Long-term experimental evolution in Escherichia coli. XI. Rejection of non-transitive interactions as cause of declining rate of adaptation

BACKGROUND: Experimental populations of Escherichia coli have evolved for 20,000 generations in a uniform environment. Their rate of improvement, as measured in competitions with the ancestor in that environment, has declined substantially over this period. This deceleration has been interpreted as the bacteria approaching a peak or plateau in a fitness landscape. Alternatively, this deceleration might be caused by non-transitive competitive interactions, in particular such that the measured advantage of later genotypes relative to earlier ones would be greater if they competed directly. RESULTS: To distinguish these two hypotheses, we performed a large set of competitions using one of the evolved lines. Twenty-one samples obtained at 1,000-generation intervals each competed against five genetically marked clones isolated at 5,000-generation intervals, with three-fold replication. The pattern of relative fitness values for these 315 pairwise competitions was compared with expectations under transitive and non-transitive models, the latter structured to produce the observed deceleration in fitness relative to the ancestor. In general, the relative fitness of later and earlier generations measured by direct competition agrees well with the fitness inferred from separately competing each against the ancestor. These data thus support the transitive model. CONCLUSION: Non-transitive competitive interactions were not a major feature of evolution in this population. Instead, the pronounced deceleration in its rate of fitness improvement indicates that the population early on incorporated most of those mutations that provided the greatest gains, and subsequently relied on beneficial mutations that were fewer in number, smaller in effect, or both

Environmental stress and the effects of mutation

Mutations are the ultimate fuel for evolution, but most mutations have a negative effect on fitness. It has been widely accepted that these deleterious fitness effects are, on average, magnified in stressful environments. Recent results suggest that the effects of deleterious mutations can, instead, sometimes be ameliorated in stressful environments

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Negative Epistasis and Evolvability in TEM-1 β-Lactamase--The Thin Line between an Enzyme's Conformational Freedom and Disorder.

Epistasis is a key factor in evolution since it determines which combinations of mutations provide adaptive solutions and which mutational pathways toward these solutions are accessible by natural selection. There is growing evidence for the pervasiveness of sign epistasis--a complete reversion of mutational effects, particularly in protein evolution--yet its molecular basis remains poorly understood. We describe the structural basis of sign epistasis between G238S and R164S, two adaptive mutations in TEM-1 β-lactamase--an enzyme that endows antibiotics resistance. Separated by 10 Å, these mutations initiate two separate trajectories toward increased hydrolysis rates and resistance toward second and third-generation cephalosporins antibiotics. Both mutations allow the enzyme's active site to adopt alternative conformations and accommodate the new antibiotics. By solving the corresponding set of crystal structures, we found that R164S causes local disorder whereas G238S induces discrete conformations. When combined, the mutations in 238 and 164 induce local disorder whereby nonproductive conformations that perturb the enzyme's catalytic preorganization dominate. Specifically, Asn170 that coordinates the deacylating water molecule is misaligned, in both the free form and the inhibitor-bound double mutant. This local disorder is not restored by stabilizing global suppressor mutations and thus leads to an evolutionary cul-de-sac. Conformational dynamism therefore underlines the reshaping potential of protein's structures and functions but also limits protein evolvability because of the fragility of the interactions networks that maintain protein structures

Predicting the evolution of antibiotic resistance

<p>Abstract</p> <p>Mutations causing antibiotic resistance are often associated with a cost in the absence of antibiotics. Surprisingly, a new study found that bacteria adapting to increased temperature became resistant to rifampicin. By studying the consequences of the involved mutations in different conditions and genetic backgrounds, the authors illustrate how knowledge of two fundamental genetic properties, pleiotropy and epistasis, may help to predict the evolution of antibiotic resistance.</p> <p>See research article <url>http://www.biomedcentral.com/1471-2148/13/50</url></p