Gene by Environment Interactions reveal new regulatory aspects of signaling network plasticity

Abstract

Phenotypes can change during exposure to different environments through the regulation of signaling pathways that operate in integrated networks. How signaling networks produce different phenotypes in different settings is not fully understood. Here, Gene by Environment Interactions (GEIs) were used to explore the regulatory network that controls filamentous/invasive growth in the yeast Saccharomyces cerevisiae. GEI analysis revealed that the regulation of invasive growth is decentralized and varies extensively across environments. Different regulatory pathways were critical or dispensable depending on the environment, microenvironment, or time point tested, and the pathway that made the strongest contribution changed depending on the environment. Some regulators even showed conditional role reversals. Ranking pathways’ roles across environments revealed an under-appreciated pathway (OPI1) as the single strongest regulator among the major pathways tested (RAS, RIM101, and MAPK). One mechanism that may explain the high degree of regulatory plasticity observed was conditional pathway interactions, such as conditional redundancy and conditional cross-pathway regulation. Another mechanism was that different pathways conditionally and differentially regulated gene expression, such as target genes that control separate cell adhesion mechanisms (FLO11 and SFG1). An exception to decentralized regulation of invasive growth was that morphogenetic changes (cell elongation and budding pattern) were primarily regulated by one pathway (MAPK). GEI analysis also uncovered a round-cell invasion phenotype. Our work suggests that GEI analysis is a simple and powerful approach to define the regulatory basis of complex phenotypes and may be applicable to many systems.

PKA regulatory subunit Bcy1 couples growth, lipid metabolism, and fermentation during anaerobic xylose growth in Saccharomyces cerevisiae

“…Finally, re-evolving a coupling between anaerobic-xylose growth and metabolism in the bcy1Δ parent implicated mutations in PKA subunit TPK1 and the Ino2/4 repressor OPI1 (Table 2), which is known to be directly regulated by PKA phosphorylation [48]. Opi1 has complex roles in regulating phospholipids, including during the switch to invasive growth depending on nutrients [80], a process also regulated by the RAS/PKA pathway [81][82][83][84][85]. While we were unable to elucidate the exact role of these alleles, our results suggest that the OPI1 mutation may alter Opi1 regulation, especially given that the identified mutation in Opi1 occurs at a known CKII kinase site that regulates Opi1 activity [57].…”

PKA regulatory subunit Bcy1 couples growth, lipid metabolism, and fermentation during anaerobic xylose growth inSaccharomyces cerevisiae

“…Finally, re-evolving a coupling between anaerobic-xylose growth and metabolism in the bcy1∆ parent implicated mutations in PKA subunit TPK1 and the Ino2/4 repressor OPI1 (Table 2), which is known to be directly regulated by PKA phosphorylation (64). Opi1 has complex roles in regulating phospholipids, including during the switch to invasive growth depending on nutrients (90), a process also regulated by the RAS/PKA pathway (91)(92)(93)(94)(95). While we were unable to elucidate the exact role of these alleles, our results suggest that the OPI1 mutation may alter Opi1 regulation, especially given that the identified mutation in Opi1 occurs at a known CKII kinase site and is implicated in activating Opi1 (73).…”

Evaluation of grain yield performance and its stability in various spring barley accessions under condition of different agroclimatic zones of Ukraine

“…Thus, the phenotype formation is associated with the complex interaction of various systems and pathways of the organism (genotype) in response to the pressure (magnitude, duration, etc.) of different environmental factors (King, 2015;Li et al, 2018;Cammarano et al, 2021;Vandermeulen & Cullen, 2022). As a result, the genotype by environment interaction is quite difficult to study.…”