Coevolution within a transcriptional network by compensatory trans and cis mutations

Abstract

Transcriptional networks have been shown to evolve very rapidly, prompting questions as to how such changes arise and are tolerated. Recent comparisons of transcriptional networks across species have implicated variations in the cis-acting DNA sequences near genes as the main cause of divergence. What is less clear is how these changes interact with trans-acting changes occurring elsewhere in the genetic circuit. Here, we report the discovery of a system of compensatory trans and cis mutations in the yeast AP-1 transcriptional network that allows for conserved transcriptional regulation despite continued genetic change. We pinpoint a single species, the fungal pathogen Candida glabrata, in which a trans mutation has occurred very recently in a single AP-1 family member, distinguishing it from its Saccharomyces ortholog. Comparison of chromatin immunoprecipitation profiles between Candida and Saccharomyces shows that, despite their different DNA-binding domains, the AP-1 orthologs regulate a conserved block of genes. This conservation is enabled by concomitant changes in the cisregulatory motifs upstream of each gene. Thus, both trans and cis mutations have perturbed the yeast AP-1 regulatory system in such a way as to compensate for one another. This demonstrates an example of ''coevolution'' between a DNAbinding transcription factor and its cis-regulatory site, reminiscent of the coevolution of protein binding partners.

Cis- and trans-regulatory divergence between progenitor species determines gene-expression novelty in Arabidopsis allopolyploids

“…However, recent evidence indicates that gene-expression stability is maintained by coordinated cis-and trans-regulatory activities 17,18 . Changes in both cis-and transregulatory elements are responsible for the maintenance of the overall expression circuits 18 and coevolution between a DNA-binding transcription factor and its cis-binding site 19 .…”

Hybrid Incompatibility Despite Pleiotropic Constraint in a Sequence-Based Bioenergetic Model of Transcription Factor Binding

“…As with cis-regulatory regions, this modularity may allow tissue-specific or condition-specific evolutionary responses that affect only a subset of the TF's potential targets (Hsia and McGinnis 2003;Wagner and Lynch 2008). This inherent limit to the extent of pleiotropy is complemented by the possibility that pleiotropic changes occur but their deleterious effects are later compensated (Haag 2007;Kuo et al 2010;Pavlicev and Wagner 2012). Compensation can contribute to hybrid incompatibility if different combinations of deleterious and compensatory changes occur in diverging populations (Landry et al 2005).…”

Extensive DNA-binding specificity divergence of a conserved transcription regulator

“…These arguments include the amino acid conservation of transcription regulator DNA-binding domains (1), the potentially pleiotropic nature of alterations to transcription regulator DNAbinding specificity (2), and the conservation of function across large evolutionary distances for certain transcription regulators (3,4). Several cases of drift in the transcription regulator DNAbinding specificity have been documented across species, but the changes were limited to a small number of amino acid positions and the cis-regulatory sequence remained similar across species (5,6). Here, we show that the DNA-binding specificity of a deeply conserved transcription regulator (Matα1) can change so extensively that its cis-regulatory sequence in different species appears unrelated as assessed by bioinformatic criteria.…”