Host gene constraints and genomic context impact the expression and evolution of human microRNAs.

Gustavo S França,Pedro A F Galante,Maria D Vibranovski

doi:10.1038/ncomms11438

Gustavo S França, Pedro A F Galante + Show 1 more

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https://doi.org/10.1038/ncomms11438

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Abstract

Increasing evidence has shown that recent miRNAs tend to emerge within coding genes. Here we conjecture that human miRNA evolution is tightly influenced by the genomic context, especially by host genes. Our findings show a preferential emergence of intragenic miRNAs within old genes. We found that miRNAs within old host genes are significantly more broadly expressed than those within young ones. Young miRNAs within old genes are more broadly expressed than their intergenic counterparts, suggesting that young miRNAs have an initial advantage by residing in old genes, and benefit from their hosts' expression control and from the exposure to diverse cellular contexts and target genes. Our results demonstrate that host genes may provide stronger expression constraints to intragenic miRNAs in the long run. We also report associated functional implications, highlighting the genomic context and host genes as driving factors for the expression and evolution of human miRNAs.

Highlights

Increasing evidence has shown that recent miRNAs tend to emerge within coding genes
Our analyses revealed that intragenic miRNAs are likely to emerge within old genes, pointing to important functional and evolutionary implications
We found that old host genes are more broadly expressed than young ones[22,23,32], having stronger signal of sequence constraint and are probably subjected to strong purifying selection, even when compared with old genes not harbouring miRNAs

Summary

Introduction

Increasing evidence has shown that recent miRNAs tend to emerge within coding genes. Here we conjecture that human miRNA evolution is tightly influenced by the genomic context, especially by host genes. We report associated functional implications, highlighting the genomic context and host genes as driving factors for the expression and evolution of human miRNAs. More than 20 years after microRNA (miRNA) discovery, followed by extensive research on its molecular characterization, we are currently aware of the broad impact of these small non-coding RNAs on the posttranscriptional regulation of gene expression. Given the functional importance and a suggestive selective advantage favouring such genomic organization, here we conjectured that the evolutionary context in which miRNAs emerge may be decisive to their expression and evolution It is well-recognized that old genes, compared with young ones, tend to evolve slowly, are more broadly expressed and subjected to strong purifying selection[21,22,23]. We discuss possible functional implications associated with miRNA evolution and their genomic location

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