Abstract
MicroRNA play an important role in post-transcriptional regulation of most transcripts in the human genome, but their evolution across the primate lineage is largely uncharacterized. A particular miRNA can have one to thousands of messenger RNA targets, establishing the potential for a small change in sequence or overall miRNA structure to have profound phenotypic effects. However, the majority of non-human primate miRNA is predicted solely by homology to the human genome and lacks experimental validation. In the present study, we sequenced thirteen species representing a wide range of the primate phylogeny. Hundreds of miRNA were validated, and the number of species with experimentally validated miRNA was tripled. These species include a sister taxon to humans (bonobo) and basal primates (aye-aye, mouse lemur, galago). Consistent with previous studies, we found the seed region and mature miRNA to be highly conserved across primates, with overall structural conservation of the pre-miRNA hairpin. However, there were a number of interesting exceptions, including a seed shift due to structural changes in miR-501. We also identified an increase in the number of miR-320 paralogs throughout primate evolution. Many of these non-conserved miRNA appear to regulate neuronal processes, illustrating the importance of investigating miRNA to learn more about human evolution.
Highlights
Comparative genomics is an indispensable tool for studying the evolutionary history of any organism
Our understanding of functional genomics has been facilitated by technological advances in high throughput transcriptomic and proteomic methods
These tools are rapidly expanding our understanding of miRNA, a relatively new class of trans-acting regulators of gene expression that are quickly being recognized as potential sources of phenotypic variation or as biomarkers for disease
Summary
Comparative genomics is an indispensable tool for studying the evolutionary history of any organism. Studies comparing protein coding sequence data has uncovered rapid evolution between primates in many key areas, including immunity, sensory perception, reproduction, and keratinization [1, 2, 3]. Results from genomic scale analyses continue to reinforce that much, if not most, phenotypic differences between species result from changes in gene expression and not amino acid divergence [3, 4, 5, 6, 7]. While there are many layers of gene regulation that exist between DNA sequence data and expressed proteins, emphasis is often placed on the mechanisms that regulate transcription. There has been much work characterizing the coevolution of transcription factors and their DNA binding elements [8]. In addition to RNA binding proteins, microRNAs (miRNA) are an important class of post-transcriptional trans-acting factors that regulate mRNA stability
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