2020
DOI: 10.1371/journal.pgen.1008285
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Evolutionary dynamics of microRNA target sites across vertebrate evolution

Abstract: 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 0 untranslated regions (3 0 UTRs) of mRNAs, and are amongst the most highly conserved motifs within 3 0 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 e… Show more

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Cited by 42 publications
(33 citation statements)
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“…The low variability of miRNA genes, a feature that was particularly evident in the seed region, is probably due to the intense effects of purifying selection. Indeed, the importance of the miRNA seeds is revealed by the high conservation of their sequence across species [17,55,56], as this sequence ultimately determines the success of the miRNA-mRNA interactions [2]. In our study, a total of 221, 52 and 12 SNPs were found in precursor, mature and seed regions within miRNA loci, respectively ( Additional files 2 and 5: Table S2, Fig.…”
Section: Discussionmentioning
confidence: 82%
See 1 more Smart Citation
“…The low variability of miRNA genes, a feature that was particularly evident in the seed region, is probably due to the intense effects of purifying selection. Indeed, the importance of the miRNA seeds is revealed by the high conservation of their sequence across species [17,55,56], as this sequence ultimately determines the success of the miRNA-mRNA interactions [2]. In our study, a total of 221, 52 and 12 SNPs were found in precursor, mature and seed regions within miRNA loci, respectively ( Additional files 2 and 5: Table S2, Fig.…”
Section: Discussionmentioning
confidence: 82%
“…Besides, the conservation of the repertoire of mRNAs targeted by a given miRNA depends mostly on the age of the associated miRNA gene, with novel miRNAs acquiring targets more rapidly than ancient miRNAs [15]. Conserved sites are particularly enriched in the 5’end of 3’UTR [12], although selective pressure on miRNA binding sites is not uniform across miRNA genes [16].…”
Section: Introductionmentioning
confidence: 99%
“…The AGO targeting mechanism supports this relationship: hAgo2 creates a strong seed, which is generally sufficient for target recognition, and uses its central gate to discourage miRNA-target pairing between seed and supplementary regions. Thus, miRNA-recognition elements are short and well-defined, allowing each miRNA to regulate hundreds of targets, and enabling straightforward acquisition and loss of miRNA-recognition sites over evolutionary time (Nozawa, Fujimi et al 2016, Simkin, Geissler et al 2020.…”
Section: Discussionmentioning
confidence: 99%
“…However, these sites exhibit a negative selection over time that tempers miRNA binding efficacy. Unlike targets of broadly expressed miRNAs, co-expressed targets of miRNAs that exhibit tissue specific expression tend to evolve effectivity-reducing alterations in target sites(79), suggesting that the major role of miRNAs is to fine-tune gene expression rather than to significantly alter it(80). The continued coevolution of cell miRNAs and their target genes presents an internal arms race that ultimately reduces the impact of the majority of miRNA-mRNA interactions.…”
Section: Discussionmentioning
confidence: 99%