Journal
JOURNAL OF MOLECULAR EVOLUTION
Volume 63, Issue 2, Pages 174-182Publisher
SPRINGER
DOI: 10.1007/s00239-005-0273-2
Keywords
coding sequence evolution; mammals; microRNA-mediated regulation; pairing domains; positive selection; synonymous mutations
Funding
- MRC [G0300415] Funding Source: UKRI
- Medical Research Council [G0300415] Funding Source: researchfish
- Medical Research Council [G0300415] Funding Source: Medline
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Despite prior claims to the contrary, several lines of evidence suggest that selection acts on synonymous mutations in mammals. What might be the mechanisms for such selection? Here I attempt to quantify the constraints on the evolution of the coding sequence resulting from regulation of mRNA by microRNAs (miRNAs) that antisense-bind to the coding region of mRNAs. I employ a set of genes recently experimentally verified to be the target of a miRNA, all with putative antisense pairing domains within the coding sequence. Although very small (similar to 22 nucleotides), 2 of 13 pairing domains show evidence of significantly slow sequence evolution. This, along with evidence that these genes are regulated by the miRNA under consideration, provides the first good candidate domains for intra-CDS pairing of a miRNA in mammals. When analyzed en masse, the putative pairing domains have a significantly reduced rate of synonymous evolution (similar to 35% lower than null). However, given the size and rarity of pairing domains within the coding sequence, the effects that such constraint has on estimates of the mutation rate are small enough to be ignored (probably less than 1% reduction). The pairing sites also have low K-a values and the selection on the synonymous sites is unlikely to lead to misleading reports of localized high K-a/K-s ratios.
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