BGS））与GC偏好性基因转换（GC-biased gene conversion, gBGC）二者共同作用，可影响人类基因组中多达95%的变异位点。我们发现，背景选择与GC偏好性基因转换的作用强度及相对重要性，主要由重组率与碱基组成的差异所决定。值得注意的是，同义位点（synonymous sites）与非转录区域（non-transcribed regions）同样会受到这两种过程的影响，尽管影响程度各不相同。若将此类区域用于种群历史推断（demographic inference），可能会引入显著的偏差。不过，通过选取重组率高于1.5 cM/Mb的基因组区域，并限定突变类型为C↔G、A↔T，我们鉴定得到了一组单核苷酸多态性（Single Nucleotide Polymorphisms, SNPs），这类位点基本不受背景选择或GC偏好性基因转换的影响，从而能够规避人类历史重建过程中的此类偏差。