Abstract

BackgroundMicroRNAs (miRNAs) are negative regulators of gene expression in multicellular eukaryotes. With the recently completed sequencing of three primate genomes, the study of miRNA evolution within the primate lineage has only begun and may be expected to provide the genetic and molecular explanations for many phenotypic differences between human and non-human primates.FindingsWe scanned all three genomes of non-human primates, including chimpanzee (Pan troglodytes), orangutan (Pongo pygmaeus), and rhesus monkey (Macaca mulatta), for homologs of human miRNA genes. Besides sequence homology analysis, our comparative method relies on various postprocessing filters to verify other features of miRNAs, including, in particular, their precursor structure or their occurrence (prediction) in other primate genomes. Our study allows direct comparisons between the different species in terms of their miRNA repertoire, their evolutionary distance to human, the effects of filters, as well as the identification of common and species-specific miRNAs in the primate lineage. More than 500 novel putative miRNA genes have been discovered in orangutan that show at least 85 percent identity in precursor sequence. Only about 40 percent are found to be 100 percent identical with their human ortholog.ConclusionHomologs of human precursor miRNAs with perfect or near-perfect sequence identity may be considered to be likely functional in other primates. The computational identification of homologs with less similar sequence, instead, requires further evidence to be provided.

Highlights

  • IntroductionMicroRNAs (miRNAs) are negative regulators of gene expression in multicellular eukaryotes

  • MicroRNAs are negative regulators of gene expression in multicellular eukaryotes

  • MicroRNAs constitute a class of short endogenous non-coding RNA sequences which directly function as negative regulators of gene expression at the post-transcriptional level in multicellular eukaryotes

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Summary

Introduction

MicroRNAs (miRNAs) are negative regulators of gene expression in multicellular eukaryotes. MicroRNAs (miRNAs) constitute a class of short endogenous non-coding RNA (ncRNA) sequences which directly function as negative regulators of gene expression at the post-transcriptional level in multicellular eukaryotes The ~70 nt long precursor of animal miRNAs (pre-miRNA) forms a typical hairpin-like stem-loop structure. The contained mature miRNA is only ~22 nt long and binds to complementary target sites in the untranslated region (UTR) of messenger RNA. Perfect base-pairing is found only for a 6-8 nt long seed region located at the 5’ end of the miRNA. One miRNA may at least theoretically target hundreds of genes. Comparative approaches to discover miRNA genes [4,5] rely on sequence homology to known miRNAs [6], sequence profiles [7], characteristic secondary structure

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