RESUMEN
Microbes are evolutionarily robust organisms capable of rapid adaptation to complex stress, which enables them to colonize harsh environments. In nature, microbes are regularly challenged by starvation, which is a particularly complex stress because resource limitation often co-occurs with changes in pH, osmolarity, and toxin accumulation created by metabolic waste. Often overlooked are the additional complications introduced by eventual resource replenishment, as successful microbes must withstand rapid environmental shifts before swiftly capitalizing on replenished resources to avoid invasion by competing species. To understand how microbes navigate trade-offs between growth and survival, ultimately adapting to thrive in environments with extreme fluctuations, we experimentally evolved 16 Escherichia coli populations for 900 days in repeated feast/famine conditions with cycles of 100-day starvation before resource replenishment. Using longitudinal population-genomic analysis, we found that evolution in response to extreme feast/famine is characterized by narrow adaptive trajectories with high mutational parallelism and notable mutational order. Genetic reconstructions reveal that early mutations result in trade-offs for biofilm and motility but trade-ups for growth and survival, as these mutations conferred positively correlated advantages during both short-term and long-term culture. Our results demonstrate how microbes can navigate the adaptive landscapes of regularly fluctuating conditions and ultimately follow mutational trajectories that confer benefits across diverse environments.
Asunto(s)
Adaptación Fisiológica , Escherichia coli , Mutación , Adaptación Fisiológica/genéticaRESUMEN
Ecological and demographic factors can significantly shape the evolution of microbial populations both directly and indirectly, as when changes in the effective population size affect the efficiency of natural selection on the mutation rate. However, it remains unclear how rapidly the mutation-rate responds evolutionarily to the entanglement of ecological and population-genetic factors over time. Here, we directly assess the mutation rate and spectrum of Escherichia coli clones isolated from populations evolving in response to 1000 days of different transfer volumes and resource-replenishment intervals. The evolution of mutation rates proceeded rapidly in response to demographic and/or environmental changes, with substantial bidirectional shifts observed as early as 59 generations. These results highlight the remarkable rapidity by which mutation rates are shaped in asexual lineages in response to environmental and population-genetic forces, and are broadly consistent with the drift-barrier hypothesis for the evolution of mutation rates, while also highlighting situations in which mutator genotypes may be promoted by positive selection.
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Genética de Población , Tasa de Mutación , Escherichia coli/genética , Genotipo , Selección GenéticaRESUMEN
All organisms are defined by the makeup of their DNA. Over billions of years, the structure and information contained in that DNA, often referred to as genetic architecture, have been honed by a multitude of evolutionary processes. Mutations that cause genetic elements to change in a way that results in beneficial phenotypic change are more likely to survive and propagate through the population in a process known as adaptation. Recent work reveals that the genetic targets of adaptation are varied and can change with genetic background. Further, seemingly similar adaptive mutations, even within the same gene, can have diverse and unpredictable effects on phenotype. These challenges represent major obstacles in predicting adaptation and evolution. In this review, we cover these concepts in detail and identify three emerging synergistic solutions: higher-throughput evolution experiments combined with updated genotype-phenotype mapping strategies and physiological models. Our review largely focuses on recent literature in yeast, and the field seems to be on the cusp of a new era with regard to studying the predictability of evolution.
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Adaptación Fisiológica , Evolución Biológica , Adaptación Fisiológica/genética , Genotipo , Mutación , Fenotipo , Saccharomyces cerevisiae/genéticaRESUMEN
Ecotypic diversification and its associated cooperative behaviors are frequently observed in natural microbial populations whose access to resources is often sporadic. However, the extent to which fluctuations in resource availability influence the emergence of cooperative ecotypes is not fully understood. To determine how exposure to repeated resource limitation affects the establishment and long-term maintenance of ecotypes in a structured environment, we followed 32 populations of Escherichia coli evolving to either 1-day or 10-day feast/famine cycles for 900 days. Population-level analysis revealed that compared to populations evolving to 1-day cycles, 10-day populations evolved increased biofilm density, higher parallelism in mutational targets, and increased mutation rates. As previous investigations of evolution in structured environments have identified biofilm formation as the earliest observable phenotype associated with diversification of ecotypes, we revived cultures midway through the evolutionary process and conducted additional genomic, transcriptional, and phenotypic analyses of clones isolated from these evolving populations. We found not only that 10-day feast/famine cycles support multiple ecotypes but also that these ecotypes exhibit cooperative behavior. Consistent with the black queen hypothesis, or evolution of cooperation by gene loss, transcriptomic evidence suggests the evolution of bidirectional cross-feeding behaviors based on essential resources. These results provide insight into how analogous cooperative relationships may emerge in natural microbial communities. IMPORTANCE Despite regular feast and famine conditions representing an environmental pressure that is commonly encountered by microbial communities, the evolutionary outcomes of repeated cycles of feast and famine have been less studied. By experimentally evolving initially isogenic Escherichia coli populations to 10-day feast/famine cycles, we observed rapid diversification into ecotypes with evidence of bidirectional cross-feeding on costly resources and frequency-dependent fitness. Although unidirectional cross-feeding has been repeatedly observed to evolve in laboratory culture, most investigations of bidirectional cooperative behaviors in microbial populations have been conducted in engineered communities. This work demonstrates the de novo evolution of black queen relationships in a microbial population originating from a single ancestor, providing a model for investigation of the eco-evolutionary processes leading to mutualistic cooperation.
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Ecotipo , Escherichia coli , Escherichia coli/genética , Genómica , FenotipoRESUMEN
How microbes adapt to a novel environment is a central question in evolutionary biology. Although adaptive evolution must be fueled by beneficial mutations, whether higher mutation rates facilitate the rate of adaptive evolution remains unclear. To address this question, we cultured Escherichia coli hypermutating populations, in which a defective methyl-directed mismatch repair pathway causes a 140-fold increase in single-nucleotide mutation rates. In parallel with wild-type E. coli, populations were cultured in tubes containing Luria-Bertani broth, a complex medium known to promote the evolution of subpopulation structure. After 900 days of evolution, in three transfer schemes with different population-size bottlenecks, hypermutators always exhibited similar levels of improved fitness as controls. Fluctuation tests revealed that the mutation rates of hypermutator lines converged evolutionarily on those of wild-type populations, which may have contributed to the absence of fitness differences. Further genome-sequence analysis revealed that, although hypermutator populations have higher rates of genomic evolution, this largely reflects strong genetic linkage. Despite these linkage effects, the evolved population exhibits parallelism in fixed mutations, including those potentially related to biofilm formation, transcription regulation, and mutation-rate evolution. Together, these results are generally inconsistent with a hypothesized positive relationship between the mutation rate and the adaptive speed of evolution, and provide insight into how clonal adaptation occurs in novel environments.
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Proteínas de Escherichia coli , Escherichia coli , Adaptación Fisiológica/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Evolución Molecular , Mutación , Tasa de MutaciónRESUMEN
Phenotypic plasticity refers to environment-induced phenotypic changes without mutation and is present in all organisms. The role of phenotypic plasticity in organismal adaptations to novel environments has attracted much attention, but its role in readaptations to ancestral environments is understudied. To address this question, we use the reciprocal transplant approach to investigate the multitissue transcriptomes of chickens adapted to the Tibetan Plateau and adjacent lowland. While many genetic transcriptomic changes had occurred in the forward adaptation to the highland, plastic changes largely transform the transcriptomes to the preferred state when Tibetan chickens are brought back to the lowland. The same trend holds for egg hatchability, a key component of the chicken fitness. These findings, along with highly similar patterns in comparable experiments of guppies and Escherichia coli, demonstrate that organisms generally "remember" their ancestral environments via phenotypic plasticity and reveal a mechanism by which past experience affects future evolution.
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The ability to obtain genome-wide sequences of very large numbers of individuals from natural populations raises questions about optimal sampling designs and the limits to extracting information on key population-genetic parameters from temporal-survey data. Methods are introduced for evaluating whether observed temporal fluctuations in allele frequencies are consistent with the hypothesis of random genetic drift, and expressions for the expected sampling variances for the relevant statistics are given in terms of sample sizes and numbers. Estimation methods and aspects of statistical reliability are also presented for the mean and temporal variance of selection coefficients. For nucleotide sites that pass the test of neutrality, the current effective population size can be estimated by a method of moments, and expressions for its sampling variance provide insight into the degree to which such methodology can yield meaningful results under alternative sampling schemes. Finally, some caveats are raised regarding the use of the temporal covariance of allele-frequency change to infer selection. Taken together, these results provide a statistical view of the limits to population-genetic inference in even the simplest case of a closed population.
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Flujo Genético , Genética de Población , Modelos Genéticos , Densidad de Población , Selección Genética , Frecuencia de los Genes , Humanos , Tamaño de la MuestraRESUMEN
Organismal adaptations to new environments often begin with plastic phenotypic changes followed by genetic phenotypic changes, but the relationship between the two types of changes is controversial. Contrary to the view that plastic changes serve as steppingstones to genetic adaptations, recent transcriptome studies reported that genetic gene expression changes more often reverse than reinforce plastic expression changes in experimental evolution. However, it was pointed out that this trend could be an artifact of the statistical nonindependence between the estimates of plastic and genetic phenotypic changes, because both estimates rely on the phenotypic measure at the plastic stage. Using computer simulation, we show that indeed the nonindependence can cause an apparent excess of expression reversion relative to reinforcement. We propose a parametric bootstrap method and show by simulation that it removes the bias almost entirely. Analyzing transcriptome data from a total of 34 parallel lines in 5 experimental evolution studies of Escherichia coli, yeast, and guppies that are amenable to our method confirms that genetic expression changes tend to reverse plastic changes. Thus, at least for gene expression traits, phenotypic plasticity does not generally facilitate genetic adaptation. Several other comparisons of statistically nonindependent estimates are commonly performed in evolutionary genomics such as that between cis- and trans-effects of mutations on gene expression and that between transcriptional and translational effects on gene expression. It is important to validate previous results from such comparisons, and our proposed statistical analyses can be useful for this purpose.
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Adaptación Biológica/genética , Expresión Génica , Modelos Genéticos , Animales , Simulación por Computador , Escherichia coli , Técnicas Genéticas , Poecilia , LevadurasRESUMEN
The originally published HTML version of this Article contained errors in the three equations in the Methods sub-section 'Metabolic network analysis', whereby the Greek letter eta (η) was inadvertently used in place of beta (ß) during the production process. These errors have now been corrected in the HTML version of the Article; the PDF was correct at the time of publication.
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Organismal adaptation to a new environment may start with plastic phenotypic changes followed by genetic changes, but whether the plastic changes are stepping stones to genetic adaptation is debated. Here we address this question by investigating gene expression and metabolic flux changes in the two-phase adaptation process using transcriptomic data from multiple experimental evolution studies and computational metabolic network analysis, respectively. We discover that genetic changes more frequently reverse than reinforce plastic phenotypic changes in virtually every adaptation. Metabolic network analysis reveals that, even in the presence of plasticity, organismal fitness drops after environmental shifts, but largely recovers through subsequent evolution. Such fitness trajectories explain why plastic phenotypic changes are genetically compensated rather than strengthened. In conclusion, although phenotypic plasticity may serve as an emergency response to a new environment that is necessary for survival, it does not generally facilitate genetic adaptation by bringing the organismal phenotype closer to the new optimum.
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Adaptación Biológica , Ambiente , Redes y Vías Metabólicas/genética , Animales , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/fisiología , Perfilación de la Expresión Génica , Fenotipo , Poecilia/genética , Poecilia/metabolismo , Poecilia/fisiología , Transcriptoma , Levaduras/genética , Levaduras/metabolismo , Levaduras/fisiologíaRESUMEN
Although evolution by natural selection is widely regarded as the most important principle of biology, it is unknown whether phenotypic variations within and between species are mostly adaptive or neutral due to the lack of relevant studies of large, unbiased samples of phenotypic traits. Here, we examine 210 yeast morphological traits chosen because of experimental feasibility irrespective of their potential adaptive values. Our analysis is based on the premise that, under neutrality, the rate of phenotypic evolution measured in the unit of mutational size declines as the trait becomes more important to fitness, analogous to the neutral paradigm that functional genes evolve more slowly than functionless pseudogenes. However, we find faster evolution of more important morphological traits within and between species, rejecting the neutral hypothesis. By contrast, an analysis of 3,466 gene expression traits fails to refute neutrality. Thus, at least in yeast, morphological evolution appears largely adaptive, but the same may not apply to other classes of phenotypes. Our neutrality test is applicable to other species, especially genetic model organisms, for which estimations of mutational size and trait importance are relatively straightforward.
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Evolución Biológica , Genes Fúngicos , Modelos Genéticos , Mutación , Fenotipo , Saccharomyces cerevisiae/genética , Adaptación Biológica , Variación Genética , Análisis de Componente Principal , Selección Genética , Factores de TiempoRESUMEN
The budding yeast Saccharomyces cerevisiae is the best studied eukaryote in molecular and cell biology, but its utility for understanding the genetic basis of phenotypic variation in natural populations is limited by inefficient association mapping due to strong and complex population structure. To overcome this challenge, we generated genome sequences for 85 strains and performed a comprehensive population genomic survey of a total of 190 diverse strains. We identified considerable variation in population structure among chromosomes and identified 181 genes that are absent from the reference genome. Many of these nonreference genes are expressed and we functionally confirmed that two of these genes confer increased resistance to antifungals. Next, we simultaneously measured the growth rates of over 4,500 laboratory strains, each of which lacks a nonessential gene, and 81 natural strains across multiple environments using unique DNA barcode present in each strain. By combining the genome-wide reverse genetic information gained from the gene deletion strains with a genome-wide association analysis from the natural strains, we identified genomic regions associated with fitness variation in natural populations. To experimentally validate a subset of these associations, we used reciprocal hemizygosity tests, finding that while the combined forward and reverse genetic approaches can identify a single causal gene, the phenotypic consequences of natural genetic variation often follow a complicated pattern. The resources and approach provided outline an efficient and reliable route to association mapping in yeast and significantly enhance its value as a model for understanding the genetic mechanisms underlying phenotypic variation and evolution in natural populations.
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Aptitud Genética/genética , Genética Inversa/métodos , Saccharomyces cerevisiae/genética , Proliferación Celular/genética , Mapeo Cromosómico/métodos , Variación Genética/genética , Genoma Fúngico/genética , Estudio de Asociación del Genoma Completo/métodos , Genómica , Fenotipo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
Genetic robustness refers to phenotypic invariance in the face of mutation and is a common characteristic of life, but its evolutionary origin is highly controversial. Genetic robustness could be an intrinsic property of biological systems, a result of direct natural selection, or a byproduct of selection for environmental robustness. To differentiate among these hypotheses, we analyze the metabolic network of Escherichia coli and comparable functional random networks. Treating the flux of each reaction as a trait and computationally predicting trait values upon mutations or environmental shifts, we discover that 1) genetic robustness is greater for the actual network than the random networks, 2) the genetic robustness of a trait increases with trait importance and this correlation is stronger in the actual network than in the random networks, and 3) the above result holds even after the control of environmental robustness. These findings demonstrate an adaptive origin of genetic robustness, consistent with the theoretical prediction that, under certain conditions, direct selection is sufficiently powerful to promote genetic robustness in cellular organisms.
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Escherichia coli/genética , Escherichia coli/metabolismo , Evolución Biológica , Simulación por Computador , Ambiente , Evolución Molecular , Análisis de Flujos Metabólicos/métodos , Redes y Vías Metabólicas , Modelos Genéticos , Mutación , Fenotipo , Selección GenéticaRESUMEN
Most phenotypic traits are controlled by many genes, but a global picture of the genotype-phenotype map (GPM) is lacking. For example, in no species do we know generally how many genes affect a trait and how large these effects are. It is also unclear to what extent GPMs are shaped by natural selection. Here we address these fundamental questions using the reverse genetic data of 220 morphological traits in 4,718 budding yeast strains, each of which lacks a nonessential gene. We show that 1) the proportion of genes affecting a trait varies from <1% to >30%, averaging 6%, 2) most traits are impacted by many more small-effect genes than large-effect genes, and 3) the mean effect of all nonessential genes on a trait decreases precipitously as the estimated importance of the trait to fitness increases. An analysis of 3,116 yeast gene expression traits in 754 gene-deletion strains reveals a similar pattern. These findings illustrate the power of genome-wide reverse genetics in genotype-phenotype mapping, uncover an enormous range of genetic complexity of phenotypic traits, and suggest that the GPM of cellular organisms has been shaped by natural selection for mutational robustness.