Abstract
BackgroundIt 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.ResultsOur 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.ConclusionsOur 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).
Highlights
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
We have shown that the types of Single Nucleotide Variation (SNV) observed in different human populations are very likely to be modulated by their effective population sizes
Since this pattern was universal for genome-wide variations we showed that deleterious SNVs follow this pattern
Summary
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. The out of Africa hypothesis predicts that the ancestors of the human populations around the world originated in Africa, migrated out of the continent and eventually colonized different parts of the world [1] During this process, the ancestral populations underwent a series of population bottlenecks along the migratory routes. Previous empirical studies confirmed this prediction and showed that populations in Africa are the most genetically diverse and that the diversity declined with increasing geographic distance from Africa along the colonization routes [2,3,4,5,6] Since mutation rate is similar across human populations, the observed difference in the diversity of world populations is largely due to the variations in effective population sizes. A → G or T → C) similar across populations? This question arises from our understanding of the phenomenon of GCbiased gene conversion (gBGC)
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