Intersecting transcription networks constrain gene regulatory evolution

By Trevor R. Sorrells, Lauren N. Booth, Brian B. Tuch, Alexander Johnson. 2015

72 citations recorded by the source corpus.

Epistasis—the non-additive interactions between different genetic loci—constrains evolutionary pathways, blocking some and permitting others. For biological networks such as transcription circuits, the nature of these constraints and their consequences are largely unknown. Here we describe the evolutionary pathways of a transcription network that controls the response to mating pheromone in yeast. A component of this network, the transcription regulator Ste12, has evolved two different modes of binding to a set of its target genes. In one group of species, Ste12 binds to specific DNA binding sites, while in another lineage it occupies DNA indirectly, relying on a second transcription regulator to recognize DNA. We show, through the construction of various possible evolutionary intermediates, that evolution of the direct mode of DNA binding was not directly accessible to the ancestor. Instead, it was contingent on a lineage-specific change to an overlapping transcription network with a different function, the specification of cell type. These results show that analysing and predicting the evolution of cis-regulatory regions requires an understanding of their positions in overlapping networks, as this placement constrains the available evolutionary pathways.

Subfields: Molecular Biology

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Citations in the corpus

Evolution of resilience in protein interactomes across the tree of life (2018, background): “While studies based on sequence data alone have demonstrated evolution of genomes, mechanistic insights into how evolution shapes interactions between proteins in an organism remain elusive (9, 10).”