Integrated TORC1 and PKA signaling control the temporal activation of glucose-induced gene expression in yeast

Kunkel, Joseph G.; Luo, Xiangxia; Capaldi, Andrew P.

doi:10.1038/s41467-019-11540-y

Cited by 62 publications

(92 citation statements)

References 53 publications

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“…However, the tor1 mutant is more likely to acquire adaptive mutations in the RAS/PKA pathway (6 out of 21 multihits in tor1, 1 out of 19 in cyr1, 0 out of 5 in gpb2), while cyr1 and gpb2 mutants are more likely to acquire mutations in the TOR/Sch9 pathway (1 out of 19 in cyr1, 2 out of 5 in gpb2, 0 out of 21 in tor1). The observation that double mutants on the RAS/PKA and TOR/Sch9 pathways are more fit than their corresponding single mutants and were selected for, whereas double mutants on the same pathway were not, suggests that the TOR and RAS/PKA pathways are not redundant in how they increase fitness, as has been previously shown 51 .…”

Section: Molecular Targets Of Adaptation Are Contingent Upon the Founmentioning

confidence: 54%

Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

Aggeli

Sherlock

2020

Preprint

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The fitness effects of random mutations are contingent upon the genetic and environmental contexts in which they occur, and this contributes to the unpredictability of evolutionary outcomes at the molecular level. Despite this unpredictability, the rate of adaptation in homogeneous environments tends to decrease over evolutionary time, due to diminishing returns epistasis, causing relative fitness gains to be predictable over the long term. Here, we studied the extent of diminishing returns epistasis and the changes in the adaptive mutational spectra after yeast populations have already taken their first adaptive mutational step. We used three distinct adaptive clones that arose under identical conditions from a common ancestor, from which they diverge by a single point mutation, to found populations that we further evolved. We followed the evolutionary dynamics of these populations by lineage tracking and determined adaptive outcomes using fitness assays and whole genome sequencing. We found compelling evidence for diminishing returns: fitness gains during the 2 nd step of adaptation are smaller than those of the 1 st step, due to a compressed distribution of fitness effects in the 2 nd step. We also found strong evidence for historical contingency at the genic level: the beneficial mutational spectra of the 2 nd -step adapted genotypes differ with respect to their ancestor and to each other, despite the fact that the three founders' 1 st -step mutations provided their fitness gains due to similar phenotypic improvements. While some targets of selection in the second step are shared with those seen in the common ancestor, other targets appear to be contingent on the specific first step mutation, with more phenotypically similar founding clones having more similar adaptive mutational spectra. Finally, we found that disruptive mutations, such as nonsense and frameshift, were much more common in the first step of adaptation, contributing an additional way that both diminishing returns and historical contingency are evident during 2 nd step adaptation. Stephen Jay Gould argued that historical contingency makes evolutionary outcomes largely unpredictable, and that were we to replay the "tape of life", we would likely end up with a different world each time 1 . However, frequently observed instances of both parallel 2-4 and convergent 5-7 evolution suggest that, at least under some circumstances, adapting populations may simply take different paths to the same peak on a fitness landscape. Environmental similarities, genotypic relatedness and proximity to an optimum in the fitness landscape constitute some of the constraints contributing to convergent or parallel adaptive responses 4,8-21 .Closely related genotypes are often employed to study the effects of evolutionary history on adaptation in various experimental systems [22][23][24][25][26][27][28][29][30] . A frequent observation is that fitness gains decrease over time during adaptive evolution-termed diminishing returns-most convincingly demonstrated in cases whe...

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Section: Molecular Targets Of Adaptation Are Contingent Upon the Founmentioning

confidence: 54%

Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

Aggeli

Sherlock

2020

Preprint

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“…A recent study evaluated the contributions of PKA and TORC1 to transcriptional regulation of ribosomal biogenesis and protein synthesis genes following transfer of cells from a non-fermentable carbon source to glucose using chemical inhibitors (31). They found that while PKA was required for the regulation of ribosomal biogenesis/ protein synthesis genes during transition into glucose-containing medium, TORC1 was required for their steady state gene expression (31). Although they proposed that TORC1 regulates the ribosomal biogenesis genes by inactivating transcriptional repressors Dot6 and Tod6 via Sch9, rapamycin treatment affected the gene expression in a dot6Δ tod6Δ strain (31).…”

Section: Discussionmentioning

confidence: 99%

“…They found that while PKA was required for the regulation of ribosomal biogenesis/ protein synthesis genes during transition into glucose-containing medium, TORC1 was required for their steady state gene expression (31). Although they proposed that TORC1 regulates the ribosomal biogenesis genes by inactivating transcriptional repressors Dot6 and Tod6 via Sch9, rapamycin treatment affected the gene expression in a dot6Δ tod6Δ strain (31). This is consistent with our observations that rapamycin treatment affected the expression of the TGC genes in the sch9Δ strain ( Figure 6).…”

Section: Discussionmentioning

confidence: 99%

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TORC1 regulates the transcriptional response to glucose and developmental cycle via the Tap42-Sit4-Rrd1/2 pathway in Saccharomyces cerevisiae

Arumugam

Alfatah

Wong³

et al. 2019

Preprint

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Target of Rapamycin Complex 1 (TORC1) is a highly conserved eukaryotic protein complex that couples the presence of growth factors and nutrients in the environment with cellular proliferation. TORC1 is primarily implicated in linking amino acid levels with cellular growth in yeast and mammals. Although glucose deprivation has been shown to cause TORC1 inactivation in yeast, the precise role of TORC1 in glucose signaling and the underlying mechanisms remain unclear. In this paper, we demonstrate that the presence of glucose in the growth medium is both necessary and sufficient for TORC1 activation. TORC1 activity increases upon addition of glucose to yeast cells growing in a non-fermentable carbon source.Conversely, shifting yeast cells from glucose to a non-fermentable carbon source reduces TORC1 activity. Analysis of transcriptomic data revealed that glucose and TORC1 co-regulate about 27% (1668/6004) of yeast genes. We demonstrate that TORC1 orchestrates the expression of glucose-response genes mainly via the Tap42-Sit4-Rrd1/Rrd2 pathway. To confirm TORC1's role in glucose-signaling, we tested its role in spore germination, a glucose-dependent developmental state transition in yeast. TORC1 regulates the glucose-responsive genes during spore germination and inhibition of TORC1 blocks spore germination. We propose that a regulatory loop that involves activation of TORC1 by glucose and regulation of glucoseresponsive genes by TORC1, mediates nutritional control of growth and development in yeast.

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“…The desire to control the important aspects of our lives is common, and it may be rooted in nature [16]. In this paper, we address one aspect that is becoming increasingly important, namely online privacy regarding the disclosure of personal information.…”

Section: Introductionmentioning

confidence: 99%

Order of Control and Perceived Control over Personal Information

Shulman

Ngo

Meyer

2020

Privacy and Identity Management. Data for Better Living: AI and Privacy

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Focusing on personal information disclosure, we apply control theory and the notion of the Order of Control to study people's understanding of the implications of information disclosure and their tendency to consent to disclosure. We analyzed the relevant literature and conducted a preliminary online study (N = 220) to explore the relationship between the Order of Control and perceived control over personal information. Our analysis of existing research suggests that the notion of the Order of Control can help us understand people's decisions regarding the control over their personal information. We discuss limitations and future directions for research regarding the application of the idea of the Order of Control to online privacy.

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Integrated TORC1 and PKA signaling control the temporal activation of glucose-induced gene expression in yeast

Cited by 62 publications

References 53 publications

Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

TORC1 regulates the transcriptional response to glucose and developmental cycle via the Tap42-Sit4-Rrd1/2 pathway in Saccharomyces cerevisiae

Order of Control and Perceived Control over Personal Information

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