The expansion of the metazoan microRNA repertoire

We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozen ancient microRNA clusters.Our results suggest that microRNA innovation is an ongoing process. Major expansions of the metazoan miRNA repertoire coincide with the advent of bilaterians, vertebrates, and (placental) mammals.MicroRNAs (miRNAs) are small non-coding RNAs that can be found in both multi-cellular animals and plants. In both kingdoms they act as negative regulators of translation. They are transcribed as longer primary transcripts from which approximately 70nt precursors (pre-miRNAs) with a characteristic stem-loop structure are extracted; after export to the cytoplasm, the mature miRNAs, approximately 22nt in length, are cut out from one side of the precursor stem structure. For reviews on the discovery and function of miRNAs we refer to the literature, see e.g. [1,2].Despite the rapid growth of our knowledge on microRNA regulation, little is known about the evolution and phylogenetic distribution of the hundreds of animal microRNA families. The exceptions are a few well-studied examples, including let-7 [3-5], the three non-homologous miRNA families comprising the mir-17 cluster [6,7], two Hox-cluster associated genes mir-10 and mir-196 [8,9], and the exceptional imprinted mir-134 cluster of microRNAs located at human locus 14q32 [10-12]. These few case studies, which were sel