MicroRNAs (miRNAs) have ancient origins and were present as gene regulators early on in the evolution of animals.
The number of miRNA genes correlates with organismal complexity. Several waves of miRNA innovation have occurred: at the base of bilaterian lineage (the bilaterian expansion), at the base of the vertebrate lineage and in placental mammals.
miRNA genes evolve relatively easily, compared to protein-coding genes, from various genomic sources, including gene duplications, introns, pseudogenes, transposable elements, antisense transcripts and intergenic regions (de novo emergence).
Diversification of miRNA genes can take place by various mechanisms, including direct nucleotide changes in the seed region, seed shifting, arm switching and hairpin shifting.
miRNA targets can be easily acquired and lost.
The expression patterns of conserved miRNAs are overall conserved over large evolutionary distances. However, orthologous miRNAs in closely related species can vary in their spatio-temporal expression patterns.
miRNAs confer robustness to gene networks and provide reduction in variability of traits (canalization). The canalization of traits is an important mechanism in the evolution of increasing morphological complexity.
In the past decade, microRNAs (miRNAs) have been uncovered as key regulators of gene expression at the post-transcriptional level. The ancient origin of miRNAs, their dramatic expansion in bilaterian animals and their function in providing robustness to transcriptional programmes suggest that miRNAs are instrumental in the evolution of organismal complexity. Advances in understanding miRNA biology, combined with the increasing availability of diverse sequenced genomes, have begun to reveal the molecular mechanisms that underlie the evolution of miRNAs and their targets. Insights are also emerging into how the evolution of miRNA-containing regulatory networks has contributed to organismal complexity.
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The author would like to thank K. J. Peterson and the anonymous referees for their insightful comments on the manuscript and members of his laboratory for stimulating discussions. The author is a European Molecular Biology Organisation (EMBO) Young Investigator. This work is supported by a VIDI grant from The Netherlands Organisation for Scientific Research (NWO).
Eugene Berezikov is a co-founder of InetRNA Technologies B.V. and a InteRNA Genomics B.V.
The homology between two genomic segments in the same organism that arose from a duplication event.
The division of the ancestral function of a gene following gene duplication, in which different copies of the duplicated gene retain different aspects of the original function.
The acquisition of a novel function by one of the copies of a duplicated gene, which comes about through mutational changes.
- DNA transposons
Transposable elements that rely on a transposase enzyme to excise themselves from one region of the genome and insert themselves into a different region without increasing in copy number.
Transposable element that replicates via an RNA intermediate, which is converted by reverse transcriptase to cDNA. The cDNA can be inserted into genomic DNA, increasing the number of copies of the retrotransposon in the genome.
- PIWI-interacting RNAs
(piRNAs). Single-stranded RNAs in the range of 25–35 nucleotides that form complexes with the PIWI protein. piRNAs are involved in transposon silencing.
One of the strands in the imperfect double-stranded intermediate RNA duplex that is generated after processing of the primary miRNA precursor RNA by Drosha and Dicer. The other strand — mature miRNA — is predominantly loaded into the miRNA-induced silencing complex (miRISC), whereas miRNA* is degraded.
Random fluctuations in allele frequencies as genes are transmitted from one generation to the next.
- Coherent feedforward loop
A gene network motif in which a regulator gene controls a target gene directly, as well as indirectly, through another regulator, and both regulation paths act in the same direction on the target.
- Incoherent feedforward loop
A gene network motif where a regulator gene controls the target gene directly as well as indirectly through another regulator, and the two regulation paths act in opposite directions on the target.
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Berezikov, E. Evolution of microRNA diversity and regulation in animals. Nat Rev Genet 12, 846–860 (2011). https://doi.org/10.1038/nrg3079
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