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Evolutionary dynamics of microRNA target sites across vertebrate evolution

机译：脊椎动物演化中微瘤靶位点的进化动态

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MicroRNAs (miRNAs) control the abundance of the majority of the vertebrate transcriptome. The recognition sequences, or target sites, for bilaterian miRNAs are found predominantly in the 3′ untranslated regions (3′UTRs) of mRNAs, and are amongst the most highly conserved motifs within 3′UTRs. However, little is known regarding the evolutionary pressures that lead to loss and gain of such target sites. Here, we quantify the selective pressures that act upon miRNA target sites. Notably, selective pressure extends beyond deeply conserved binding sites to those that have undergone recent substitutions. Our approach reveals that even amongst ancient animal miRNAs, which exert the strongest selective pressures on 3′UTR sequences, there are striking differences in patterns of target site evolution between miRNAs. Considering only ancient animal miRNAs, we find three distinct miRNA groups, each exhibiting characteristic rates of target site gain and loss during mammalian evolution. The first group both loses and gains sites rarely. The second group shows selection only against site loss, with site gains occurring at a neutral rate, whereas the third loses and gains sites at neutral or above expected rates. Furthermore, mutations that alter the strength of existing target sites are disfavored. Applying our approach to individual transcripts reveals variation in the distribution of selective pressure across the transcriptome and between miRNAs, ranging from strong selection acting on a small subset of targets of some miRNAs, to weak selection on many targets for other miRNAs. miR-20 and miR-30, and many other miRNAs, exhibit broad, deeply conserved targeting, while several other comparably ancient miRNAs show a lack of selective constraint, and a small number, including mir-146, exhibit evidence of rapidly evolving target sites. Our approach adds valuable perspective on the evolution of miRNAs and their targets, and can also be applied to characterize other 3′UTR regulatory motifs.
机译：microRNA（miRNA）控制大多数脊椎动物转录组的丰富。识别序列或靶位位点主要在3'未翻译的区域（3'UTRS）的MRNA中发现，并且是3'UTR中最高度保守的主题。然而，关于导致这种靶位点的损失和增益的进化压力很少。在这里，我们量化了对miRNA靶位点作用的选择性压力。值得注意的是，选择性压力超越深受保守的结合位点，对最近的取代的那些。我们的方法揭示了即使在古代动物miRNA中，在3'UTR序列上发挥着最强的选择性压力，MiRNA之间的靶位点演变的模式存在显着差异。考虑到古代动物miRNA，我们发现三个不同的miRNA群体，每组各自展示哺乳动物进化期间的目标网站增益和损失的特征率。第一组既不很少丢失和收益。第二组仅显示选择对现场丢失的选择，现场增益发生在中性率，而第三个丢失并在中性或高于预期的速率下获得网站。此外，改变现有靶位部位强度的突变是不歧视的。将我们的方法应用于单个转录物揭示了在转录组上的选择性压力分布的变化，并在miRNA之间，从一些miRNA的小靶的强烈选择作用，对其他miRNA的许多靶标的弱化。 MiR-20和MiR-30，以及许多其他MiRNA，展示广泛的，深受保守的靶向，而其他几个古代MiRNA缺乏选择性约束，并且包括MIR-146的少数，展示了快速发展的目标网站的证据。我们的方法在MiRNA及其目标的演变中增加了有价值的视角，也可以应用于表征其他3'URR监管主题。

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