Conservation and evolvability in regulatory networks: The evolution of ribosomal regulation in yeast

Abstract

Transcriptional modules of coregulated genes play a key role in regulatory networks. Comparative studies show that modules of coexpressed genes are conserved across taxa. However, little is known about the mechanisms underlying the evolution of module regulation. Here, we explore the evolution of cis-regulatory programs associated with conserved modules by integrating expression profiles for two yeast species and sequence data for a total of 17 fungal genomes. We show that although the cis-elements accompanying certain conserved modules are strictly conserved, those of other conserved modules are remarkably diverged. In particular, we infer the evolutionary history of the regulatory program governing ribosomal modules. We show how a ciselement emerged concurrently in dozens of promoters of ribosomal protein genes, followed by the loss of a more ancient cis-element. We suggest that this formation of an intermediate redundant regulatory program allows conserved transcriptional modules to gradually switch from one regulatory mechanism to another while maintaining their functionality. Our work provides a general framework for the study of the dynamics of promoter evolution at the level of transcriptional modules and may help in understanding the evolvability and increased redundancy of transcriptional regulation in higher organisms.regulatory motifs ͉ transcriptional networks T ranscriptional modules, i.e., groups of coregulated genes, play a central role in the organization and function of regulatory networks (1-3). Comparative studies have demonstrated that various transcriptional modules are highly conserved across a wide variety of organisms from Escherichia coli to humans (4-6). A common tacit assumption is that conserved regulatory mechanisms underlie module conservation, because coregulation imposes tight constraints on the evolution of a module's promoters. Indeed, recent studies showed that orthologous transcriptional modules are often associated with conserved cis-elements (7).To gain new insights into the evolution of regulation of transcriptional modules, we developed an integrated method for comparative expression and sequence analysis. We applied our method to 17 fully sequenced yeast genomes and identified conserved transcriptional modules and the cis-elements that are associated with them in each species. Although the cis-elements associated with certain modules were conserved in all species, other modules were associated with distinct cis-elements in different species. Divergence of cis-elements in specific promoters has been documented, e.g., in refs. 8 and 9, but it is difficult to explain in a similar way the divergence we observed in a regulatory program associated with dozens of coexpressed genes. In particular, it is not clear how multiple promoters diverge in a coordinated way and how divergence occurs without adversely affecting the coexpression phenotype. To answer this question, we inferred the detailed evolutionary history of modules' regulatory programs and studied different evolutionary...

Growth rate controls mRNA turnover in steady and non-steady states

“…S1) versus their median transcription rate (TR, A-B), total [mRNA] (RA, C-D) and the degradation rate constant (k d , E-F) of their transcriptomes (see 15 other stresses show a positive correlation between TR and GR ( Fig. 2A), rather like that observed under steady-state conditions (see 18 ). On the contrary, the k d profiles show a positive correlation with iGR in all the stress responses ( Fig.…”

“…8 This regulatory behavior of respiration-related genes is specific for Crabtree-positive yeasts, 17 such as S. cerevisiae, because of the specialized evolved physiology of these organisms. 16,18 It is noteworthy that the way to achieve the correlation with GR differs. On the one hand, the ribosome-related and ESR-up genes vary their mRNA levels by changing their synthesis rates.…”

Rearrangements of the transcriptional regulatory networks of metabolic pathways in fungi

“…Early evidence for changes in gene regulation among fungi came from transcriptional profiling studies comparing S. cerevisiae, S. pombe and C. albicans [13][14][15]. Furthermore, predictions of cis-regulatory sequences, and meta-analyses of gene co-expression revealed that transcription networks have a great deal of flexibility [4,[16][17][18]. A well characterized example of comparative genomics applied to gene expression evolution is mating type identity that is controlled by distinct circuits with identical logic in S. cerevisiae and C. albicans [19 ].…”

Influence of Promoter Length on Network Convergence in GRN-Based Evolutionary Algorithms

“…More precisely, the goal is to understand which GRN properties improve the evolvability of living organisms. Some properties have already been highlighted in several articles [11][12][13]. Algorithms have been created to take advantage of them as Artificial Ontogeny [14] or lately PBGA [15].…”