The evolution of gene regulation by transcription factors and microRNAs

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Abstract
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.