Like protein-coding genes, loci that produce microRNAs (miRNAs) are generally considered to be under purifying selection [], consistent with miRNA polymorphisms being able to cause disease []. Nevertheless, it has been hypothesized that variation in miRNA genes may contribute to phenotypic diversity []. Here we demonstrate that a naturally occurring polymorphism in the MIR164A gene affects leaf shape and shoot architecture in Arabidopsis thaliana, with the effects being modified by additional loci in the genome. A single base pair substitution in the miRNA complementary sequence alters the predicted stability of the miRNA:miRNA∗ duplex. It thereby greatly reduces miRNA accumulation, probably because it interferes with precursor processing. We demonstrate that this is not a rare exception and that natural strains of Arabidopsis thaliana harbor dozens of similar polymorphisms that affect processing of a wide range of miRNA precursors. Our results suggest that natural variation in miRNA biogenesis resulting from cis mutations is a common contributor to phenotypic variation in plants.

DOI: 10.1016/j.cub.2011.11.060
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