This guest post is by Antonio Marco (@antonio_marco_c) on his paper Marco et al. Clusters of microRNAs emerge by new hairpins in existing transcripts arXived here.
MicroRNAs are short regulatory sequences involved in virtually all biological processes. MicroRNAs are often organized in genomic clusters that produce polycistronic transcripts. It is well-known that protein-coding polycistronic transcripts are almost absent in animals (with a few exceptions in nematodes and ascidians). So where do these microRNA clusters come from, and why are they so prevalent? We tackle these questions in our paper “Clusters of microRNAs emerge by new hairpins in existing transcripts”, recently deposited in arXiv.
We envisioned several possible scenarios for the origin of polycistronic microRNAs: First, polycistronic microRNAs can emerge by genomic rearrangements that bring together pre-existing microRNAs. As in bacterial operons, the clustering of microRNAs with related functions can be advantageous, and the fusion of related microRNAs may be positively selected. We call this the ‘put together’ model. Alternatively, multiple microRNAs could become polycistronic as a by-product of genome reduction (this is analogous to Caenorhabditis elegans operons). This is the ‘left together’ model. A third model, called ‘tandem duplication’, implies that polycistronic microRNAs emerge by tandem duplication of single sequences. Lastly, new microRNAs can emerge de novo in already existing microRNA transcripts. We named this the ‘new hairpin’ model, since a novel microRNA first requires the formation of a hairpin-like structure in the transcript.
By reconstructing the evolutionary history of Drosophila melanogaster microRNAs we observed that the majority of microRNA clusters emerged by the formation of new microRNA precursors in existing transcribed microRNA genes (‘new hairpin’ model). We also find that gene duplication generated a minority of the clusters (‘tandem duplication’). However, we didn’t see any instance of fusion of pre-existing microRNA genes. Moreover, clusters rarely split or suffer rearrangements. Once a microRNA cluster is formed, it stays as a cluster or it is lost a a whole.
We propose a model for the origin and evolution of microRNA clusters. Polycistronic microRNAs are an extreme case of genetic linkage, in which a microRNA is typically a few nucleotides away from another microRNA. Once a cluster is formed, the linkage is so tight that recombination is dramatically reduced between these loci. We suggest that, because of strong selective interference between loci (Hill-Robertson effect), a microRNA under selective pressure strongly influences the evolutionary fate of any neighbouring microRNA. Even slightly deleterious microRNAs may be maintained in a population if selection in one microRNA of the cluster is strong enough. Currently, we are analysing polymorphism data to test the validity of our model in actual Drosophila populations.
In summary, we suggest that clusters of microRNAs emerge by non-adaptive mechanisms and they are maintained as a consequence of tight linkage.