BACKGROUND It is well known that the effective size of a population (Ne) is one of the major determinants of the amount of genetic variation within the population. However, it is unclear whether the types of genetic variations are also dictated by the effective population size. To examine this, we obtained whole genome data from over 100 populations of the world and investigated the patterns of mutational changes. RESULTS Our results revealed that for low frequency variants, the ratio of AT→GC to GC→AT variants (β) was similar across populations, suggesting the similarity of the pattern of mutation in various populations. However, for high frequency variants, β showed a positive correlation with the effective population size of the populations. This suggests a much higher proportion of high frequency AT→GC variants in large populations (e.g. Africans) compared to those with small population sizes (e.g. Asians). These results imply that the substitution patterns vary significantly between populations. These findings could be explained by the effect of GC-biased gene conversion (gBGC), which favors the fixation of G/C over A/T variants in populations. In large population, gBGC causes high β. However, in small populations, genetic drift reduces the effect of gBGC resulting in reduced β. This was further confirmed by a positive relationship between Ne and β for homozygous variants. CONCLUSIONS Our results highlight the huge variation in the types of homozygous and high frequency polymorphisms between world populations. We observed the same pattern for deleterious variants, implying that the homozygous polymorphisms associated with recessive genetic diseases will be more enriched with G or C in populations with large Ne (e.g. Africans) than in populations with small Ne (e.g. Europeans).

中文翻译：

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种群大小影响人类核苷酸变异的类型。

背景技术众所周知，种群的有效大小（Ne）是种群内遗传变异量的主要决定因素之一。但是，尚不清楚遗传变异的类型是否也由有效种群规模决定。为了检验这一点，我们从世界上100多个种群中获得了全基因组数据，并研究了突变变化的模式。结果我们的结果表明，对于低频变异体，AT→GC与GC→AT变异体（β）的比率在不同人群之间相似，这表明不同人群中突变模式的相似性。但是，对于高频变体，β与群体的有效群体大小呈正相关。这表明在大量人群中高频AT→GC变体的比例要高得多（例如 非洲人）与人口较少的人（例如亚洲人）相比。这些结果表明，不同人群之间的替代模式差异很大。这些发现可以用偏向GC的基因转换（gBGC）的作用来解释，gBGC相对于A / T变异在人群中更倾向于固定G / C。在大量人群中，gBGC导致高β。但是，在少数人群中，遗传漂移会降低gBGC的作用，从而导致β值降低。对于纯合变体，Ne和β之间的正相关性进一步证实了这一点。结论我们的结果突出了世界人群之间纯合子类型和高频多态性的巨大差异。对于有害变体，我们观察到了相同的模式，