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Biomedical subjects

R E Lenski

Publications and source records attributed to R E Lenski.

At least 55 records · Page 3Linked to original sources

The evolution of virulence in parasites and pathogens: reconciliation between two competing hypotheses.

According to conventional wisdom, parasites and pathogens should evolve reduced virulence to their hosts, because more virulent parasites and pathogens are more likely to drive their hosts, and themselves, to extinction. But this view has been criticized for its reliance on group selection. According to an alternative perspective, selection will favor whatever level of virulence maximizes the rate of increase of the parasite or pathogen. This optimum virulence depends on the functional relationship between a parasite or pathogen's transmissibility and its effect on host mortality, with selection often favoring an intermediate degree of virulence. The thesis of this paper is that models in which intermediate levels of virulence are favored lead quite naturally to the further conclusion that parasites and pathogens should-up to a point-become less virulent over time, once the feedbacks between ecological and evolutionary processes are incorporated into the analysis. As a consequence of successive adaptations by the parasite or pathogen, the density of susceptible hosts is reduced, thereby altering the balance between selective forces so as to favor reduced virulence. However, the evolutionarily stable strategy that is achieved is bounded away from complete avirulence. We conclude that models in which intermediate virulence is favored do not necessarily contradict the conventional wisdom in the long run; in fact, these models provide a simple mechanistic explanation for the evolution of reduced virulence.

Animals↗

Dynamics of adaptation and diversification: a 10,000-generation experiment with bacterial populations.

We followed evolutionary change in 12 populations of Escherichia coli propagated for 10,000 generations in identical environments. Both morphology (cell size) and fitness (measured in competition with the ancestor) evolved rapidly for the first 2000 generations or so after the populations were introduced into the experimental environment, but both were nearly static for the last 5000 generations. Although evolving in identical environments, the replicate populations diverged significantly from one another in both morphology and mean fitness. The divergence in mean fitness was sustained and implies that the populations have approached different fitness peaks of unequal height in the adaptive landscape. Although the experimental time scale and environment were microevolutionary in scope, our experiments were designed to address questions concerning the origin as well as the fate of genetic and phenotypic novelties, the repeatability of adaptation, the diversification of lineages, and thus the causes and consequences of the uniqueness of evolutionary history. In fact, we observed several hallmarks of macroevolutionary dynamics, including periods of rapid evolution and stasis, altered functional relationships between traits, and concordance of anagenetic and cladogenetic trends. Our results support a Wrightian interpretation, in which chance events (mutation and drift) play an important role in adaptive evolution, as do the complex genetic interactions that underlie the structure of organisms.

Adaptation, Physiological↗

Temperature acclimation and competitive fitness: an experimental test of the beneficial acclimation assumption.

Phenotypic acclimation is generally assumed to confer an advantage in the environment that stimulates the response. To test this beneficial acclimation assumption explicitly, we investigated the consequences of temperature acclimation for the fitness of Escherichia coli at two temperatures, 32 degrees C and 41.5 degrees C. Both temperatures permit growth and long-term persistence of the genotypes in serial culture. We found that prior acclimation to 32 degrees C, relative to acclimation to 41.5 degrees C, enhanced fitness at 32 degrees C, consistent with the assumption. But prior acclimation to 41.5 degrees C actually reduced fitness at 41.5 degrees C, relative to acclimation to 32 degrees C. Hence, the assumption that acclimation always confers an advantage is demonstrated to be false. Acclimation to 41.5 degrees C did, however, improve survival at 50 degrees C, a lethal temperature. This protective response has been shown to be associated with the induction of stress proteins. The reduced competitive fitness caused by acclimation at 41.5 degrees C may reflect a physiological burden associated with expression of stress proteins when they are not needed to prevent lethal damage. Whatever the cause, acclimation to the higher temperature decreased competitive fitness at that temperature.

Acclimatization↗

Adaptive evolution of highly mutable loci in pathogenic bacteria.

Bacteria have specific loci that are highly mutable. We argue that the coexistence within bacterial genomes of such 'contingency' genes with high mutation rates, and 'housekeeping' genes with low mutation rates, is the result of adaptive evolution, and facilitates the efficient exploration of phenotypic solutions to unpredictable aspects of the host environment while minimizing deleterious effects on fitness.

Animals↗

Epistatic effects of promoter and repressor functions of the Tn10 tetracycline-resistance operon of the fitness of Escherichia coli.

We have been studying the effects of expression of plasmid-borne, Tn10-encoded, tetracycline resistance on the fitness of Escherichia coli K12. We previously demonstrated large reductions in fitness resulting from induced or constitutive expression of the resistance protein; however, any residual expression by the repressed operon was so slight that possession of an inducible resistance function imposed essentially no burden in the absence of antibiotic. Here, we demonstrate two distinct disadvantages for inducible genotypes relative to isogenic constitutive constructs. During the transition from antibiotic-free to antibiotic-containing media, the inducible genotype experiences a longer lag phase prior to growth. In the sustained presence of antibiotic, full induction of the resistance function in the inducible genotype is prevented by the continued action of its repressor. However, these disadvantages may be reduced by increasing the strength of the promoter for the resistance gene in the inducible genotype. Simultaneous consideration of the mode of gene regulation (i.e. constitutive or inducible) and the strength of the resistance-gene promoter (i.e. maximum level of expression) indicates an adaptive landscape with very strong epistasis and, perhaps, multiple fitness peaks.

Epistasis, Genetic↗

Genetic analysis of a plasmid-encoded, host genotype-specific enhancement of bacterial fitness.

In the absence of antibiotics, carriage of pACYC184 reduces the competitive fitness of an Escherichia coli B genotype that was not previously selected for plasmid carriage, relative to that of an isogenic plasmid-free competitor. However, a host genotype propagated with the plasmid for 500 generations evolved an unexpected competitive advantage from plasmid carriage, relative to its own isogenic plasmid-free segregant. We manipulated the pACYC184 genome in order to identify the plasmid-encoded function that was required for the enhancement of the coevolved host genotype's competitive fitness. Inactivation of the plasmid-encoded tetracycline resistance gene, by deletion of either the promoter region or the entire gene, eliminated the beneficial effect of plasmid carriage for the coevolved host. This beneficial effect for the coevolved host was also manifest with pBR322, which contains a tetracycline resistance gene identical to that of pACYC184 but is otherwise heterologous.

Biological Evolution↗

Evaluating the fate of genetically modified microorganisms in the environment: are they inherently less fit?

Genetically modified microorganisms hold great promise for environmental applications. Nonetheless, some may have unintended adverse effects. Of particular concern for risk assessment is the simple fact that microorganisms are self-replicating entities, so that it may be impossible to control an adverse effect simply by discontinuing further releases of the organism. It has been suggested, however, that genetically modified microorganisms will be poor competitors and therefore unable to persist in the wild due to energetic inefficiency, disruption of genomic coadaptation, or domestication. Many studies support the hypothesis that genetically modified microorganisms are less fit than their progenitors, but there are a few noteworthy counter-examples in which genetic modifications unexpectedly enhance competitive fitness. Furthermore, subsequent evolution may eliminate the maladaptive effects of some genes, increasing the likelihood that a modified organism or its engineered genes will persist. Evaluating the likelihood that a genetically modified microorganism or its engineered genes will persist is a complex ecological and evolutionary problem. Therefore, an efficient regulatory framework would require such evaluations only when there are plausible scenarios for significant adverse environmental effects.

Bacteria↗

The directed mutation controversy and neo-Darwinism.

According to neo-Darwinian theory, random mutation produces genetic differences among organisms whereas natural selection tends to increase the frequency of advantageous alleles. However, several recent papers claim that certain mutations in bacteria and yeast occur at much higher rates specifically when the mutant phenotypes are advantageous. Various molecular models have been proposed that might explain these directed mutations, but the models have not been confirmed. Critics contend that studies purporting to demonstrate directed mutation lack certain controls and fail to account adequately for population dynamics. Further experiments that address these criticisms do not support the existence of directed mutations.

Bacteria↗

Hierarchical analysis of linkage disequilibrium in Rhizobium populations: evidence for sex?

Many bacterial species exhibit strong linkage disequilibrium of their chromosomal genes, which apparently indicates restricted recombination between alleles at different loci. The extent to which restricted recombination reflects limited migration between geographically isolated populations versus infrequent mixis of genotypes within populations is more difficult to determine. We examined the genetic structure of Rhizobium leguminosarum biovar phaseoli populations associated with wild and cultivated beans (Phaseolus spp.) over several spatial scales, ranging from individual host plants to throughout the Western Hemisphere. We observed significant linkage disequilibrium at scales at least as small as a cultivated plot. However, the amount of disequilibrium was much greater among isolates collected throughout the Western Hemisphere than among isolates from one area of Mexico, even when disequilibrium was quantified using an index that scales for allelic diversity. This finding suggests that limited migration between populations contributes substantially to linkage disequilibrium in Rhizobium. We also compared the genetic structure for R. leguminosarum bv. phaseoli taken from a cultivated plot with that for Escherichia coli obtained from one human host in an earlier study. Even at this fine scale, linkage disequilibrium in E. coli was very near the theoretical maximum level, whereas it was much less extreme in the local population of Rhizobium. Thus, the genetic structure for R. leguminosarum bv. phaseoli does not exclude the possibility of frequent mixis within local populations.

Enzymes↗

Experimental evidence for an alternative to directed mutation in the bgl operon.

The directed mutation hypothesis suggests that some mutations occur more often when selectively advantageous than when neutral or disadvantageous, challenging the principle that the selective value of a mutation does not affect the rate of its occurrence. Mutations in the bgl operon of Escherichia coli have been reported to be a case of directed mutation. E. coli K12 strains chi342LD cannot grow on salicin but derivatives with two mutations in the bgl operon, an excision of IS150 (formally called IS103) from bglF and a point mutation or insertion in bflR, grow rapidly on this sugar. When chi342LD is grown on a medium containing salicin, bglF excision mutants accumulate to a frequency of greater than 1%, even though these mutants are reportedly unable to grown on salicin, and Sal+ double mutants subsequently attain a high frequency. Comparable accumulations of excision mutants and Sal+ double mutants are not observed in the absence of salicin. As salicin is not mutagenic, it has been suggested that excision mutations in bglF might serve only to create the potential for a secondary selectively advantageous mutation. We show here, however, that these double mutants can be accounted for by spontaneous mutation to intermediate genotypes in non-growing populations, coupled with slow growth of some of these intermediates on salicin, which enables their populations to reach a size where secondary mutations allowing rapid growth on salicin become common.

Benzyl Alcohols↗

Quantifying fitness and gene stability in microorganisms.

Fitness represents the combined effects of all other phenotypic properties on the capacity for survival and reproduction by a particular genotype in a particular environment. For most environmental application of genetically modified microorganisms, efficacy will be enhanced if the engineered genotype is more fit than its wild-type counterpart in the target environment. However, inadvertent spread of the engineered genotype will be less likely if it is less fit than the wild-type. Thus, the fate of a population of genetically engineered microorganisms, and the likelihood and magnitude of any environmental effects (whether beneficial or detrimental), will be strongly influenced by the relative fitnesses of modified and unmodified genotypes. In this chapter, I have presented theoretical principles and empirical methods for determining the relative fitnesses of engineered and wild-type clones. Selection coefficients were used to provide a quantitative measure of the difference in fitness between the two clones in a particular environment. Many engineered genotypes are unstable, such that their frequencies decline with time. Instability may be caused by infidelity of replication or transmission of a particular gene (which is termed segregation), or it may be caused by a difference in the fitness of genotypes that retain or have lost that gene (selection). In this chapter, I have also presented theoretical principles and empirical methods for distinguishing the effects of selection and segregation. Finally, it should be emphasized that selection coefficients and segregation rates can be estimated not only in highly simplified laboratory systems, but also in more complex natural or semi-natural systems, such as microcosms. All that is required is the ability to monitor the relative abundance of two clones (e.g., engineered and wild-type) that share a common environment.

Bacteria↗

Rapid evolution in response to high-temperature selection.

Temperature is an important environmental factor affecting all organisms, and there is ample evidence from comparative physiology that species and even conspecific populations can adapt genetically to different temperature regimes. But the effect of these adaptations on fitness and the rapidity of their evolution is unknown, as is the extent to which they depend on pre-existing genetic variation rather than new mutations. We have begun a study of the evolutionary adaptation of Escherichia coli to different temperature regimes, taking advantage of the large population sizes and short generation times in experiments on this bacterial species. We report significant improvement in temperature-specific fitness of lines maintained at 42 degrees C for 200 generations (about one month). These changes in fitness are due to selection on de novo mutations and show that some biological systems can evolve rapidly in response to changes in environmental factors such as temperature.

Biological Evolution↗

New data on excisions of Mu from E. coli MCS2 cast doubt on directed mutation hypothesis.

According to the directed mutation hypothesis, certain mutations in bacteria occur more frequently in environments in which the resulting phenotype is selectively favoured than in non-selective environments. This hypothesis therefore challenges the fundamental tenet that mutations occur spontaneously, irrespective of effects on the organism's fitness. One purported case of directed mutation is the excision of a Mu sequence from Escherichia coli strain MCS2 in minimal lactose-arabinose medium. Here, we show that this case can be more simply explained by an accelerated rate of excision mutation in response to non-specific physiological stresses of starvation and by slight growth of MCS2 on minimal lactose-arabinose medium.

Arabinose↗

Mutation and selection in bacterial populations: alternatives to the hypothesis of directed mutation.

Bacterial populations have served as model systems for studying evolutionary processes ever since the classic experiments of Luria and Delbrück, which demonstrated the occurrence of mutations prior to selection for the traits they conferred. However, several authors have recently presented experiments suggesting that bacteria may have mechanisms for directing which mutations occur, such that the rate of adaptive mutations is enhanced. Before the hypothesis of directed mutation is accepted, it is imperative to consider alternative hypotheses that might account for the same observations. To this end, we expand upon existing mathematical theory of the dynamics of mutation and selection in clonal populations for two cases of particular interest. The first case concerns selection against mutants before plating; this selection occurs as the result of differences in growth rate between mutants and nonmutants. We demonstrate that this selection model gives rise to distributions of mutants, obtained by plating from sister cultures, that are very similar to those expected when some mutations are induced by the selective environment. The second case concerns the sequential incorporation of two mutations as the result of selection for an intermediate genotype after plating. We demonstrate that this two-step mutation model also yields distributions that are similar to those expected when some mutations are induced by the selective environment. These two cases therefore provide alternatives to the hypothesis of directed mutation. We suggest experiments that might be used to examine our alternative hypotheses. We also contrast the hypothesis of directed mutation with the notion of inheritance of acquired characteristics.

Bacteria↗

Effects of carriage and expression of the Tn10 tetracycline-resistance operon on the fitness of Escherichia coli K12.

We have been examining the consequences of alternative modes of regulation of plasmid-borne, Tn10-encoded tetracycline resistance for the fitness of Escherichia coli. In a tetracycline-free environment, we measured the effects on fitness that were caused by (1) maximally induced expression of the resistance operon, (2) low-level constitutive expression of the resistance protein, (3) residual expression of the repressed resistance operon, (4) carriage of the resistance operon, (5) the remainder of the plasmid genome, and (6) hyperexpression of the repressor protein. We observed large reductions in fitness that were associated with induction and with constitutive expression of the tetracycline-resistance protein, but there was no discernible effect of hyperexpression of the repressor protein. We also observed a small reduction in fitness associated with the remainder of the plasmid genome. However, any reductions in fitness that were caused by residual expression and by carriage of the repressed operon were not more than 0.3%. We conclude that tight gene regulation has eliminated antagonistic pleiotropic effects of the resistance gene on fitness, so that possession of an inducible Tn10-encoded tetracycline-resistance operon imposes essentially no burden in the absence of antibiotic.

DNA Transposable Elements↗