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 Evolutionary dynamics and structural consequences of de novo beneficial mutations and mutant lineages arising in a constant environment

BMC Biology ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Margie Kinnersley ◽  
Katja Schwartz ◽  
Dong-Dong Yang ◽  
Gavin Sherlock ◽  
Frank Rosenzweig
Keyword(s):  
High Frequency ◽  
High Throughput Sequencing ◽  
Evolutionary Dynamics ◽  
De Novo ◽  
Allelic Diversity ◽  
Microbial Evolution ◽  
De Novo Mutations ◽  
Beneficial Mutations ◽  
Adaptive Mutations ◽  
The Impact

Abstract Background Microbial evolution experiments can be used to study the tempo and dynamics of evolutionary change in asexual populations, founded from single clones and growing into large populations with multiple clonal lineages. High-throughput sequencing can be used to catalog de novo mutations as potential targets of selection, determine in which lineages they arise, and track the fates of those lineages. Here, we describe a long-term experimental evolution study to identify targets of selection and to determine when, where, and how often those targets are hit. Results We experimentally evolved replicate Escherichia coli populations that originated from a mutator/nonsense suppressor ancestor under glucose limitation for between 300 and 500 generations. Whole-genome, whole-population sequencing enabled us to catalog 3346 de novo mutations that reached > 1% frequency. We sequenced the genomes of 96 clones from each population when allelic diversity was greatest in order to establish whether mutations were in the same or different lineages and to depict lineage dynamics. Operon-specific mutations that enhance glucose uptake were the first to rise to high frequency, followed by global regulatory mutations. Mutations related to energy conservation, membrane biogenesis, and mitigating the impact of nonsense mutations, both ancestral and derived, arose later. New alleles were confined to relatively few loci, with many instances of identical mutations arising independently in multiple lineages, among and within replicate populations. However, most never exceeded 10% in frequency and were at a lower frequency at the end of the experiment than at their maxima, indicating clonal interference. Many alleles mapped to key structures within the proteins that they mutated, providing insight into their functional consequences. Conclusions Overall, we find that when mutational input is increased by an ancestral defect in DNA repair, the spectrum of high-frequency beneficial mutations in a simple, constant resource-limited environment is narrow, resulting in extreme parallelism where many adaptive mutations arise but few ever go to fixation.

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.

scholarly journals Following the Trail of One Million Genomes: Footprints of SARS-CoV-2 Adaptation to Humans

2021 ◽  
Author(s):  
Saymon Akther ◽  
Edgaras Bezrucenkovas ◽  
Li Li ◽  
Brian Sulkow ◽  
Lia Di ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Immune Escape ◽  
Local Level ◽  
Genome Structure ◽  
Base Substitution ◽  
Human Populations ◽  
Clonal Interference ◽  
Adaptive Mutations ◽  
Genome Wide ◽  
A Genome

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has accumulated genomic mutations at an approximately linear rate since it first infected human populations in late 2019. Controversies remain regarding the identity, proportion, and effects of adaptive mutations as SARS-CoV-2 evolves from a bat- to a human-adapted virus. The potential for vaccine-escape mutations poses additional challenges in pandemic control. Despite being of great interest to therapeutic and vaccine development, human-adaptive mutations in SARS-CoV-2 are masked by a genome-wide linkage disequilibrium under which neutral and even deleterious mutations can reach fixation by chance or through hitchhiking. Furthermore, genome-wide linkage equilibrium imposes clonal interference by which multiple adaptive mutations compete against one another. Informed by insights from microbial experimental evolution, we analyzed close to one million SARS-CoV-2 genomes sequenced during the first year of the COVID-19 pandemic and identified putative human-adaptive mutations according to the rates of synonymous and missense mutations, temporal linkage, and mutation recurrence. Furthermore, we developed a forward-evolution simulator with the realistic SARS-CoV-2 genome structure and base substitution probabilities able to predict viral genome diversity under neutral, background selection, and adaptive evolutionary models. We conclude that adaptive mutations have emerged early, rapidly, and constantly to dominate SARS-CoV-2 populations despite clonal interference and purifying selection. Our analysis underscores a need for genomic surveillance of mutation trajectories at the local level for early detection of adaptive and immune-escape variants. Putative human-adaptive mutations are over-represented in viral proteins interfering host immunity and binding host-cell receptors and thus may serve as priority targets for designing therapeutics and vaccines against human-adapted forms of SARS-CoV-2.

scholarly journals Adaptive mutations in RNA polymerase and the transcriptional terminator Rho have similar effects onEscherichia coligene expression

2016 ◽  
Author(s):  
Andrea González-González ◽  
Shaun M. Hug ◽  
Alejandra Rodríguez-Verdugo ◽  
Jagdish Suresh Patel ◽  
Brandon S. Gaut
Keyword(s):  
Gene Expression ◽  
Rna Polymerase ◽  
Large Scale ◽  
Relative Fitness ◽  
Detectable Effect ◽  
Gene Encoding ◽  
Transcriptional Terminator ◽  
Beneficial Mutations ◽  
Adaptive Mutations ◽  
Transcriptional Termination

ABSTRACTModifications to transcriptional regulators play a major role in adaptation. Here we compared the effects of multiple beneficial mutations within and betweenEscherichia coli rpoB, the gene encoding the RNA polymerase β subunit, andrho, which encodes a transcriptional terminator. These two genes have harbored adaptive mutations in numerousE. colievolution experiments but particularly in our previous large-scale thermal stress experiment, where the two genes characterized two alternative adaptive pathways. To compare the effects of beneficial mutations, we engineered four advantageous mutations into each of the two genes and measured their effects on fitness, growth, gene expression and transcriptional termination at 42.2°C. Among the eight mutations, tworhomutations had no detectable effect on relative fitness, suggesting they were beneficial only in the context of epistatic interactions. The remaining six mutations had an average relative fitness benefit of ∼20%. TherpoBmutations altered the expression of ∼1700 genes;rhomutations altered the expression of fewer genes, most of which were a subset of the genes altered byrpoB. Across our eight mutants, relative fitness correlated with the degree to which a mutation restored gene expression back to the unstressed, 37.0°C state. Therhomutations do not enhance transcriptional termination in knownrho-terminated regions, but the genome-wide effects of mutations in both genes was to enhance termination. Although beneficial mutations in the two genes did not have identical effects on fitness, growth or gene expression, they acted predominantly through parallel phenotypic effects on gene expression and transcriptional termination.

scholarly journals Reciprocal Sign Epistasis between Frequently Experimentally Evolved Adaptive Mutations Causes a Rugged Fitness Landscape

PLoS Genetics ◽  
2011 ◽  
Vol 7 (4) ◽  
pp. e1002056 ◽  
Author(s):  
Daniel J. Kvitek ◽  
Gavin Sherlock
Keyword(s):  
Fitness Landscape ◽  
Adaptive Mutations

scholarly journals Genetic variance in fitness and its cross-sex covariance predict adaptation during experimental evolution

2020 ◽  
Author(s):  
Eva L. Koch ◽  
Sonja H. Sbilordo ◽  
Frédéric Guillaume
Keyword(s):  
Experimental Evolution ◽  
Genetic Variance ◽  
Environmental Changes ◽  
Additive Genetic Variance ◽  
Relative Fitness ◽  
Male Fitness ◽  
Adaptive Potential ◽  
Genetic Covariance ◽  
Flour Beetles ◽  
Single Stress

AbstractIn presence of rapid environmental changes, it is of particular importance to assess the adaptive potential of populations, which is mostly determined by the additive genetic variation (VA) in fitness. In this study we used Tribolium castaneum (red flour beetles) to investigate its adaptive potential in three new environmental conditions (Dry, Hot, Hot-Dry). We tested for potential constraints that might limit adaptation, including negative genetic covariance between female and male fitness. Based on VA estimates for fitness, we expected the highest relative fitness increase in the most stressful condition Hot-Dry and similar increases in single stress conditions Dry and Hot. High adaptive potential in females in Hot was reduced by a negative covariance with male fitness. We tested adaptation to the three conditions after 20 generations of experimental evolution and found that observed adaptation mainly matched our predictions. Given that body size is commonly used as a proxy for fitness, we also tested how this trait and its genetic variance (including non-additive genetic variance) were impacted by environmental stress. In both traits, variances were sex and condition dependent, but they differed in their variance composition, cross-sex and cross-environment genetic covariances, as well as in the environmental impact on VA.

scholarly journals Detection and application of genome-wide variations in peach for association and genetic relationship analysis

BMC Genetics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Liping Guan ◽  
Ke Cao ◽  
Yong Li ◽  
Jian Guo ◽  
Qiang Xu ◽  
...  
Keyword(s):  
Genetic Relationship ◽  
Dna Markers ◽  
High Throughput Sequencing ◽  
Prunus Persica ◽  
Genetic Research ◽  
Diploid Species ◽  
Sequencing Data ◽  
Relationship Analysis ◽  
Genome Wide ◽  
A Genome

Abstract Background Peach (Prunus persica L.) is a diploid species and model plant of the Rosaceae family. In the past decade, significant progress has been made in peach genetic research via DNA markers, but the number of these markers remains limited. Results In this study, we performed a genome-wide DNA markers detection based on sequencing data of six distantly related peach accessions. A total of 650,693~1,053,547 single nucleotide polymorphisms (SNPs), 114,227~178,968 small insertion/deletions (InDels), 8386~12,298 structure variants (SVs), 2111~2581 copy number variants (CNVs) and 229,357~346,940 simple sequence repeats (SSRs) were detected and annotated. To demonstrate the application of DNA markers, 944 SNPs were filtered for association study of fruit ripening time and 15 highly polymorphic SSRs were selected to analyze the genetic relationship among 221 accessions. Conclusions The results showed that the use of high-throughput sequencing to develop DNA markers is fast and effective. Comprehensive identification of DNA markers, including SVs and SSRs, would be of benefit to genetic diversity evaluation, genetic mapping, and molecular breeding of peach.

scholarly journals A genome-wide identification, characterization and functional analysis of salt-related long non-coding RNAs in non-model plant Pistacia vera L. using transcriptome high throughput sequencing

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Masoomeh Jannesar ◽  
Seyed Mahdi Seyedi ◽  
Maryam Moazzam Jazi ◽  
Vahid Niknam ◽  
Hassan Ebrahimzadeh ◽  
...  
Keyword(s):  
Functional Analysis ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Pistacia Vera ◽  
Model Plant ◽  
Genome Wide ◽  
A Genome ◽  
Non Coding Rnas

scholarly journals Constructing a Reference Genome in a Single Lab: The Possibility to Use Oxford Nanopore Technology

Plants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 270 ◽  
Author(s):  
Yun Gyeong Lee ◽  
Sang Chul Choi ◽  
Yuna Kang ◽  
Kyeong Min Kim ◽  
Chon-Sik Kang ◽  
...  
Keyword(s):  
Plant Species ◽  
Genome Sequencing ◽  
Reference Genome ◽  
Genome Structure ◽  
Plant Genome ◽  
Sequence Information ◽  
Sequencing Analysis ◽  
Oxford Nanopore ◽  
A Genome ◽  
Long Read

The whole genome sequencing (WGS) has become a crucial tool in understanding genome structure and genetic variation. The MinION sequencing of Oxford Nanopore Technologies (ONT) is an excellent approach for performing WGS and it has advantages in comparison with other Next-Generation Sequencing (NGS): It is relatively inexpensive, portable, has simple library preparation, can be monitored in real-time, and has no theoretical limits on reading length. Sorghum bicolor (L.) Moench is diploid (2n = 2x = 20) with a genome size of about 730 Mb, and its genome sequence information is released in the Phytozome database. Therefore, sorghum can be used as a good reference. However, plant species have complex and large genomes when compared to animals or microorganisms. As a result, complete genome sequencing is difficult for plant species. MinION sequencing that produces long-reads can be an excellent tool for overcoming the weak assembly of short-reads generated from NGS by minimizing the generation of gaps or covering the repetitive sequence that appears on the plant genome. Here, we conducted the genome sequencing for S. bicolor cv. BTx623 while using the MinION platform and obtained 895,678 reads and 17.9 gigabytes (Gb) (ca. 25× coverage of reference) from long-read sequence data. A total of 6124 contigs (covering 45.9%) were generated from Canu, and a total of 2661 contigs (covering 50%) were generated from Minimap and Miniasm with a Racon through a de novo assembly using two different tools and mapped assembled contigs against the sorghum reference genome. Our results provide an optimal series of long-read sequencing analysis for plant species while using the MinION platform and a clue to determine the total sequencing scale for optimal coverage that is based on various genome sizes.

scholarly journals Evolutionary stalling and a limit on the power of natural selection to improve a cellular module

2020 ◽  
Vol 117 (31) ◽  
pp. 18582-18590 ◽  
Author(s):  
Sandeep Venkataram ◽  
Ross Monasky ◽  
Shohreh H. Sikaroodi ◽  
Sergey Kryazhimskiy ◽  
Betul Kacar
Keyword(s):  
Escherichia Coli ◽  
Natural Selection ◽  
Adaptive Evolution ◽  
Genetic Load ◽  
Performance Theory ◽  
Biological Functions ◽  
Beneficial Mutations ◽  
Translation Machinery ◽  
Adaptive Mutations ◽  
Organismal Fitness

Cells consist of molecular modules which perform vital biological functions. Cellular modules are key units of adaptive evolution because organismal fitness depends on their performance. Theory shows that in rapidly evolving populations, such as those of many microbes, adaptation is driven primarily by common beneficial mutations with large effects, while other mutations behave as if they are effectively neutral. As a consequence, if a module can be improved only by rare and/or weak beneficial mutations, its adaptive evolution would stall. However, such evolutionary stalling has not been empirically demonstrated, and it is unclear to what extent stalling may limit the power of natural selection to improve modules. Here we empirically characterize how natural selection improves the translation machinery (TM), an essential cellular module. We experimentally evolved populations ofEscherichia coliwith genetically perturbed TMs for 1,000 generations. Populations with severe TM defects initially adapted via mutations in the TM, but TM adaptation stalled within about 300 generations. We estimate that the genetic load in our populations incurred by residual TM defects ranges from 0.5 to 19%. Finally, we found evidence that both epistasis and the depletion of the pool of beneficial mutations contributed to evolutionary stalling. Our results suggest that cellular modules may not be fully optimized by natural selection despite the availability of adaptive mutations.

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