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R E Lenski

Publications and source records attributed to R E Lenski.

At least 37 records · Page 2Linked to original sources
PubMed1998

Evolution of competitive fitness in experimental populations of E. coli: what makes one genotype a better competitor than another?

An important problem in microbial ecology is to identify those phenotypic attributes that are responsible for competitive fitness in a particular environment. Thousands of papers have been published on the physiology, biochemistry, and molecular genetics of Escherichia coli and other bacterial models. Nonetheless, little is known about what makes one genotype a better competitor than another even in such well studied systems. Here, we review experiments to identify the phenotypic bases of improved competitive fitness in twelve E. coli populations that evolved for thousands of generations in a defined environment, in which glucose was the limiting substrate. After 10,000 generations, the average fitness of the derived genotypes had increased by approximately 50% relative to the ancestor, based on competition experiments using marked strains in the same environment. The growth kinetics of the ancestral and derived genotypes showed that the latter have a shorter lag phase upon transfer into fresh medium and a higher maximum growth rate. Competition experiments were also performed in environments where other substrates were substituted for glucose. The derived genotypes are generally more fit in competition for those substrates that use the same mechanism of transport as glucose, which suggests that enhanced transport was an important target of natural selection in the evolutionary environment. All of the derived genotypes produce much larger cells than does the ancestor, even when both types are forced to grow at the same rate. Some but not all, of the derived genotypes also have greatly elevated mutation rates. Efforts are now underway to identify the genetic changes that underlie those phenotypic changes, especially substrate specificity and elevated mutation rate for which there are good candidate loci. Identification and subsequent manipulation of these genes may provide new insights into the reproducibility of adaptive evolution, the importance of co-adapted gene complexes, and the extent to which distinct phenotypes (e.g., substrate specificity and cell size) are affected by the same mutations.

Adaptation, Physiological↗
PubMed1998

Parallel and divergent genotypic evolution in experimental populations of Ralstonia sp.

Genetic rearrangements within a population of bacteria were analyzed to understand the degree of divergence occurring after experimental evolution. We used 18 replicate populations founded from Ralstonia sp. strain TFD41 that had been propagated for 1,000 generations with 2,4-dichlorophenoxyacetic acid (2,4-D) as the carbon source. Genetic divergence was examined by restriction fragment length polymorphism analysis of the incumbent plasmid that carries the 2,4-D catabolic genes and by amplification of random regions of the genome via PCR. In 18 evolved clones examined, we observed duplication within the plasmid, including the tfdA gene, which encodes a 2,4-D dioxygenase that catalyzes the first step in the 2,4-D catabolic pathway. In 71 of 72 evolved clones, a common 2.4-kb PCR product was lost when genomic fingerprints produced by PCR amplification using degenerate primers based on repetitive extragenic palindromic (REP) sequences (REP-PCR) were compared. The nucleotide sequence of the 2.4-kb PCR product has homology to the TRAP (tripartite ATP-independent periplasmic) solute transporter gene family. Hybridization of the 2. 4-kb REP-PCR product from the ancestor to genomic DNA from the evolved populations showed that the loss of the PCR product resulted from deletions in the genome. Deletions in the plasmid and presence and/or absence of other REP-PCR products were also found in these clones but at much lower frequencies. The common and uncommon genetic changes observed show that both parallel and divergent genotypic evolution occurred in replicate populations of this bacterium.

Chlorophenols↗
PubMed1998

Bacterial evolution and the cost of antibiotic resistance.

Bacteria clearly benefit from the possession of an antibiotic resistance gene when the corresponding antibiotic is present. But do resistant bacteria suffer a cost of resistance (i.e., a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put resistance genes into naive bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments (in vitro and in vivo) show that the cost of antibiotic resistance can be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics.

Bacteria↗
PubMed1998

The fate of competing beneficial mutations in an asexual population.

In sexual populations, beneficial mutations that occur in different lineages may be recombined into a single lineage. In asexual populations, however, clones that carry such alternative beneficial mutations compete with one another and, thereby, interfere with the expected progression of a given mutation to fixation. From theoretical exploration of such 'clonal interference', we have derived (1) a fixation probability for beneficial mutations, (2) an expected substitution rate, (3) an expected coefficient of selection for realized substitutions, (4) an expected rate of fitness increase, (5) the probability that a beneficial mutation transiently achieves polymorphic frequency (> or = 1%), and (6) the probability that a beneficial mutation transiently achieves majority status. Based on (2) and (3), we were able to estimate the beneficial mutation rate and the distribution of mutational effects from changes in mean fitness in an evolving E. coli population.

Computer Simulation↗
PubMed1998

Distribution of fitness effects caused by random insertion mutations in Escherichia coli.

Very little is known about the distribution of mutational effects on organismal fitness, despite the fundamental importance of this information for the study of evolution. This lack of information reflects the fact that it is generally difficult to quantify the dynamic effects of mutation and natural selection using only static distributions of allele frequencies. In this study, we took a direct approach to measuring the effects of mutations on fitness. We used transposon-mutagenesis to create 226 mutant clones of Escherichia coli. Each mutant clone carried a single random insertion of a derivative of Tn10. All 226 mutants were independently derived from the same progenitor clone, which was obtained from a population that had evolved in a constant laboratory environment for 10,000 generations. We then performed competition experiments to measure the effect of each mutation on fitness relative to a common competitor. At least 80% of the mutations had a significant negative effect on fitness, whereas none of the mutations had a significant positive effect. The mutations reduced fitness by about 3%, on average, but the distribution of fitness effects was highly skewed and had a long, flat tail. A compound distribution, which includes both gamma and uniform components, provided an excellent fit to the observed fitness values.

Biological Evolution↗
PubMed1997

Test of synergistic interactions among deleterious mutations in bacteria.

Identifying the forces responsible for the origin and maintenance of sexuality remains one of the greatest unsolved problems in biology. The mutational deterministic hypothesis postulates that sex is an adaptation that allows deleterious mutations to be purged from the genome; it requires synergistic interactions, which means that two mutations would be more harmful together than expected from their separate effects. We generated 225 genotypes of Escherichia coli carrying one, two or three successive mutations and measured their fitness relative to an unmutated competitor. The relationship between mutation number and average fitness is nearly log-linear. We also constructed 27 recombinant genotypes having pairs of mutations whose separate and combined effects on fitness were determined. Several pairs exhibit significant interactions for fitness, but they are antagonistic as often as they are synergistic. These results do not support the mutational deterministic hypothesis for the evolution of sex.

Directed Molecular Evolution↗
PubMed1997

Evolution of high mutation rates in experimental populations of E. coli.

Most mutations are likely to be deleterious, and so the spontaneous mutation rate is generally held at a very low value. Nonetheless, evolutionary theory predicts that high mutation rates can evolve under certain circumstances. Empirical observations have previously been limited to short-term studies of the fates of mutator strains deliberately introduced into laboratory populations of Escherichia coli, and to the effects of intense selective events on mutator frequencies in E. coli. Here we report the rise of spontaneously originated mutators in populations of E. coli undergoing long-term adaptation to a new environment. Our results corroborate computer simulations of mutator evolution in adapting clonal populations, and may help to explain observations that associate high mutation rates with emerging pathogens and with certain cancers.

Adaptation, Physiological↗
PubMed1997

The cost of antibiotic resistance--from the perspective of a bacterium.

The possession of an antibiotic resistance gene clearly benefits a bacterium when the corresponding antibiotic is present. But does the resistant bacterium suffer a cost of resistance (i.e. a reduction in fitness) when the antibiotic is absent? If so, then one strategy to control the spread of resistance would be to suspend the use of a particular antibiotic until resistant genotypes declined to low frequency. Numerous studies have indeed shown that resistant genotypes are less fit than their sensitive counterparts in the absence of antibiotic, indicating a cost of resistance. But there is an important caveat: these studies have put antibiotic resistance genes into naïve bacteria, which have no evolutionary history of association with the resistance genes. An important question, therefore, is whether bacteria can overcome the cost of resistance by evolving adaptations that counteract the harmful side-effects of resistance genes. In fact, several experiments have shown that the cost of antibiotic resistance may be substantially diminished, even eliminated, by evolutionary changes in bacteria over rather short periods of time. As a consequence of this adaptation of bacteria to their resistance genes, it becomes increasingly difficult to eliminate resistant genotypes simply by suspending the use of antibiotics.

Bacteria↗
PubMed1997

Phenotypic and evolutionary adaptation of a model bacterial system to stressful thermal environments.

We studied both phenotypic and evolutionary adaptation to various thermal environments using the bacterium Escherichia coli as an experimental model system. We determined that 42 degrees C was stressful to a bacterial clone adapted to 37 degrees C, based on reductions in both absolute and competitive fitness, as well as induction of a heat stress response. This clone was also used to found replicated populations that were propagated for thousands of generations under several different thermal regimes, including 42 degrees C. Evolutionary adaptation of the populations to 42 degrees C resulted in an increase in both absolute and relative fitness at that temperature, measured respectively as an increase in the number of descendants (and their biovolume) and in competitive ability relative to the ancestral clone. The replicated experimental lineages achieved their evolutionary improvement by several distinct pathways, which produced differential preadaptation to a non-stressful nutrient environment. Adaptation to this stressful temperature entailed neither a change in the ancestral thermal niche nor any pronounced trade-offs in fitness within the thermal niche, contrary to a priori predictions. This study system was several important advantages for evaluating hypotheses concerning the effects of stress on phenotypic and evolutionary adaptation, including the ability to obtain lineages that have evolved in controlled and defined environments, to make direct measurements of fitness and to quantify the degree of stress imposed by different environments.

Adaptation, Physiological↗
PubMed1996

The curse of the pharaoh: the evolution of virulence in pathogens with long living propagules.

We used a mathematical model to evaluate the hypothesis that parasites and pathogens with long living propagules should evolve high levels of virulence, i.e. high rates of pathogen-induced host mortality. Our model shows that the optimal level of virulence is independent of the longevity of the propagules either: (i) if the density or the prevalence of infected hosts is in (or fluctuates around) equilibrium; or (ii) if the death rate of the infected host population is high compared with that of the propagules. The level of virulence that maximizes the parasite's fitness (Multhusian parameter) increases with increasing longevity of its propagules only if the host-parasite system has not reached equilibrium and the death rate of the propagules is high relative to that of the infected hosts. Therefore, for parasites that have recently invaded a susceptible host population, greater propagule longevity may initially favour higher virulence; but once the equilibrium is reached the optimal virulence is independent of propagule longevity.

Animals↗
PubMed1996

Punctuated evolution caused by selection of rare beneficial mutations.

For more than two decades there has been intense debate over the hypothesis that most morphological evolution occurs during relatively brief episodes of rapid change that punctuate much longer periods of stasis. A clear and unambiguous case of punctuated evolution is presented for cell size in a population of Escherichia coli evolving for 3000 generations in a constant environment. The punctuation is caused by natural selection as rare, beneficial mutations sweep successively through the population. This experiment shows that the most elementary processes in population genetics can give rise to punctuated evolution dynamics.

Alleles↗
PubMed1996

Long-term experimental evolution in Escherichia coli. IV. Targets of selection and the specificity of adaptation.

This study investigates the physiological manifestation of adaptive evolutionary change in 12 replicate populations of Escherichia coli that were propagated for 2000 generations in a glucose-limited environment. Representative genotypes from each population were assayed for fitness relative to their common ancestor in the experimental glucose environment and in 11 novel single-nutrient environments. After 2000 generations, the 12 derived genotypes had diverged into at least six distinct phenotypic classes. The nutrients were classified into four groups based upon their uptake physiology. All 12 derived genotypes improved in fitness by similar amounts in the glucose environment, and this pattern of parallel fitness gains was also seen in those novel environments where the limiting nutrient shared uptake mechanisms with glucose. Fitness showed little or no consistent improvement, but much greater genetic variation, in novel environments where the limiting nutrient differed from glucose in its uptake mechanisms. This pattern of fitness variation in the novel nutrient environments suggests that the independently derived genotypes adapted to the glucose environment by similar, but not identical, changes in the physiological mechanisms for moving glucose across both the inner and outer membranes.

Adaptation, Physiological↗
PubMed1996

Experimental rejection of a nonadaptive explanation for increased cell size in Escherichia coli.

Populations of Escherichia coli that have been serially propagated for thousands of generations in glucose minimal medium show heritable increases in both cell size and growth rate. We sought to test the hypothesis that the increased cell size of the derived genotypes could be explained solely by their faster growth. The regression of cell size on growth rate differed significantly between populations having ancestral and derived genotypes, with the latter producing larger cells over almost the entire range of growth rates. Thus, the physiological coupling between cell size and growth rate has been evolutionarily altered.

Adaptation, Physiological↗
PubMed1995

Experimental tests of the roles of adaptation, chance, and history in evolution.

The contributions of adaptation, chance, and history to the evolution of fitness and cell size were measured in two separate experiments using bacteria. In both experiments, populations propagated in identical environments achieved similar fitnesses, regardless of prior history or subsequent chance events. In contrast, the evolution of cell size, a trait weakly correlated with fitness, was more strongly influenced by history and chance.

Adaptation, Physiological↗
PubMed1994

Evidence for multiple adaptive peaks from populations of bacteria evolving in a structured habitat.

Natural selection tends to promote the divergence of populations living in different environments. Even in identical environments, however, replicate populations may diverge if they find alternative adaptive solutions. We describe the evolution of 18 bacterial populations (Comamonas sp.) founded from a single progenitor genotype and propagated separately for 1000 generations in two distinct environments, one physically unstructured (mass-action liquid) and the other structured (agar surfaces). Phenotypic diversity, as reflected in colony morphology, was greater in the structured habitat than in the unstructured habitat. More importantly, the trajectories for mean fitness, as measured by competition against the common ancestor, were more divergent for populations in the structured habitat than those in the unstructured habitat. Structured environments may accelerate evolutionary diversification by promoting genetic polymorphisms within populations, thereby increasing the complexity of genetic constraints that allow divergence among replicate populations.

Adaptation, Biological↗