The expansion of the metazoan microRNA repertoire.
BACKGROUND
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.


RESULTS
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.


CONCLUSIONS
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.
Bioinformatics Group, Department of Computer Science, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany. jana@bioinf.uni-leipzig.de
Jana
J
Hertel
Manuela
M
Lindemeyer
Kristin
K
Missal
Claudia
C
Fried
Andrea
A
Tanzer
Christoph
C
Flamm
Ivo L
IL
Hofacker
Peter F
PF
Stadler
D000818:Animals; D001483:Base Sequence; D016000:Cluster Analysis; D004247:DNA / Q000737:chemistry; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D008322:Mammals / Q000235:genetics; D035683:MicroRNAs / Q000737:chemistry / Q000145:classification* / Q000235:genetics*; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D012091:Repetitive Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014404:Tubulin / Q000235:genetics; D014714:Vertebrates / Q000235:genetics
D035683:MicroRNAs; D014404:Tubulin; D004247:DNA