Open Access Highly Accessed Research article

The expansion of the metazoan microRNA repertoire

Jana Hertel1, Manuela Lindemeyer1, Kristin Missal1, Claudia Fried1, Andrea Tanzer12, Christoph Flamm12, Ivo L Hofacker2, Peter F Stadler123* and The Students of Bioinformatics Computer Labs 2004 and 2005

Author Affiliations

1 Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany

2 Institute for Theoretical Chemistry, University of Vienna, Währingerstrasse 17, A-1090 Wien, Austria

3 The Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe NM 87501

For all author emails, please log on.

BMC Genomics 2006, 7:25  doi:10.1186/1471-2164-7-25

Published: 15 February 2006



MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript.


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.