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Preliminary Assessment of the Impact of MicroRNA-Mediated Regulation on Coding Sequence Evolution in Mammals

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Abstract

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 (∼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 (∼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 Ka values and the selection on the synonymous sites is unlikely to lead to misleading reports of localized high Ka/Ks ratios.

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Acknowledgements

The author would like to thank two anonymous reviewers for constructive comments.

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Authors and Affiliations

  1. Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, UK

    Laurence D. Hurst

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  1. Laurence D. Hurst
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Correspondence to Laurence D. Hurst.

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[Reviewing Editor: Dr. Manyuan Long]

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Hurst, L.D. Preliminary Assessment of the Impact of MicroRNA-Mediated Regulation on Coding Sequence Evolution in Mammals. J Mol Evol 63, 174–182 (2006). https://doi.org/10.1007/s00239-005-0273-2

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  • DOI: https://doi.org/10.1007/s00239-005-0273-2

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