scholarly journals The Population Genetics of Pleiotropy, and the Evolution of Collateral Resistance and Sensitivity in Bacteria

2020 ◽  
Author(s):  
Sarah M. Ardell ◽  
Sergey Kryazhimskiy
Keyword(s):  
Home Environment ◽  
Fitness Landscape ◽  
Published Data ◽  
Large Uncertainty ◽  
Knock Out ◽  
Adaptive Mutations ◽  
Collateral Sensitivity ◽  
Fitness Effects ◽  
Fitness Tradeoffs ◽  
Measurable Property

AbstractPleiotropic fitness tradeoffs and their opposite, buttressing pleiotropy, underlie many important phenomena in ecology and evolution. Yet, predicting whether a population adapting to one (“home”) environment will concomitantly gain or lose fitness in another (“non-home”) environment remains challenging, especially when adaptive mutations have diverse pleiotropic effects. Here, we address this problem using the concept of the joint distribution of fitness effects (JDFE), a local measurable property of the fitness landscape. We derive simple statistics of the JDFE that predict the expected slope, variance and co-variance of non-home fitness trajectories. We estimate these statistics from published data from the Escherichia coli knock-out collection in the presence of antibiotics. We find that, for some drug pairs, the average trend towards collateral sensitivity may be masked by large uncertainty, even in the absence of epistasis. We provide simple theoretically grounded guidelines for designing robust sequential drug protocols.

scholarly journals Diverse phenotypic and genetic responses to short-term selection in evolving Escherichia coli populations

2015 ◽  
Author(s):  
Marcus M Dillon ◽  
Nicholas P Rouillard ◽  
Brian Van Dam ◽  
Romain Gallet ◽  
Vaughn S Cooper
Keyword(s):  
Escherichia Coli ◽  
Fitness Landscape ◽  
Single Point ◽  
Beneficial Mutations ◽  
True Nature ◽  
Term Selection ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Genetic Responses

Beneficial mutations fuel adaptation by altering phenotypes that enhance the fit of organisms to their environment. However, the phenotypic effects of mutations often depend on ecological context, making the distribution of effects across multiple environments essential to understanding the true nature of beneficial mutations. Studies that address both the genetic basis and ecological consequences of adaptive mutations remain rare. Here, we characterize the direct and pleiotropic fitness effects of a collection of 21 first-step beneficial mutants derived from naive and adapted genotypes used in a long-term experimental evolution of Escherichia coli. Whole-genome sequencing was used to identify most beneficial mutations. In contrast to previous studies, we find diverse fitness effects of mutations selected in a simple environment and few cases of genetic parallelism. The pleiotropic effects of these mutations were predominantly positive but some mutants were highly antagonistic in alternative environments. Further, the fitness effects of mutations derived from the adapted genotypes were dramatically reduced in nearly all environments. These findings suggest that many beneficial variants are accessible from a single point on the fitness landscape, and the fixation of alternative beneficial mutations may have dramatic consequences for niche breadth reduction via metabolic erosion.

Comment on Cameron and Cameron (2002): “Children of Homosexual Parents Report Childhood Difficulties”

2002 ◽  
Vol 91 (1) ◽  
pp. 331-332
Author(s):  
Lowell L. Brubaker
Keyword(s):  
Home Environment ◽  
Psychological Trauma ◽  
Parent Report ◽  
Published Data ◽  
Negative Consequences ◽  
Control Groups ◽  
Childhood Difficulties

Cameron and Cameron's reanalysis of published data in 2002 indicates children being raised in a home environment with at least one homosexual parent report some negative consequences. However, a closer look at the information presented suggests (especially in the absence of control groups) that the negative consequences documented do not constitute major psychological trauma. Rather, they are more in the nature of the teasing and bullying that plagues any child who comes from a home that may be atypical in any fashion.

scholarly journals Adaptive walks on high-dimensional fitness landscapes and seascapes with distance-dependent statistics

2018 ◽  
Author(s):  
Atish Agarwala ◽  
Daniel S. Fisher
Keyword(s):  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Broad Class ◽  
Fitness Landscapes ◽  
High Dimensional ◽  
General Function ◽  
Long Distance ◽  
Future Evolution ◽  
Adaptive Mutations ◽  
Adaptive Walks

AbstractThe dynamics of evolution is intimately shaped by epistasis — interactions between genetic elements which cause the fitness-effect of combinations of mutations to be non-additive. Analyzing evolutionary dynamics that involves large numbers of epistatic mutations is intrinsically difficult. A crucial feature is that the fitness landscape in the vicinity of the current genome depends on the evolutionary history. A key step is thus developing models that enable study of the effects of past evolution on future evolution. In this work, we introduce a broad class of high-dimensional random fitness landscapes for which the correlations between fitnesses of genomes are a general function of genetic distance. Their Gaussian character allows for tractable computational as well as analytic understanding. We study the properties of these landscapes focusing on the simplest evolutionary process: random adaptive (uphill) walks. Conventional measures of “ruggedness” are shown to not much affect such adaptive walks. Instead, the long-distance statistics of epistasis cause all properties to be highly conditional on past evolution, determining the statistics of the local landscape (the distribution of fitness-effects of available mutations and combinations of these), as well as the global geometry of evolutionary trajectories. In order to further explore the effects of conditioning on past evolution, we model the effects of slowly changing environments. At long times, such fitness “seascapes” cause a statistical steady state with highly intermittent evolutionary dynamics: populations undergo bursts of rapid adaptation, interspersed with periods in which adaptive mutations are rare and the population waits for more new directions to be opened up by changes in the environment. Finally, we discuss prospects for studying more complex evolutionary dynamics and on broader classes of high-dimensional landscapes and seascapes.

scholarly journals Reversion is most likely under high mutation supply, when compensatory mutations don’t fully restore fitness costs

2020 ◽  
Author(s):  
Pleuni S. Pennings ◽  
C. Brandon Ogbunugafor ◽  
Ruth Hershberg
Keyword(s):  
Mutation Rate ◽  
Experimental Evolution ◽  
Evolutionary Dynamics ◽  
Microbial Evolution ◽  
Compensatory Mutation ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Theoretical Approaches ◽  
Evolution Study ◽  
Compensatory Mutations

AbstractAdaptive mutations are often associated with a fitness cost. These costs can be compensated for through the acquisition of additional mutations, or the adaptations can be lost through reversion, in settings where they are no longer favored. While the dynamics of adaptation, reversion and compensation have been central features in several studies of microbial evolution, few studies have attempted to resolve the population genetics underlying how and when either compensation or reversion occur. Specifically, questions remain regarding how certain actors—the evolution of mutators and whether compensatory mutations alleviate costs fully or partially—may influence evolutionary dynamics of compensation and reversion. In this study, we attempt to explain findings from an experimental evolution study by utilizing computational and theoretical approaches towards a more refined understanding of how mutation rate and the fitness effects of compensatory mutation influence evolutionary dynamics. We find that high mutation rates increase the probability of reversion of deleterious adaptations when compensation is only partial. The existence of even a single fully compensatory mutation is associated with a dramatically decreased probability of reversion. Experimental results suggest that, in some contexts, compensatory mutations are not able to fully alleviate costs associated with adaption. Our findings emphasize the role of both mutation rate and the fitness effects of compensatory mutation in crafting evolutionary dynamics, and highlight the importance of population genetic theory for explaining findings from experimental evolution.

scholarly journals Evaluating the within-host fitness effects of mutations fixed during virus adaptation to different ecotypes of a new host

2015 ◽  
Vol 370 (1675) ◽  
pp. 20140292 ◽  
Author(s):  
Julia Hillung ◽  
José M. Cuevas ◽  
Santiago F. Elena
Keyword(s):  
Genetic Variation ◽  
Fitness Landscape ◽  
Host Population ◽  
Gene Model ◽  
New Host ◽  
Host Fitness ◽  
Fitness Effects ◽  
Rate Of Spread ◽  
Virus Diversity ◽  
Gene For Gene

The existence of genetic variation for resistance in host populations is assumed to be essential to the spread of an emerging virus. Models predict that the rate of spread slows down with the increasing frequency and higher diversity of resistance alleles in the host population. We have been using the experimental pathosystem Arabidopsis thaliana —tobacco etch potyvirus (TEV) to explore the interplay between genetic variation in host's susceptibility and virus diversity. We have recently shown that TEV populations evolving in A. thaliana ecotypes that differ in susceptibility to infection gained within-host fitness, virulence and infectivity in a manner compatible with a gene-for-gene model of host–parasite interactions: hard-to-infect ecotypes were infected by generalist viruses, whereas easy-to-infect ecotypes were infected by every virus. We characterized the genomes of the evolved viruses and found cases of host-driven convergent mutations. To gain further insights in the mechanistic basis of this gene-for-gene model, we have generated all viral mutations individually as well as in specific combinations and tested their within-host fitness effects across ecotypes. Most of these mutations were deleterious or neutral in their local ecotype and only a very reduced number had a host-specific beneficial effect. We conclude that most of the mutations fixed during the evolution experiment were so by drift or by selective sweeps along with the selected driver mutation. In addition, we evaluated the ruggedness of the underlying adaptive fitness landscape and found that mutational effects were mostly multiplicative, with few cases of significant epistasis.

scholarly journals Inferring Parameters of the Distribution of Fitness Effects of New Mutations When Beneficial Mutations Are Strongly Advantageous and Rare

2020 ◽  
Vol 10 (7) ◽  
pp. 2317-2326 ◽  
Author(s):  
Tom R. Booker
Keyword(s):  
Evolutionary Genetics ◽  
Molecular Data ◽  
Substantial Contribution ◽  
Beneficial Mutations ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Relative Contribution ◽  
Standing Variation ◽  
Accuracy And Precision ◽  
New Mutations

Characterizing the distribution of fitness effects (DFE) for new mutations is central in evolutionary genetics. Analysis of molecular data under the McDonald-Kreitman test has suggested that adaptive substitutions make a substantial contribution to between-species divergence. Methods have been proposed to estimate the parameters of the distribution of fitness effects for positively selected mutations from the unfolded site frequency spectrum (uSFS). Such methods perform well when beneficial mutations are mildly selected and frequent. However, when beneficial mutations are strongly selected and rare, they may make little contribution to standing variation and will thus be difficult to detect from the uSFS. In this study, I analyze uSFS data from simulated populations subject to advantageous mutations with effects on fitness ranging from mildly to strongly beneficial. As expected, frequent, mildly beneficial mutations contribute substantially to standing genetic variation and parameters are accurately recovered from the uSFS. However, when advantageous mutations are strongly selected and rare, there are very few segregating in populations at any one time. Fitting the uSFS in such cases leads to underestimates of the strength of positive selection and may lead researchers to false conclusions regarding the relative contribution adaptive mutations make to molecular evolution. Fortunately, the parameters for the distribution of fitness effects for harmful mutations are estimated with high accuracy and precision. The results from this study suggest that the parameters of positively selected mutations obtained by analysis of the uSFS should be treated with caution and that variability at linked sites should be used in conjunction with standing variability to estimate parameters of the distribution of fitness effects in the future.

scholarly journals The fitness landscape of the codon space across environments

2018 ◽  
Author(s):  
Inès Fragata ◽  
Sebastian Matuszewski ◽  
Mark A. Schmitz ◽  
Thomas Bataillon ◽  
Jeffrey D. Jensen ◽  
...  
Keyword(s):  
Amino Acid ◽  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Fitness Landscapes ◽  
Synonymous Mutations ◽  
Landscape Studies ◽  
Fitness Effects ◽  
Bayesian Monte Carlo ◽  
The Relationship

AbstractFitness landscapes map the relationship between genotypes and fitness. However, most fitness landscape studies ignore the genetic architecture imposed by the codon table and thereby neglect the potential role of synonymous mutations. To quantify the fitness effects of synonymous mutations and their potential impact on adaptation on a fitness landscape, we use a new software based on Bayesian Monte Carlo Markov Chain methods and reestimate selection coefficients of all possible codon mutations across 9 amino-acid positions in Saccharomyces cerevisiae Hsp90 across 6 environments. We quantify the distribution of fitness effects of synonymous mutations and show that it is dominated by many mutations of small or no effect and few mutations of larger effect. We then compare the shape of the codon fitness landscape across amino-acid positions and environments, and quantify how the consideration of synonymous fitness effects changes the evolutionary dynamics on these fitness landscapes. Together these results highlight a possible role of synonymous mutations in adaptation and indicate the potential mis-inference when they are neglected in fitness landscape studies.

scholarly journals Empirical determinants of adaptive mutations in yeast experimental evolution

2015 ◽  
Author(s):  
Celia Payen ◽  
Anna B Sunshine ◽  
Giang T Ong ◽  
Jamie L Pogachar ◽  
Wei Zhao ◽  
...  
Keyword(s):  
Experimental Evolution ◽  
High Throughput Sequencing ◽  
Fitness Landscape ◽  
Genome Structure ◽  
Mutation Spectrum ◽  
Relative Fitness ◽  
Yeast Genome ◽  
Beneficial Mutations ◽  
Adaptive Mutations ◽  
A Genome

High-throughput sequencing technologies have enabled expansion of the scope of genetic screens to identify mutations that underlie quantitative phenotypes, such as fitness improvements that occur during the course of experimental evolution. This new capability has allowed us to describe the relationship between fitness and genotype at a level never possible before, and ask deeper questions, such as how genome structure, available mutation spectrum, and other factors drive evolution. Here we combined functional genomics and experimental evolution to first map on a genome scale the distribution of potential beneficial mutations available as a first step to an evolving population and then compare these to the mutations actually observed in order to define the constraints acting upon evolution. We first constructed a single-step fitness landscape for the yeast genome by using barcoded gene deletion and overexpression collections, competitive growth in continuous culture, and barcode sequencing. By quantifying the relative fitness effects of thousands of single-gene amplifications or deletions simultaneously we revealed the presence of hundreds of accessible evolutionary paths. To determine the actual mutation spectrum used in evolution, we built a catalog of >1000 mutations selected during experimental evolution. By combining both datasets, we were able to ask how and why evolution is constrained. We identified adaptive mutations in laboratory evolved populations, derived mutational signatures in a variety of conditions and ploidy states, and determined that half of the mutations accumulated positively affect cellular fitness. We also uncovered hundreds of potential beneficial mutations never observed in the mutational spectrum derived from the experimental evolution catalog and found that those adaptive mutations become accessible in the absence of the dominant adaptive solution. This comprehensive functional screen explored the set of potential adaptive mutations on one genetic background, and allows us for the first time at this scale to compare the mutational path with the actual, spontaneously derived spectrum of mutations.

scholarly journals Empirical noise-mean fitness landscapes and the evolution of gene expression

2018 ◽  
Author(s):  
Joern M Schmiedel ◽  
Lucas B. Carey ◽  
Ben Lehner
Keyword(s):  
Gene Expression ◽  
Fitness Landscape ◽  
Fitness Landscapes ◽  
Similar Magnitude ◽  
Expression Systems ◽  
Fitness Effects ◽  
Mean Fitness ◽  
Noise In Gene Expression ◽  
Cell Variation ◽  
Magnitude Sensitivity

The effects of cell-to-cell variation (noise) in gene expression have proven difficult to quantify, in part due to the mechanistic coupling of noise to mean expression. To independently evaluate the effects of changes in expression mean and noise we determined the fitness landscapes in mean-noise expression space for 33 genes in yeast. The landscapes can be decomposed into two principal topologies: the fitness effects of protein shortage and surplus. For most genes, the fitness impact of sustained (mean) and short-lived (noise) deviations away from the expression optimum are linked and of similar magnitude. Sensitivity to both protein shortage and surplus creates a fitness landscape in which an epistatic ratchet uncouples the evolution of noise from mean expression, promoting noise minimization. These results demonstrate that noise is detrimental for many genes and reveal non-trivial consequences of mean-noise-fitness topologies for the evolution of gene expression systems.

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