Origin and evolution of human microRNAs from transposable elements

We sought to evaluate the extent of the contribution of transposable elements (TEs) to human microRNA (miRNA) genes along with the evolutionary dynamics of TE-derived human miRNAs. We found 55 experimentally characterized human miRNA genes that are derived from TEs, and these TE-derived miRNAs have the potential to regulate thousands of human genes. Sequence comparisons revealed that TE-derived human miRNAs are less conserved, on average, than non-TE-derived miRNAs. However, there are 18 TE-derived miRNAs that are relatively conserved, and 14 of these are related to the ancient L2 and MIR families. Comparison of miRNA vs. mRNA expression patterns for TE-derived miRNAs and their putative target genes showed numerous cases of anti-correlated expression that are consistent with regulation via mRNA degradation. In addition to the known human miRNAs that we show to be derived from TE sequences, we predict an additional 85 novel TE-derived miRNA genes. TE sequences are typically disregarded in genomic surveys for miRNA genes and target sites; this is a mistake. Our results indicate that TEs provide a natural mechanism for the origination miRNAs that can contribute to regulatory divergence between species as well as a rich source for the discovery of as yet unknown miRNA genes.