Human microRNAs preferentially target genes with intermediate levels of expression and its formation by mammalian evolution

MicroRNAs (miRNAs) are short, endogenous RNAs that post-transcriptionally repress mRNAs. Over the course of evolution, many new miRNAs are known to have emerged and added to the existing miRNA repertoires of drosophilids and vertebrates. Despite the large number of miRNAs in existence, the complementary pairing of only ~7 bases between miRNAs and mRNAs is sufficient to induce repression. Thus, miRNA targeting is so widespread that genes coexpressed with a miRNA have evolved to avoid sites that are targeted by the miRNA. Besides this avoidance, little is known about the preferential modes of miRNA targeting. Therefore, to elucidate miRNA targeting preference and avoidance, we evaluated the bias of the number of miRNA targeting occurrences in relation to expression intensities of miRNAs and their coexpressed target mRNAs by surveying transcriptome data from human organs. We found that miRNAs preferentially target genes with intermediate levels of expression, while avoiding highly expressed ones, and that older miRNAs have greater targeting specificity, suggesting that specificity increases during the course of evolution.