MicroRNA target sites are often conserved during evolution and purifying selection to maintain such sites is expected. On the other hand, comparative analyses identified a paucity of microRNA target sites in coexpressed transcripts, and novel target sites can potentially be deleterious. We proposed that selection against novel target sites pervasive. The analysis of derived allele frequencies revealed that, when the derived allele is a target site, the proportion of nontarget sites is higher than expected, particularly for highly expressed microRNAs. Thus, new alleles generating novel microRNA target sites can be deleterious and selected against. When we analyzed ancestral target sites, the derived (nontarget) allele frequency does not show statistical support for microRNA target allele conservation. We investigated the joint effects of microRNA conservation and expression and found that selection against microRNA target sites depends mostly on the expression level of the microRNA. We identified microRNA target sites with relatively high levels of population differentiation. However, when we analyze separately target sites in which the target allele is ancestral to the population, the proportion of single-nucleotide polymorphisms with high F_st significantly increases. These findings support that population differentiation is more likely in target sites that are lost than in the gain of new target sites. Our results indicate that selection against novel microRNA target sites is prevalent and, although individual sites may have a weak selective pressure, the overall effect across untranslated regions is not negligible and should be accounted when studying the evolution of genomic sequences.

中文翻译：

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针对人群中microRNA靶位点的普遍选择。

MicroRNA靶位点通常在进化过程中是保守的，并且期望纯化选择以维持此类位点。另一方面，比较分析发现共表达的转录本中的微RNA靶位点很少，而且新的靶位点可能有害。我们建议针对新型目标位点的选择无处不在。对衍生的等位基因频率的分析显示，当衍生的等位基因是靶位点时，非靶位点的比例比预期的要高，特别是对于高表达的microRNA。因此，产生新的微小RNA靶位点的新等位基因可能是有害的并且是针对其选择的。当我们分析祖先的目标位点时，派生的（非目标）等位基因频率并未显示出对microRNA目标等位基因保守性的统计支持。我们研究了microRNA保守和表达的联合效应，发现针对microRNA靶位点的选择主要取决于microRNA的表达水平。我们确定了相对较高的群体分化水平的microRNA目标站点。但是，当我们分别分析目标等位基因在人群中祖先的目标位点时，单核苷酸多态性比例较高F _st明显增加。这些发现支持在失去的目标地点比获得新的目标地点更有可能实现人口分化。我们的结果表明，针对新的microRNA靶位点的选择非常普遍，尽管单个位点的选择压力可能很弱，但跨非翻译区的总体作用却不可忽略，在研究基因组序列的进化时应予以考虑。