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Population size influences the type of nucleotide variations in humans
Journal article   Open access   Peer reviewed

Population size influences the type of nucleotide variations in humans

Sankar Subramanian
BMC Genetics, Vol.20, 93
2019
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https://doi.org/10.1186/s12863-019-0798-9View
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Abstract

type of nucleotide change biased gene conversion recombination common and rare variants deleterious variants population bottleneck and human genomes
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).

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