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Project Progress

The Peterson lab has continued its focus on microRNAs (miRNA). Because of their importance as gene regulators during animal development, and their relevance in human diseases like cancer, to say nothing of potentially being drivers of morphological complexity, miRNA are among the most intensively studied and discussed molecules of the last 20 years. Although much is known about miRNA procession and structural restraints, their small size (~22 nt), the fact that they are non-coding, and the diversity of miRNA prediction software, determining what is and what is not a miRNA is not straight forward. An understanding of the evolution of miRNAs can only be achieved though if the number of false-positives is virtually zero, and if a common nomenclature—a catalogue of homologous microRNA genes of relevant organisms—is in place. Here we present a uniform system for the annotation and nomenclature of miRNA genes that we apply to the human miRNA entries in miRBase. We show that less than a third of these entries can be supported as derived from canonical miRNA genes, and that the evolutionary history of these miRNA genes was shaped in particular by periods of intense miRNA innovation, periods of evolution not intimately associated with genome duplication events. Further, we show that the mature miRNA gene products have a very different tempo and mode of sequence evolution as compared to the star products, differences related to interactions between mature miRNAs and target mRNAs as well as the star arm and the processing machinery. We establish a new open-access database—MirGeneDB.org (see Fig. 1)—to catalogue this bona fide set of human miRNAs that complements the efforts of miRBase, but differs from it in several fundamental ways including the annotation of mature versus star products, and the imposition of a taxonomic hierarchy upon this curated and consistently-named repertoire.