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MicroRNA target sites are often conserved among related species. On the other hand, purifying selection against novel microRNA target sites can also exist. However, the relative impact of conservation versus selection against target sites is still unknown. We investigated these processes in human populations by focusing on polymorphic sites in which one allele is a target site and the other is not. Target allele frequencies were significantly lower than expected at these sites. The analysis of derived allele frequencies revealed that, when the non-target allele is ancestral, the proportion of non-target sites is higher than expected by chance. Conversely, when the target allele is ancestral, the proportion of non-target alleles is also significantly higher than expected. These analyses reveal a selective pressure against microRNA target alleles, which is more effective than selection to conserve target sites. Additionally, microRNA target sites show relatively low levels of population differentiation (Fst). However, when we analyse separately target sites in which the target allele is ancestral in the population, the proportion of SNPs with high Fst significantly increases. These findings support a scenario in which population differentiation (and possible local adaptation) is much more likely in target sites that are lost than in the gain of new target sites.Taking all the results together, we conclude that there is evidence of pervasive selection against microRNA target sites in human populations. The overall impact across untranslated regions is not negligible and should be taken into account when studying the evolution of genomic sequences.
MicroRNA target sites are often conserved among related species. On the other hand, purifying selection against novel microRNA target sites can also exist. However, the relative impact of conservation versus selection against target sites is still unknown. We investigated these processes in human populations by focusing on polymorphic sites in which one allele is a target site and the other is not. Target allele frequencies were significantly lower than expected at these sites. The analysis of derived allele frequencies revealed that, when the non-target allele is ancestral, the proportion of non-target sites is higher than expected by chance. Conversely, when the target allele is ancestral, the proportion of non-target alleles is also significantly higher than expected. These analyses reveal a selective pressure against microRNA target alleles, which is more effective than selection to conserve target sites. Additionally, microRNA target sites show relatively low levels of population differentiation (Fst). However, when we analyse separately target sites in which the target allele is ancestral in the population, the proportion of SNPs with high Fst significantly increases. These findings support a scenario in which population differentiation (and possible local adaptation) is much more likely in target sites that are lost than in the gain of new target sites.Taking all the results together, we conclude that there is evidence of pervasive selection against microRNA target sites in human populations. The overall impact across untranslated regions is not negligible and should be taken into account when studying the evolution of genomic sequences.
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