Microevolution of Nematode miRNAs Reveals Diverse Modes of Selection.

Micro-RNA (miRNA) genes encode abundant small regulatory RNAs that play key roles during development and in homeostasis by fine tuning and buffering gene expression. This layer of regulatory control over transcriptional networks is preserved by selection across deep evolutionary time, yet selection pressures on individual miRNA genes in contemporary populations remain poorly characterized in any organism. Here, we quantify nucleotide variability for 129 miRNAs in the genome of the nematode Caenorhabditis remanei tounderstandthemicroevolutionof this important classof regulatorygenes. Our analysis of threepopulation samples and C. remanei's sister species revealed ongoing natural selection that constrains evolution of all sequence domains within miRNA hairpins. We also show that new miRNAs evolve faster than older miRNAs but that selection nevertheless favors their persistence. Despite the ongoing importance of purging of new mutations, we discover a trove of >400 natural miRNA sequence variants that include single nucleotide polymorphisms in seed motifs, indels that ablatemiRNAfunctional domains, and origination of new miRNAs by duplication. Moreover, we demonstrate substantial nucleotide divergence of pre-miRNA hairpin alleles between populations andsister species. These findings from the first global survey ofmiRNAmicroevolution in Caenorhabditis support the idea that changes in gene expression, mediated through divergence in miRNA regulation, can contribute to phenotypic novelty and adaptation to specific environments in the present day as well as the distant past. [ABSTRACT FROM AUTHOR]