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Annu Rev Genet. 2015;49:213-42. doi: 10.1146/annurev-genet-120213-092023. Epub 2015 Oct 14.

A Uniform System for the Annotation of Vertebrate microRNA Genes and the Evolution of the Human microRNAome.

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Department of Tumor Biology, Institute for Cancer Research.
Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755; email:
Department of Biology and Health Sciences, New England College, Henniker, New Hampshire 03242.
Department of Biology, The National University of Ireland, Maynooth, Kildare, Ireland.
School of Earth Sciences, University of Bristol, BS8 1TQ Bristol, United Kingdom.
Kathryn W. Davis Center for Regenerative Biology and Medicine, Mount Desert Island Biological Laboratory, Salisbury Cove, Maine 04672.
Center for Cancer and Cell Biology, Van Andel Research Institute, Grand Rapids, Michigan 49503.
Department of Gastroenterological Surgery.
Institute of Clinical Medicine.
Institute of Cancer Genetics and Informatics, The Norwegian Radium Hospital, Oslo University Hospital, Nydalen, N-0424 Oslo, Norway.
Department of Informatics, University of Oslo, Blindern, N-0318 Oslo, Norway.


Although microRNAs (miRNAs) are among the most intensively studied molecules of the past 20 years, determining what is and what is not a miRNA has not been straightforward. Here, we present a uniform system for the annotation and nomenclature of miRNA genes. We show that less than a third of the 1,881 human miRBase entries, and only approximately 16% of the 7,095 metazoan miRBase entries, are robustly supported as miRNA genes. Furthermore, we show that the human repertoire of miRNAs has been shaped by periods of intense miRNA innovation and that mature gene products show a very different tempo and mode of sequence evolution than star products. We establish a new open access database--MirGeneDB ( )--to catalog this set of miRNAs, which complements the efforts of miRBase but differs from it by annotating the mature versus star products and by imposing an evolutionary hierarchy upon this curated and consistently named repertoire.


MirGeneDB; genome duplication; miRBase; miRNA; molecular evolution; vertebrate

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