scholarly journals Metabolic enzyme cost explains variable trade-offs between microbial growth rate and yield

2017 ◽  
Author(s):  
Meike T. Wortel ◽  
Elad Noor ◽  
Michael Ferris ◽  
Frank J. Bruggeman ◽  
Wolfram Liebermeister
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Metabolic Pathways ◽  
Biomass Yield ◽  
Cost Minimization ◽  
Fast Growth ◽  
Basic Question ◽  
Model Parameters ◽  
Trade Off ◽  
Trade Offs

AbstractMicrobes may maximize the number of daughter cells per time or per amount of nutrients consumed. These two strategies correspond, respectively, to the use of enzyme-efficient or substrate-efficient metabolic pathways. In reality, fast growth is often associated with wasteful, yield-inefficient metabolism, and a general thermodynamic trade-off between growth rate and biomass yield has been proposed to explain this. We studied growth rate/yield trade-offs by using a novel modeling framework, Enzyme-Flux Cost Minimization (EFCM) and by assuming that the growth rate depends directly on the enzyme investment per rate of biomass production. In a comprehensive mathematical model of core metabolism inE. coli, we screened all elementary flux modes leading to cell synthesis, characterized them by the growth rates and yields they provide, and studied the shape of the resulting rate/yield Pareto front. By varying the model parameters, we found that the rate/yield trade-off is not universal, but depends on metabolic kinetics and environmental conditions. A prominent trade-off emerges under oxygen-limited growth, where yield-inefficient pathways support a 2-to-3 times higher growth rate than yield-efficient pathways. EFCM can be widely used to predict optimal metabolic states and growth rates under varying nutrient levels, perturbations of enzyme parameters, and single or multiple gene knockouts.Author SummaryWhen cells compete for nutrients, those that grow faster and produce more offspring per time are favored by natural selection. In contrast, when cells need to maximize the cell number at a limited nutrient supply, fast growth does not matter and an efficient use of nutrients (i.e. high biomass yield) is essential. This raises a basic question about metabolism: can cells achieve high growth rates and yields simultaneously, or is there a conflict between the two goals? Using a new modeling method called Enzymatic Flux Cost Minimization (EFCM), we predict cellular growth rates and find that growth rate/yield trade-offs and the ensuing preference for enzyme-efficient or substrate-efficient metabolic pathways are not universal, but depend on growth conditions such as external glucose and oxygen concentrations.

scholarly journals Escherichia colipopulations adapt to complex, unpredictable fluctuations without any trade-offs across environments

2016 ◽  
Author(s):  
Shraddha Karve ◽  
Devika Bhave ◽  
Dhanashri Nevgi ◽  
Sutirth Dey
Keyword(s):  
Escherichia Coli ◽  
Growth Rate ◽  
Growth Rates ◽  
Complex Environments ◽  
Multiple Stresses ◽  
Trade Off ◽  
Trade Offs ◽  
Fluctuating Environments ◽  
Laboratory Populations ◽  
Lower Variation

AbstractIn nature, organisms are simultaneously exposed to multiple stresses (i.e. complex environments) that often fluctuate unpredictably. While both these factors have been studied in isolation, the interaction of the two remains poorly explored. To address this issue, we selected laboratory populations ofEscherichia coliunder complex (i.e. stressful combinations of pH, H2O2and NaCl) unpredictably fluctuating environments for ~900 generations. We compared the growth rates and the corresponding trade-off patterns of these populations to those that were selected under constant values of the component stresses (i.e. pH, H2O2and NaCl) for the same duration. The fluctuation-selected populations had greater mean growth rate and lower variation for growth rate over all the selection environments experienced. However, while the populations selected under constant stresses experienced severe tradeoffs in many of the environments other than those in which they were selected, the fluctuation-selected populations could by-pass the across-environment trade-offs completely. Interestingly, trade-offs were found between growth rates and carrying capacities. The results suggest that complexity and fluctuations can strongly affect the underlying trade-off structure in evolving populations.

scholarly journals Escherichia coli populations adapt to complex, unpredictable fluctuations by minimizing trade-offs across environments

2016 ◽  
Author(s):  
Shraddha Madhav Karve ◽  
Devika Bhave ◽  
Dhanashri Nevgi ◽  
Sutirth Dey
Keyword(s):  
Escherichia Coli ◽  
Growth Rate ◽  
Growth Rates ◽  
Complex Environments ◽  
Multiple Stresses ◽  
Trade Off ◽  
Trade Offs ◽  
Fluctuating Environments ◽  
Laboratory Populations ◽  
Lower Variation

In nature, organisms are simultaneously exposed to multiple stresses (i.e. complex environments) that often fluctuate unpredictably. While both these factors have been studied in isolation, the interaction of the two remains poorly explored. To address this issue, we selected laboratory populations of Escherichia coli under complex (i.e. stressful combinations of pH, H2O2 and NaCl) unpredictably fluctuating environments for ~900 generations. We compared the growth rates and the corresponding trade-off patterns of these populations to those that were selected under constant values of the component stresses (i.e. pH, H2O2 and NaCl) for the same duration. The fluctuation-selected populations had greater mean growth rate and lower variation for growth rate over all the selection environments experienced. However, while the populations selected under constant stresses experienced trade-offs in the environments other than those in which they were selected, the fluctuation-selected populations could by-pass the across-environment trade-offs almost entirely. Interestingly, trade-offs were found between growth rates and carrying capacities. The results suggest that complexity and fluctuations can strongly affect the underlying trade-off structure in evolving populations.

scholarly journals Geographic Variation in the Trade-Off Between Nestling Growth Rate and Body Condition in the Tree Swallow

The Condor ◽  
2006 ◽  
Vol 108 (3) ◽  
pp. 601-611 ◽  
Author(s):  
Daniel R. Ardia
Keyword(s):  
New York ◽  
Growth Rate ◽  
Body Mass ◽  
Body Condition ◽  
Growth Rates ◽  
Tree Swallow ◽  
Residual Body ◽  
Trade Off ◽  
Nestling Growth ◽  
Trade Offs

AbstractNestlings can exhibit considerable variation in developmental patterns both within and among locations due to differences in environmental conditions and parental investment. I investigated trade-offs between nestling growth rate and residual body mass (body condition) at three locations across the range of the Tree Swallow (Tachycineta bicolor). Nestlings at the northern extreme of the range in Alaska had slower growth rates, lower body mass, and higher residual body mass than nestlings in New York and Tennessee. High insect availability was correlated with increased growth rates of nestlings in New York and Tennessee, but not in Alaska. Conversely, nestlings in Alaska showed increased residual body mass with high insect availability, but nestlings in New York and Tennessee did not. The trade-off between growth rate and residual body mass varied among sites, with fast-growing nestlings in Tennessee maintaining a higher residual body mass than those in Alaska. These results suggest that factors affecting offspring growth and condition vary among sites, leading to geographical differences in offspring development trajectories.

ℵ0-categorical structures with arbitrarily fast growth of algebraic closure

2002 ◽  
Vol 67 (3) ◽  
pp. 897-909
Author(s):  
David M. Evans ◽  
M. E. Pantano
Keyword(s):  
Growth Rate ◽  
Automorphism Group ◽  
Finite Subset ◽  
Growth Rates ◽  
Algebraic Closure ◽  
Fast Growth ◽  
Permutation Groups ◽  
Natural Numbers ◽  
Categorical Structure ◽  
Image Position

Various results have been proved about growth rates of certain sequences of integers associated with infinite permutation groups. Most of these concern the number of orbits of the automorphism group of an ℵ0-categorical structure on the set of unordered n-subsets or on the set of n-tuples of elements of . (Recall that by the Ryll-Nardzewski Theorem, if is countable and ℵ0-categorical, the number of the orbits of its automorphism group Aut() on the set of n-tuples from is finite and equals the number of complete n-types consistent with the theory of .) The book [Ca90] is a convenient reference for these results. One of the oldest (in the realms of ‘folklore’) is that for any sequence (Kn)n∈ℕ of natural numbers there is a countable ℵ0-categorical structure such that the number of orbits of Aut() on the set of n-tuples from is greater than kn for all n.These investigations suggested the study of the growth rate of another sequence. Let be an ℵ0-categorical structure and X be a finite subset of . Let acl(X) be the algebraic closure of X, that is, the union of the finite X-definable subsets of . Equivalently, this is the union of the finite orbits on of Aut()(X), the pointwise stabiliser of X in Aut(). Define

scholarly journals A mechanistic link between cellular trade-offs, gene expression and growth

2015 ◽  
Author(s):  
Andrea Y. Weisse ◽  
Diego A. Oyarzun ◽  
Vincent Danos ◽  
Peter S. Swain
Keyword(s):  
Gene Expression ◽  
Growth Rate ◽  
Metabolic Pathways ◽  
Mechanistic Model ◽  
Living Cells ◽  
Coarse Grained ◽  
Empirical Relationships ◽  
Cellular Energy ◽  
Modelling Framework ◽  
Trade Offs

Intracellular processes rarely work in isolation but continually interact with the rest of the cell. In microbes, for example, we now know that gene expression across the whole genome typically changes with growth rate. The mechanisms driving such global regulation, however, are not well understood. Here we consider three trade-offs that because of limitations in levels of cellular energy, free ribosomes, and proteins are faced by all living cells and construct a mechanistic model that comprises these trade-offs. Our model couples gene expression with growth rate and growth rate with a growing population of cells. We show that the model recovers Monod's law for the growth of microbes and two other empirical relationships connecting growth rate to the mass fraction of ribosomes. Further, we can explain growth related effects in dosage compensation by paralogs and predict host-circuit interactions in synthetic biology. Simulating competitions between strains, we find that the regulation of metabolic pathways may have evolved not to match expression of enzymes to levels of extracellular substrates in changing environments but rather to balance a trade-off between exploiting one type of nutrient over another. Although coarse-grained, the trade-offs that the model embodies are fundamental, and, as such, our modelling framework has potentially wide application, including in both biotechnology and medicine.

scholarly journals Seedling growth rates and light requirements of subtropical rainforest trees associated with basaltic and rhyolitic soils

2014 ◽  
Vol 62 (1) ◽  
pp. 48 ◽  
Author(s):  
C. H. Lusk ◽  
K. M. Sendall ◽  
P. J. Clarke
Keyword(s):  
Leaf Area ◽  
Seedling Growth ◽  
Growth Rates ◽  
Shade Tolerance ◽  
Light Availability ◽  
Trade Off ◽  
Respiration Rates ◽  
Trade Offs ◽  
Light Requirements ◽  
Differential Adaptation

A trade-off between shade tolerance and growth in open conditions is widely believed to underlie the dynamics of humid forests. Little is known about how the growth versus shade tolerance trade-off interacts with other major trade-offs associated with differential adaptation to major environmental factors besides light. We asked whether the growth versus shade tolerance trade-off differed between subtropical rainforest tree assemblages native to basaltic (fertile) and rhyolitic (infertile) soils in northern New South Wales, because of the allocational costs of adaptation to low nutrient availability. Seedling relative growth rates of six basalt specialists and five rhyolite specialists were measured in a glasshouse and the minimum light requirements of each species were quantified in the field by determining the 10th percentile of juvenile tree distributions in relation to understorey light availability. A similar range of light requirements was observed in the two assemblages, and although the two fastest growing species were basalt specialists, seedling growth rates did not differ significantly between the two substrates. The overall relationship between light requirements and growth rate was weak, and there was no compelling evidence that the slope or elevation of this relationship differed between the two assemblages. Growth rates were significantly correlated, overall, with specific leaf area, and marginally with leaf area ratio. The apparent similarity of the growth versus shade tolerance trade-off in the two suites of species could reflect effects of leaf nutrient content on respiration rates; basalt specialists tended to have a smaller root mass fraction, but this may have been offset by the effects of leaf nitrogen status on respiration rates, with higher respiration rates expected on fertile basaltic soils. However, the results might also partly reflect impairment of the field performance of two basalt specialists that were heavily attacked by natural enemies.

Growth-enhanced transgenic salmon can be inferior swimmers

1997 ◽  
Vol 75 (2) ◽  
pp. 335-337 ◽  
Author(s):  
Anthony P. Farrell ◽  
William Bennett ◽  
Robert H. Devlin
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Coho Salmon ◽  
Swimming Performance ◽  
Oncorhynchus Kisutch ◽  
Transgenic Fish ◽  
Growth Hormone Gene ◽  
Critical Swimming Speed ◽  
Trade Off ◽  
Physiological Fitness

We examined the consequence of remarkably fast growth rates in transgenic fish, using swimming performance as a physiological fitness variable. Substantially faster growth rates were achieved by the insertion of an "all-salmon" growth hormone gene construct in transgenic coho salmon (Oncorhynchus kisutch). On an absolute speed basis, transgenic fish swam no faster at their critical swimming speed than smaller non-transgenic controls, and much slower than older non-transgenic controls of the same size. Thus, we find a marked trade-off between growth rate and swimming performance, and these results suggest that transgenic fish may be an excellent model to evaluate existing ideas regarding physiological design.

scholarly journals Deciphering the Principles of Bacterial Nitrogen Dietary Preferences: a Strategy for Nutrient Containment

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Jilong Wang ◽  
Dalai Yan ◽  
Ray Dixon ◽  
Yi-Ping Wang
Keyword(s):  
Amino Acids ◽  
Growth Rate ◽  
Growth Rates ◽  
Regulatory Networks ◽  
Metabolic Flux ◽  
Nitrogen Sources ◽  
Fast Growth ◽  
Ammonia Assimilation ◽  
Wild Type ◽  
Dietary Preferences

ABSTRACT A fundamental question in microbial physiology concerns why organisms prefer certain nutrients to others. For example, among different nitrogen sources, ammonium is the preferred nitrogen source, supporting fast growth, whereas alternative nitrogen sources, such as certain amino acids, are considered to be poor nitrogen sources, supporting much slower exponential growth. However, the physiological/regulatory logic behind such nitrogen dietary choices remains elusive. In this study, by engineering Escherichia coli , we switched the dietary preferences toward amino acids, with growth rates equivalent to that of the wild-type strain grown on ammonia. However, when the engineered strain was cultured together with wild-type E. coli , this growth advantage was diminished as a consequence of ammonium leakage from the transport-and-catabolism (TC)-enhanced (TCE) cells, which are preferentially utilized by wild-type bacteria. Our results reveal that the nitrogen regulatory (Ntr) system fine tunes the expression of amino acid transport and catabolism components to match the flux through the ammonia assimilation pathway such that essential nutrients are retained, but, as a consequence, the fast growth rate on amino acids is sacrificed. IMPORTANCE Bacteria exhibit different growth rates under various nutrient conditions. These environmentally related behaviors reflect the coordination between metabolism and the underlying regulatory networks. In the present study, we investigated the intertwined nitrogen metabolic and nitrogen regulatory systems to understand the growth differences between rich and poor nitrogen sources. Although maximal growth rate is considered to be evolutionarily advantageous for bacteria (as remarked by François Jacob, who said that the “dream” of every cell is to become two cells), we showed that negative-feedback loops in the regulatory system inhibit growth rates on amino acids. We demonstrated that in the absence of regulatory feedback, amino acids are capable of supporting fast growth rates, but this results in ammonia leaking out from cells as “waste,” benefiting the growth of competitors. These findings provide important insights into the regulatory logic that controls metabolic flux and ensures nutrient containment but consequently sacrifices growth rate.

scholarly journals XMAP215 promotes microtubule catastrophe by disrupting the growing microtubule end

2020 ◽  
Author(s):  
Veronica Farmer ◽  
Göker Arpağ ◽  
Sarah Hall ◽  
Marija Zanic
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Fast Growth ◽  
Fast Growing ◽  
Microtubule Stability ◽  
Large Fluctuations ◽  
Microtubule Growth ◽  
Enhanced Stability

ABSTRACTThe GTP-tubulin cap is widely accepted to protect microtubules against catastrophe. The GTP-cap size is thought to increase with the microtubule growth rate, presumably endowing fast-growing microtubules with enhanced stability. It is unknown what GTP-cap properties permit frequent microtubule catastrophe despite fast growth. Here, we investigate microtubules grown in vitro in the presence and absence of the microtubule polymerase XMAP215. Using EB1 as a GTP-cap marker, we find that GTP-cap size increases regardless of whether growth acceleration is achieved by increasing tubulin concentration or by XMAP215. In spite of the increased mean GTP-cap size, microtubules grown with XMAP215 display increased catastrophe frequency, in contrast to microtubules grown with more tubulin, for which catastrophe is abolished. However, microtubules polymerized with XMAP215 have large fluctuations in growth rate and EB1 intensity; display tapered and curled ends; and undergo catastrophe at faster growth rates and with higher EB1 end-localization. Our results underscore the role of growth irregularities in overall microtubule stability.

scholarly journals The number of active metabolic pathways is bounded by the number of cellular constraints at maximal metabolic rates

2017 ◽  
Author(s):  
Daan H. de Groot ◽  
Coco van Boxtel ◽  
Robert Planqué ◽  
Frank J. Bruggeman ◽  
Bas Teusink
Keyword(s):  
Growth Rate ◽  
Growth Rates ◽  
Metabolic Pathways ◽  
Extremum Principle ◽  
Overflow Metabolism ◽  
Large Network ◽  
Metabolic Rates ◽  
Enzyme Expression ◽  
Membrane Area ◽  
Metabolic Flux Distribution

AbstractGrowth rate is a near-universal selective pressure across microbial species. High growth rates require hundreds of metabolic enzymes, each with different nonlinear kinetics, to be precisely tuned within the bounds set by physicochemical constraints. Yet, the metabolic behaviour of many species is characterized by simple relations between growth rate, enzyme expression levels and metabolic rates. We asked if this simplicity could be the outcome of optimisation by evolution. Indeed, when the growth rate is maximized –in a static environment under mass-conservation and enzyme expression constraints– we prove mathematically that the resulting optimal metabolic flux distribution is described by a limited number of subnetworks, known as Elementary Flux Modes (EFMs). We show that, because EFMs are the minimal subnetworks leading to growth, a small active number automatically leads to the simple relations that are measured. We find that the maximal number of flux-carrying EFMs is determined only by the number of imposed constraints on enzyme expression, not by the size, kinetics or topology of the network. This minimal-EFM extremum principle is illustrated in a graphical framework, which explains qualitative changes in microbial behaviours, such as overflow metabolism and co-consumption, and provides a method for identification of the enzyme expression constraints that limit growth under the prevalent conditions. The extremum principle applies to all microorganisms that are selected for maximal growth rates under protein concentration constraints, for example the solvent capacities of cytosol, membrane or periplasmic space.Author summaryThe microbial genome encodes for a large network of enzyme-catalyzed reactions. The reaction rates depend on concentrations of enzymes and metabolites, which in turn depend on those rates. Cells face a number of biophysical constraints on enzyme expression, for example due to a limited membrane area or cytosolic volume. Considering this complexity and nonlinearity of metabolism, how is it possible, that experimental data can often be described by simple linear models? We show that it is evolution itself that selects for simplicity. When reproductive rate is maximised, the number of active independent metabolic pathways is bounded by the number of growth-limiting enzyme constraints, which is typically small. A small number of pathways automatically generates the measured simple relations. We identify the importance of growth-limiting constraints in shaping microbial behaviour, by focussing on their mechanistic nature. We demonstrate that overflow metabolism – an important phenomenon in bacteria, yeasts, and cancer cells – is caused by two constraints on enzyme expression. We derive experimental guidelines for constraint identification in microorganisms. Knowing these constraints leads to increased understanding of metabolism, and thereby to better predictions and more effective manipulations.

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