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,wefocusedonthreeDrosophilamiRNAs withdifferent ages.As a result,we foundthat anoldermiRNAhas agreater number of target genes than a younger miRNA, suggesting the increasing number of targets for each miRNA during evolution (increasingmodel).Tofurtherconfirmour results,we alsopredicted all targetgenes for allmiRNAsinD.melanogaster, considering coexpressionofmiRNAsandmRNAs in vivo. Theresultsobtainedalsodonot support thedecreasingmodelbut 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 decreasingmodel of miRNA-target pairs should be reconsidered and the increasingmodelmay bemore appropriate to explain the evolutionary transitions of miRNA-target pairs in many organisms.