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The evolution of gene regulation by transcription factors and microRNAs

Nature Reviews Genetics volume 8, pages 93–103 (2007)Cite this article

Key Points

  • Gene regulation in multicellular eukaryotes is complex, with many layers of regulation. Two fundamental mechanisms of gene regulation involve transcription factors and microRNAs, a large class of small, non-coding RNAs.

  • It is widely believed that phenotypic evolution is closely linked to the evolution of gene regulation. To begin to understand the evolution of gene regulatory networks, it is important to first understand how the individual regulators and their regulatory interactions evolve.

  • A combination of computational and experimental work has made it possible to begin to compare the evolution of transcriptional regulation with post-transcriptional regulation that is carried out by microRNAs.

  • For both transcription factors and microRNAs, the regulators themselves seem to be well conserved over large evolutionary distances, whereas their targets seem to have evolved much more quickly, indicating that large-scale rewiring of regulatory networks has taken place in the course of evolution.

  • In animal evolution, the acquisition of new microRNA families seems to have been much more rapid than the acquisition of new transcription-factor families. Several authors have proposed that new microRNA families have had important roles in the development of novel tissue types and organs.

  • Ultimately, a comprehensive picture of gene-regulation evolution will require a unification of different regulatory mechanisms. As an initial step in this direction, we suggest a simple model that describes the transcription of new microRNA genes. A corollary of this model is that many microRNAs that are expressed at low levels and in specific spatio-temporal domains might have little biological function in regulating target genes in trans.

Abstract

Changes in the patterns of gene expression are widely believed to underlie many of the phenotypic differences within and between species. Although much emphasis has been placed on changes in transcriptional regulation, gene expression is regulated at many levels, all of which must ultimately be studied together to obtain a complete picture of the evolution of gene expression. Here we compare the evolution of transcriptional regulation and post-transcriptional regulation that is mediated by microRNAs, a large class of small, non-coding RNAs in plants and animals, focusing on the evolution of the individual regulators and their binding sites. As an initial step towards integrating these mechanisms into a unified framework, we propose a simple model that describes the transcriptional regulation of new microRNA genes.

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Figure 1: Gene regulation by transcription factors and microRNAs.
Figure 2: A model of the acquisition of a new microRNA.

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Acknowledgements

We regret that due to space constraints, we are unable to cite the work of many colleagues who have made key contributions to the field. We thank K. Birnbaum for insightful discussions about gene regulation in plants, and V. Ambros, M. Hammell, S. Small and N. Sokol for helpful comments on a preliminary version of the manuscript.

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Authors and Affiliations

  1. Department of Biology, Center for Comparative Functional Genomics, New York University, New York, 10003, New York, USA

    Kevin Chen & Nikolaus Rajewsky

  2. Max Delbrück Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, Berlin-Buch, 13125, Germany

    Nikolaus Rajewsky

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  1. Kevin Chen
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Correspondence to Nikolaus Rajewsky.

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Glossary

Bilaterians

Members of the animal kingdom that have bilateral symmetry — the property of having two similar sides, with definite upper and lower surfaces, and anterior and posterior ends.

Acoel flatworms

A basal bilaterian clade that diverged from the rest of bilaterians before the split between protostomes and deuterostomes.

Synteny

Collinearity in the order of genes or other DNA sequences in chromosomal regions of two species or in the same species.

Clade

A group of organisms that includes a common ancestor and all of its descendants, representing a distinct branch on a phylogenetic tree.

Cnidarians

Radially symmetrical animals that have sac-like bodies with only one opening. They include jellyfish, corals, hydra and anemones.

ChIP-chip analysis

A method that combines chromatin immunoprecipitation with microarray technology to identify in vivo targets of a transcription factor.

Deep sequencing

Sequencing to high coverage, where coverage (or depth) corresponds to the average number of times that a nucleotide is sequenced.

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Chen, K., Rajewsky, N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8, 93–103 (2007). https://doi.org/10.1038/nrg1990

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