Coding Genes Helped the Origination and Diversification of Intragenic MicroRNAs

Noncoding microRNAs tend to evolve within introns of coding genes that provide them with transcriptional opportunity. As an outcome of natural selection, the intragenic position of microRNAs is crucial for their expression, evolution, and functional cooperation with the host gene. Therefore, understanding the evolution of intragenic microRNA structures may bring novel insights into genetic and phenotypic evolution. However, it remains largely unexplored. Here, by analyzing microRNA genomics in 34 metazoan species, we found that the majority (630/1,154) of microRNA families originated from introns of coding genes that provided them with initial transcriptional capacity. The most rapid expansion of intragenic microRNAs happened at the advent of vertebrates when 21 microRNA families emerged from introns of neural genes and reorganized the gene regulatory network, leading to the rise of vertebrate-specific neural crest cells, which transformed the invertebrate head and enabled the ecological shift from filter feeding to active predation. Intragenic microRNAs gradually gain independence from their host genes, which is accelerated by whole-genome duplications. After a whole-genome duplication, the purging of redundant host genes often set an orphaned microRNA "free" to diversify with the transcriptional elements inherited from the host. Whole-genome duplications facilitated a dramatic microRNA diversification during the initial divergence of vertebrates, as the intragenic status of 12 neural crest-regulating microRNAs was retained in jawed vertebrates but was lost in jawless cyclostomes, which diverged their neural crest development. We propose that coding genes not only facilitate the origination of new microRNAs, but also "sacrifice" themselves to help microRNA diversification.