487 research outputs found
A method for achieving prolonged nutrient limited growth of Neurospora mycelium.
A method for achieving prolonged nutrient-limited growth of Neurospora mycelium
Positive selection for elevated gene expression noise in yeast
It is well known that the expression noise is lessened by natural selection for genes that are important for cell growth or are sensitive to dosage. In theory, expression noise can also be elevated by natural selection when noisy gene expression is advantageous. Here we analyze yeast genome-wide gene expression noise data and show that plasma-membrane transporters show significantly elevated expression noise after controlling all confounding factors. We propose a model that explains why and under what conditions elevated expression noise may be beneficial and subject to positive selection. Our model predicts and the simulation confirms that, under certain conditions, expression noise also increases the evolvability of gene expression by promoting the fixation of favorable expression level-altering mutations. Indeed, yeast genes with higher noise show greater between-strain and between-species divergences in expression, even when all confounding factors are excluded. Together, our theoretical model and empirical results suggest that, for yeast genes such as plasma-membrane transporters, elevated expression noise is advantageous, is subject to positive selection, and is a facilitator of adaptive gene expression evolution
Photorespiration: metabolic pathways and their role in stress protection
Photorespiration results from the oxygenase reaction catalysed by ribulose-1,5-bisphosphate carboxylase/
oxygenase. In this reaction glycollate-2-phosphate is produced and subsequently metabolized in the
photorespiratory pathway to form the Calvin cycle intermediate glycerate-3-phosphate. During this metabolic
process, CO2 and NH3 are produced and ATP and reducing equivalents are consumed, thus
making photorespiration a wasteful process. However, precisely because of this ine¤ciency, photorespiration
could serve as an energy sink preventing the overreduction of the photosynthetic electron transport
chain and photoinhibition, especially under stress conditions that lead to reduced rates of photosynthetic
CO2 assimilation. Furthermore, photorespiration provides metabolites for other metabolic processes, e.g.
glycine for the synthesis of glutathione, which is also involved in stress protection. In this review, we
describe the use of photorespiratory mutants to study the control and regulation of photorespiratory pathways.
In addition, we discuss the possible role of photorespiration under stress conditions, such as
drought, high salt concentrations and high light intensities encountered by alpine plants
Metabolic Futile Cycles and Their Functions: A Systems Analysis of Energy and Control
It has long been hypothesized that futile cycles in cellular metabolism are
involved in the regulation of biochemical pathways. Following the work of
Newsholme and Crabtree, we develop a quantitative theory for this idea based on
open-system thermodynamics and metabolic control analysis. It is shown that the
{\it stoichiometric sensitivity} of an intermediary metabolite concentration
with respect to changes in steady-state flux is governed by the effective
equilibrium constant of the intermediate formation, and the equilibrium can be
regulated by a futile cycle. The direction of the shift in the effective
equilibrium constant depends on the direction of operation of the futile cycle.
High stoichiometric sensitivity corresponds to ultrasensitivity of an
intermediate concentration to net flow through a pathway; low stoichiometric
sensitivity corresponds to super-robustness of concentration with respect to
changes in flux. Both cases potentially play important roles in metabolic
regulation. Futile cycles actively shift the effective equilibrium by expending
energy; the magnitude of changes in effective equilibria and sensitivities is a
function of the amount of energy used by a futile cycle. This proposed
mechanism for control by futile cycles works remarkably similarly to kinetic
proofreading in biosynthesis. The sensitivity of the system is also intimately
related to the rate of concentration fluctuations of intermediate metabolites.
The possibly different roles of the two major mechanisms for cellular
biochemical regulation, namely reversible chemical modifications via futile
cycles and shifting equilibrium by macromolecular binding, are discussed.Comment: 11 pages, 5 figure
Systems approaches to modelling pathways and networks.
Peer reviewedPreprin
Evolutionary fates within a microbial population highlight an essential role for protein folding during natural selection
Physicochemical properties of molecules can be linked directly to evolutionary fates of a population in a quantitative and predictive manner.Reversible- and irreversible-folding pathways must be accounted for to accurately determine in vitro kinetic parameters (KM and kcat) at temperatures or conditions in which a significant fraction of free enzyme is unfolded.In vivo population dynamics can be reproduced using in vitro physicochemical measurements within a model that imposes an activity threshold above which there is no added fitness benefit
Gene expression drives the evolution of dominance.
Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance in natural populations is poorly quantified. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arises as a consequence of the functional importance of genes and their optimal expression levels
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