Clusters of microRNAs emerge by new hairpins in existing transcripts
Antonio Marco, Maria Ninova, Matthew Ronshaugen, Sam Griffiths-Jones
(Submitted on 9 Apr 2013)

Genetic linkage may result in the expression of multiple products from a single polycistronic transcript, under the control of a single promoter. In animals, protein-coding polycistronic transcripts are rare. However, microRNAs are frequently clustered in the genomes of animals and plants, and these clusters are often transcribed as a single unit. The evolution of microRNA clusters has been the subject of much speculation, and a selective advantage of clusters of functionally related microRNAs is often proposed. However, the origin of microRNA clusters has not been so far systematically explored. Here we study the evolution of all microRNA clusters in Drosophila melanogaster, and suggest a number of models for their emergence. We observed that a majority of microRNA clusters arose by the de novo formation of new microRNA-like hairpins in existing microRNA transcripts. Some clusters also emerged by tandem duplication of a single microRNA. Comparative genomics show that these clusters, once formed, are unlikely to split or undergo rearrangements. We did not find any instances of clusters appearing by rearrangement of pre-existing microRNA genes. We propose a model for microRNA cluster origin and evolution in which selection over one of the microRNAs in the cluster interferes with the evolution of the other tightly linked microRNAs. Our analysis suggests that the evolutionary study of microRNAs and other small RNAs must consider and account for linkage associations.