AUTHOR=Lyu Yang , Liufu Zhongqi , Xiao Juan , Tang Tian 

TITLE=A Rapid Evolving microRNA Cluster Rewires Its Target Regulatory Networks in Drosophila

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.760530

DOI=10.3389/fgene.2021.760530

ISSN=1664-8021

ABSTRACT=<p>New miRNAs are evolutionarily important but their functional evolution remains unclear. Here we report that the evolution of a microRNA cluster, <italic>mir-972C</italic> rewires its downstream regulatory networks in <italic>Drosophila</italic>. Genomic analysis reveals that <italic>mir-972C</italic> originated in the common ancestor of <italic>Drosophila</italic> where it comprises six old miRNAs. It has subsequently recruited six new members in the <italic>melanogaster</italic> subgroup after evolving for at least 50 million years. Both the young and the old <italic>mir-972C</italic> members evolved rapidly in seed and non-seed regions. Combining target prediction and cell transfection experiments, we found that the seed and non-seed changes in individual <italic>mir-972C</italic> members cause extensive target divergence among <italic>D. melanogaster</italic>, <italic>D. simulans</italic>, and <italic>D. virilis</italic>, consistent with the functional evolution of <italic>mir-972C</italic> reported recently. Intriguingly, the target pool of the cluster as a whole remains relatively conserved. Our results suggest that clustering of young and old miRNAs broadens the target repertoires by acquiring new targets without losing many old ones. This may facilitate the establishment of new miRNAs in existing regulatory networks.</p>