Unicellular Origin of the Animal MicroRNA Machinery

The emergence of multicellular animals resulted in a jump in morphological complexity, with the acquisition of spatial cell differentiation, embryonic development, and high diversity of body plans. Paradoxically, this phenotypic transition is apparently not reflected as major changes in the underlying developmental gene pathways and regulatory networks. In fact, most of these systems are ancient and were invented already within the unicellular ancestors of animals1–5. In contrast, the Microprocessor protein machinery, which is essential for microRNA (miRNA) biogenesis in animals, as well as the miRNA genes themselves produced by this microprocessor, have not been identified outside of the animal kingdom. Here, we show using genomic and transcriptomic analyses that the unicellular sister lineages of animals, including Ichtyosporea, possess both Drosha and Pasha (DGCR8 in vertebrates), the components of the Microprocessor. This suggests that the Microprocessor complex evolved long before the last common ancestor of animals, consistent with a pre-metazoan origin of most of the animal developmental toolkit. By small RNA sequencing we also discovered expressed bona fide miRNA genes in several species of the ichthyosporean genus Sphaeroforma harboring the Microprocessor. A deep, pre-metazoan origin of the Microprocessor and miRNAs comply with a view that the origin of multicellular animals was not directly linked to the innovation of these key regulatory components.