scholarly journals Glucose limitation inLactococcusshapes a single-peaked fitness landscape exposing membrane occupancy as a constraint

2017 ◽  
Author(s):  
Claire E. Price ◽  
Filipe Branco dos Santos ◽  
Anne Hesseling ◽  
Jaakko J. Uusitalo ◽  
Herwig Bachmann ◽  
...  

ABSTRACTA central theme in biology is to understand the molecular basis of fitness: which strategies succeed under which conditions; how are they mechanistically implemented; and which constraints shape trade-offs between alternative strategies. We approached these questions with parallel bacterial evolution experiments in chemostats. Chemostats provide a constant environment with a defined resource limitation (glucose), in which the growth rate can be controlled. UsingLactococcus lactis, we found a single mutation in a global regulator of carbon metabolism, CcpA, to confer predictable fitness improvements across multiple growth rates.In silicoprotein structural analysis complemented with biochemical and phenotypic assays, show that the mutation reprograms the CcpA regulon, specifically targeting transporters. This supports that membrane occupancy, rather than biosynthetic capacity, is the dominant constraint for the observed fitness enhancement. It also demonstrates that cells can modulate a pleiotropic regulator to work around limiting constraints.

2003 ◽  
Vol 185 (10) ◽  
pp. 3139-3146 ◽  
Author(s):  
Evelyne Krin ◽  
Christine Laurent-Winter ◽  
Philippe N. Bertin ◽  
Antoine Danchin ◽  
Annie Kolb

ABSTRACT The cAMP-catabolite activator protein (CAP) complex is a pleiotropic regulator that regulates a vast number of Escherichia coli genes, including those involved in carbon metabolism. We identified two new targets of this complex: argG, which encodes the arginosuccinate synthase involved in the arginine biosynthetic pathway, and metY, which encodes one of the two methionine tRNA initiators, tRNAf2Met. The cAMP-CAP complex activates argG transcription and inhibits metY transcription from the same DNA position. We also show that ArgR, the specific repressor of the arginine biosynthetic pathway, together with its arginine cofactor, acts on the regulation of metY mediated by CAP. The regulation of the two divergent promoters is thus simultaneously controlled not only by the cAMP-CAP complex, a global regulator, but also by a specific regulator of arginine metabolism, suggesting a previously unsuspected link between carbon metabolism and translation initiation.


2018 ◽  
Author(s):  
Elias Ehrlich ◽  
Nadja J. Kath ◽  
Ursula Gaedke

Functional trait compositions of communities can adapt to altered environmental conditions ensuring community persistence. Theory predicts that the shape of trade-offs between traits crucially affects these trait dynamics, but its empirical verification from the field is missing. Here, we show how the shape of a defense-growth trade-off governs seasonal trait dynamics of a natural community, using high-frequency, long-term measurements of phytoplankton from Lake Constance. As expected from the lab-derived concave trade-off curve, we observed an alternating dominance of several fast-growing species with intermediate defense levels and gradual changes of the biomass-trait distribution due to seasonally changing grazing pressure. By combining data and modelling, we obtain mechanistic insights on the underlying fitness landscape, and show that low fitness differences can maintain trait variation along the trade-off curve. We provide firm evidence for a frequently assumed trade-off and conclude that quantifying its shape allows to understand environmentally driven trait changes within communities.


Oikos ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 109-121 ◽  
Author(s):  
Pär Byström ◽  
Jens Andersson ◽  
Lennart Persson ◽  
André M. De Roos

2010 ◽  
Vol 192 (17) ◽  
pp. 4517-4521 ◽  
Author(s):  
Ram Maharjan ◽  
Zhemin Zhou ◽  
Yan Ren ◽  
Yang Li ◽  
Joël Gaffé ◽  
...  

ABSTRACT Beneficial mutations in diversifying glucose-limited Escherichia coli populations are mostly unidentified. The genome of an evolved isolate with multiple differences from that of the ancestor was fully assembled. Remarkably, a single mutation in hfq was responsible for the multiple benefits under glucose limitation through changes in at least five regulation targets.


Evolution ◽  
2013 ◽  
Vol 68 (3) ◽  
pp. 760-771 ◽  
Author(s):  
Sean Michael Carroll ◽  
Ming-Chun Lee ◽  
Christopher J. Marx
Keyword(s):  

1994 ◽  
Vol 14 (6) ◽  
pp. 3729-3741 ◽  
Author(s):  
L K Gauen ◽  
Y Zhu ◽  
F Letourneur ◽  
Q Hu ◽  
J B Bolen ◽  
...  

The tyrosine-based activation motif is a 20- to 25-amino-acid sequence contained in the cytoplasmic domains of many hematopoietic receptors which is sufficient by itself to reconstitute signalling. This motif is characterized by two YXXL/I sequences separated by approximately 10 residues. The molecular basis of signalling by this motif is unknown. Here we demonstrate that the tyrosine-based activation motif is required and sufficient for association with the tyrosine kinases p59fyn and ZAP-70, suggesting that association with these kinases is a general feature of this motif. Focusing on the single activation motif present in epsilon, we analyzed which residues of the motif were critical for binding of p59fyn and ZAP-70. Surprisingly, we found that no single mutation of any residue of epsilon resulted in the loss of p59fyn association. In contrast, single mutations at five residues of the epsilon activating motif abrogated ZAP-70 binding. Both of the tyrosines and the leucine or isoleucine residues that follow them were critical. The spacing between the tyrosines was also important, as deletion of two residues disrupted binding of ZAP-70, although p59fyn binding was not disrupted. Most of the defined features of the tyrosine activation motif are therefore requirements for ZAP-70 binding. Interestingly, the interaction of ZAP-70 with the motif was dependent on the presence of both ZAP-70 SH2 domains and both of the tyrosine residues in the motif, suggesting that ZAP-70 interacts with two phosphotyrosine residues and that the binding of the two SH2 domains is cooperative. In addition, we demonstrate that the interaction between the tyrosine activation motif is direct and requires prior tyrosine phosphorylation of the motif. We propose that the activation of cells by the tyrosine activating motif occurs in four discrete steps: binding of p59fyn, phosphorylation of the motif, binding of ZAP-70, and activation of ZAP-70 kinase activity.


2012 ◽  
Vol 78 (17) ◽  
pp. 6357-6364 ◽  
Author(s):  
Marion Dalmasso ◽  
Julie Aubert ◽  
Sergine Even ◽  
Hélène Falentin ◽  
Marie-Bernadette Maillard ◽  
...  

ABSTRACTSevenPropionibacterium freudenreichiistrains exhibited similar responses when placed at 4°C. They slowed down cell machinery, displayed cold stress responses, and rerouted their carbon metabolism toward trehalose and glycogen synthesis, both accumulated in cells. These results highlight the molecular basis of long-term survival ofP. freudenreichiiin the cold.


2018 ◽  
Author(s):  
Jeffrey I. Boucher ◽  
Troy W. Whitfield ◽  
Ann Dauphin ◽  
Gily Nachum ◽  
Carl Hollins ◽  
...  

AbstractThe evolution of HIV-1 protein sequences should be governed by a combination of factors including nucleotide mutational probabilities, the genetic code, and fitness. The impact of these factors on protein sequence evolution are interdependent, making it challenging to infer the individual contribution of each factor from phylogenetic analyses alone. We investigated the protein sequence evolution of HIV-1 by determining an experimental fitness landscape of all individual amino acid changes in protease. We compared our experimental results to the frequency of protease variants in a publicly available dataset of 32,163 sequenced isolates from drug-naïve individuals. The most common amino acids in sequenced isolates supported robust experimental fitness, indicating that the experimental fitness landscape captured key features of selection acting on protease during viral infections of hosts. Amino acid changes requiring multiple mutations from the likely ancestor were slightly less likely to support robust experimental fitness than single mutations, consistent with the genetic code favoring chemically conservative amino acid changes. Amino acids that were common in sequenced isolates were predominantly accessible by single mutations from the likely protease ancestor. Multiple mutations commonly observed in isolates were accessible by mutational walks with highly fit single mutation intermediates. Our results indicate that the prevalence of multiple base mutations in HIV-1 protease is strongly influenced by mutational sampling.


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