The deep evolution of metazoan microRNAs

Abstract

microRNAs (miRNAs) are approximately 22-nucleotide noncoding RNA regulatory genes that are key players in cellular differentiation and homeostasis. They might also play important roles in shaping metazoan macroevolution. Previous studies have shown that miRNAs are continuously being added to metazoan genomes through time, and, once integrated into gene regulatory networks, show only rare mutations within the primary sequence of the mature gene product and are only rarely secondarily lost. However, because the conclusions from these studies were largely based on phylogenetic conservation of miRNAs between model systems like Drosophila and the taxon of interest, it was unclear if these trends would describe most miRNAs in most metazoan taxa. Here, we describe the shared complement of miRNAs among 18 animal species using a combination of 454 sequencing of small RNA libraries with genomic searches. We show that the evolutionary trends elucidated from the model systems are generally true for all miRNA families and metazoan taxa explored: the continuous addition of miRNA families with only rare substitutions to the mature sequence, and only rare instances of secondary loss. Despite this conservation, we document evolutionary stable shifts to the determination of position 1 of the mature sequence, a phenomenon we call seed shifting, as well as the ability to post-transcriptionally edit the 5' end of the mature read, changing the identity of the seed sequence and possibly the repertoire of downstream targets. Finally, we describe a novel type of miRNA in demosponges that, although shows a different pre-miRNA structure, still shows remarkable conservation of the mature sequence in the two sponge species analyzed. We propose that miRNAs might be excellent phylogenetic markers, and suggest that the advent of morphological complexity might have its roots in miRNA innovation.

Systematic analysis of human microRNA divergence based on evolutionary emergence

“…Moreover, we also observed that a small fraction of novel miRNA emerged at different time points are copies of members of ancestral families except for metazoan and human-specific. The emergence of these new miRNA genes which are copies of members of ancestral families could be due to genome duplication events (GDEs), including the occurrence of tandem duplications and non-local duplications, which increased diversity of miRNA genes [22]. Further analysis revealed that a large portion of novel human miRNA genes emerged at different time points are copies of new families, suggesting that novel miRNA genes often experience genome duplication events.…”

Evolution of the Mir-155 Family and Possible Targets in Cancers and the Immune System

“…The evolutionary process of microRNA is slower even than the most conserved genes in the metazoan genome (GrimsonSrivastava et al, 2008;Wheeler et al, 2009). Therefore, it is possible for microRNA families to be used in tracking the evolutionary origin of the most ancient animal phylogeny.…”

Diversity, evolution, and therapeutic applications of small RNAs in prokaryotic and eukaryotic immune systems

“…Other ways that new miRNAs can arise include the modification or duplication of pre-existing miRNAs [108]. A rapid increase in the diversity of miRNAs in existing genomes is often correlated to a burst of new morphological diversity, and thus miRNA may be crucial to the development of complex morphologies because of its regulatory activity [71,110,134].…”

“…Once an miRNA has gained a function, it rarely is lost from the genome [108,110]. Because older miRNAs evolve at a very low rate, and as a result are well conserved, they can be used as excellent phylogenetic markers [134].…”