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Proportionally more deleterious genetic variation in European than in African Dooulations

机译：欧洲人的遗传变异比非洲人更有害

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Quantifying the number of deleterious mutations per diploid human genome is of crucial concern to both evolutionary and medical geneticists. Here we combine genome-wide polymorphism data from PCR-based exon resequencing, comparative genomic data across mammalian species, and protein structure predictions to estimate the number of functionally consequential single-nucleotide polymorphisms (SNPs) carried by each of 15 African American (AA) and 20 European American (EA) individuals. We find that AAs show significantly higher levels of nudeotide hetero-zygosity than do EAs for all categories of functional SNPs considered, including synonymous, non-synonymous, predicted 'benign', predicted 'possibly damaging' and predicted 'probably damaging' SNPs. This result is wholly consistent with previous work showing higher overall levels of nucleotide variation in African populations than in Europeans. EA individuals, in contrast, have significantly more genotypes homozygous for the derived allele at synonymous and non-synonymous SNPs and for the damaging allele at 'probably damaging' SNPs than AAs do. For SNPs segregating only in one population or the other, the proportion of non-synonymous SNPs is significantly higher in the EA sample (55.4%) than in the AA sample (47.0%; P < 2.3 × 10~(-37)). We observe a similar proportional excess of SNPs that are inferred to be 'probably damaging' (15.9%inEA;12.1%inAA;P < 3.3 × 10~(-11)). Using extensive simulations, we show that this excess proportion of segregating damaging alleles in Europeans is probably a consequence of a bottleneck that Europeans experienced at about the time of the migration out of Africa.
机译：量化每个二倍体人类基因组的有害突变数是进化论者和医学遗传学家都至关重要的问题。在这里，我们将基于PCR的外显子重测序的全基因组多态性数据，哺乳动物物种的比较基因组数据以及蛋白质结构预测相结合，以估计15个非裔美国人（AA）各自携带的功能性单核苷酸多态性（SNP）的数量和20个欧美人（EA）。我们发现，对于所考虑的所有功能性SNP，包括同义，非同义，预测的“良性”，预测的“可能破坏”和预测的“可能破坏”的SNP，AA均比EA显着提高了核苷酸的杂合度水平。这一结果与以前的工作完全一致，后者显示非洲人群中核苷酸变异的总体水平高于欧洲人群。相比之下，与AA相比，EA个体对同义和非同义SNP处的衍生等位基因和“可能破坏” SNP处的破坏等位基因具有更多的纯合基因型。对于仅在一个种群或另一种群中分离的SNP，EA样本（55.4％）中非同义SNP的比例显着高于AA样本（47.0％； P <2.3×10〜（-37））。我们观察到类似比例的SNP被推断为“可能具有破坏性”（EA中为15.9％； AA中为12.1％； P <3.3×10〜（-11））。通过广泛的模拟，我们证明了欧洲人中过多的分离破坏性等位基因可能是欧洲人大约在移出非洲时经历的瓶颈的结果。

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