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Adaptive evolution that requires multiple spontaneous mutations: mutations involving base substitutions.

ABSTRACT: A previous study has demonstrated that adaptive missense mutations occur in the trp operon of Escherichia coli. In this study it is shown that, under conditions of intense selection, a strain carrying missense mutations in both trpA and trpB reverts to Trp+ 10(8) times more frequently than would be expected if the two mutations were the result of independent events. Comparison of the single mutation rates with the double mutation rate and information obtained by sequencing DNA from double revertants show that neither our classical understanding of spontaneous mutation processes nor extant models for adaptive mutations can account for all of the observations. Despite a current lack of mechanistic understanding, it is clear that adaptive mutations can permit advantageous phenotypes that require multiple mutations to arise and that they appear enormously more frequently than would be expected.

SUBMITTER: Hall BG

PROVIDER: S-EPMC51982 | biostudies-other | 1991 Jul

REPOSITORIES: biostudies-other

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Adaptive evolution that requires multiple spontaneous mutations: mutations involving base substitutions.

Hall B G BG

Proceedings of the National Academy of Sciences of the United States of America 19910701 13

A previous study has demonstrated that adaptive missense mutations occur in the trp operon of Escherichia coli. In this study it is shown that, under conditions of intense selection, a strain carrying missense mutations in both trpA and trpB reverts to Trp+ 10(8) times more frequently than would be expected if the two mutations were the result of independent events. Comparison of the single mutation rates with the double mutation rate and information obtained by sequencing DNA from double revert ...[more]

PMID: 2062865

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Project description:Previously, we showed that adaptive substitutions in one of the three promoters of the bacteriophage ?X174 improved fitness at high-temperature by decreasing transcript levels three- to four-fold. To understand how such an extreme change in gene expression might lead to an almost two-fold increase in fitness at the adaptive temperature, we focused on stages in the life cycle of the phage that occur before and after the initiation of transcription. For both the ancestral strain and two single-substitution strains with down-regulated transcription, we measured seven phenotypic components of fitness (attachment, ejection, eclipse, virion assembly, latent period, lysis rate and burst size) during a single cycle of infection at each of two temperatures. The lower temperature, 37°C, is the optimal temperature at which phages are cultivated in the lab; the higher temperature, 42°C, exerts strong selection and is the condition under which these substitutions arose in evolution experiments. We augmented this study by developing an individual-based stochastic model of this same life cycle to explore potential explanations for our empirical results.Of the seven fitness parameters, three showed significant differences between strains that carried an adaptive substitution and the ancestor, indicating the presence of pleiotropy in regulatory evolution. 1) Eclipse was longer in the adaptive strains at both the optimal and high-temperature environments. 2) Lysis rate was greater in the adaptive strains at the high temperature. 3) Burst size for the mutants was double that of the ancestor at the high temperature, but half that at the lower temperature. Simulation results suggest that eclipse length and latent period variance can explain differences in burst sizes and fitness between the mutant and ancestral strains.Down-regulating transcription affects several steps in the phage life cycle, and all of these occur after the initiation of transcription. We attribute the apparent tradeoff between delayed progeny production and faster progeny release to improved host resource utilization at high temperature.

Project description:BackgroundAdaptive Laboratory Evolution (ALE) has emerged as an experimental approach to discover mutations that confer phenotypic functions of interest. However, the task of finding and understanding all beneficial mutations of an ALE experiment remains an open challenge for the field. To provide for better results than traditional methods of ALE mutation analysis, this work applied enrichment methods to mutations described by a multiscale annotation framework and a consolidated set of ALE experiment conditions. A total of 25,321 unique genome annotations from various sources were leveraged to describe multiple scales of mutated features in a set of 35 Escherichia coli based ALE experiments. These experiments totalled 208 independent evolutions and 2641 mutations. Additionally, mutated features were statistically associated across a total of 43 unique experimental conditions to aid in deconvoluting mutation selection pressures.ResultsIdentifying potentially beneficial, or key, mutations was enhanced by seeking coding and non-coding genome features significantly enriched by mutations across multiple ALE replicates and scales of genome annotations. The median proportion of ALE experiment key mutations increased from 62%, with only small coding and non-coding features, to 71% with larger aggregate features. Understanding key mutations was enhanced by considering the functions of broader annotation types and the significantly associated conditions for key mutated features. The approaches developed here were used to find and characterize novel key mutations in two ALE experiments: one previously unpublished with Escherichia coli grown on glycerol as a carbon source and one previously published with Escherichia coli tolerized to high concentrations of L-serine.ConclusionsThe emergent adaptive strategies represented by sets of ALE mutations became more clear upon observing the aggregation of mutated features across small to large scale genome annotations. The clarification of mutation selection pressures among the many experimental conditions also helped bring these strategies to light. This work demonstrates how multiscale genome annotation frameworks and data-driven methods can help better characterize ALE mutations, and thus help elucidate the genotype-to-phenotype relationship of the studied organism.

Dataset Information

Adaptive evolution that requires multiple spontaneous mutations: mutations involving base substitutions.

Publications

Adaptive evolution that requires multiple spontaneous mutations: mutations involving base substitutions.

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