title: Evolutionary Transitions of MicroRNA-Target Pairs.
abstract: How newly generated microRNA (miRNA) genes are integrated into gene regulatory networks during evolution is fundamental in understanding the molecular and evolutionary bases of robustness and plasticity in gene regulation. A recent model proposed that after the birth of a miRNA, the miRNA is generally integrated into the network by decreasing the number of target genes during evolution. However, this decreasing model remains to be carefully examined by considering in vivo conditions. In this study, we therefore compared the number of target genes among miRNAs with different ages, combining experiments with bioinformatics predictions. First, we focused on three Drosophila miRNAs with different ages. As a result, we found that an older miRNA has a greater number of target genes than a younger miRNA, suggesting the increasing number of targets for each miRNA during evolution (increasing model). To further confirm our results, we also predicted all target genes for all miRNAs in D. melanogaster, considering co-expression of miRNAs and mRNAs in vivo The results obtained also do not support the decreasing model but are reasonably consistent with the increasing model of miRNA-target pairs. Furthermore, our large-scale analyses of currently available experimental data of miRNA-target pairs also showed a weak but the same trend in humans. These results indicate that the current decreasing model of miRNA-target pairs should be reconsidered and the increasing model may be more appropriate to explain the evolutionary transitions of miRNA-target pairs in many organisms.
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan Department of Genetics, SOKENDAI, Shizuoka, Japan manozawa@tmu.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nozawa
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Fujimi
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Iwamoto
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Onizuka
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan.
authors.forename: Nana
authors.initials: N
authors.lastname: Fukuda
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan Department of Genetics, SOKENDAI, Shizuoka, Japan.
authors.forename: Kazuho
authors.initials: K
authors.lastname: Ikeo
authors.affiliation: Center for Information Biology, National Institute of Genetics, Shizuoka, Japan King Abdullah University of Science and Technology, Computational Bioscience Research Center, Biological and Environmental Science and Engineering, Thuwal, Kingdom of Saudi Arabia.
authors.forename: Takashi
authors.initials: T
authors.lastname: Gojobori
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D029721:Drosophila Proteins; C000614420:MIRN277 microRNA, Drosophila; C000614422:MIRN954 microRNA, Drosophila; C000614421:MIRN982 microRNA, Drosophila; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: RNA-seq; bioinformatics prediction; gene regulation; small RNA; transgenic fly