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 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 Adaptation of Escherichia coli to Long-Term Serial Passage in Complex Medium: Evidence of Parallel Evolution

mSystems ◽  
2017 ◽  
Vol 2 (2) ◽  
Author(s):  
Karin E. Kram ◽  
Christopher Geiger ◽  
Wazim Mohammed Ismail ◽  
Heewook Lee ◽  
Haixu Tang ◽  
...  
Keyword(s):  
Experimental Evolution ◽  
Parallel Evolution ◽  
Microbial Evolution ◽  
Complex Medium ◽  
Evolutionary Mechanisms ◽  
Adaptive Mutations ◽  
Experimental Systems ◽  
Experimental Laboratory ◽  
Five Phases

ABSTRACT With a growing body of work directed toward understanding the mechanisms of evolution using experimental systems, it is crucial to decipher what effects the experimental setup has on the outcome. If the goal of experimental laboratory evolution is to elucidate underlying evolutionary mechanisms and trends, these must be demonstrated in a variety of systems and environments. Here, we perform experimental evolution in a complex medium allowing the cells to transition through all five phases of growth, including death phase and long-term stationary phase. We show that the swiftness of selection and the specific targets of adaptive evolution are different in this system compared to others. We also observe parallel evolution where different mutations in the same genes are under positive natural selection. Together, these data show that while some outcomes of microbial evolution experiments may be generalizable, many outcomes will be environment or system specific. Experimental evolution of bacterial populations in the laboratory has led to identification of several themes, including parallel evolution of populations adapting to carbon starvation, heat stress, and pH stress. However, most of these experiments study growth in defined and/or constant environments. We hypothesized that while there would likely continue to be parallelism in more complex and changing environments, there would also be more variation in what types of mutations would benefit the cells. In order to test our hypothesis, we serially passaged Escherichia coli in a complex medium (Luria-Bertani broth) throughout the five phases of bacterial growth. This passaging scheme allowed cells to experience a wide variety of stresses, including nutrient limitation, oxidative stress, and pH variation, and therefore allowed them to adapt to several conditions. After every ~30 generations of growth, for a total of ~300 generations, we compared both the growth phenotypes and genotypes of aged populations to the parent population. After as few as 30 generations, populations exhibit changes in growth phenotype and accumulate potentially adaptive mutations. There were many genes with mutant alleles in different populations, indicating potential parallel evolution. We examined 8 of these alleles by constructing the point mutations in the parental genetic background and competed those cells with the parent population; five of these alleles were found to be adaptive. The variety and swiftness of adaptive mutations arising in the populations indicate that the cells are adapting to a complex set of stresses, while the parallel nature of several of the mutations indicates that this behavior may be generalized to bacterial evolution. IMPORTANCE With a growing body of work directed toward understanding the mechanisms of evolution using experimental systems, it is crucial to decipher what effects the experimental setup has on the outcome. If the goal of experimental laboratory evolution is to elucidate underlying evolutionary mechanisms and trends, these must be demonstrated in a variety of systems and environments. Here, we perform experimental evolution in a complex medium allowing the cells to transition through all five phases of growth, including death phase and long-term stationary phase. We show that the swiftness of selection and the specific targets of adaptive evolution are different in this system compared to others. We also observe parallel evolution where different mutations in the same genes are under positive natural selection. Together, these data show that while some outcomes of microbial evolution experiments may be generalizable, many outcomes will be environment or system specific.

scholarly journals Evolution of mutation rates in rapidly adapting asexual populations

2016 ◽  
Author(s):  
Benjamin H. Good ◽  
Michael M. Desai
Keyword(s):  
Mutation Rate ◽  
Evolutionary Dynamics ◽  
Empirical Work ◽  
Indirect Selection ◽  
Microbial Evolution ◽  
Mutation Rates ◽  
Fixation Probability ◽  
Deleterious Mutations ◽  
Clonal Interference ◽  
Asexual Population

Mutator and antimutator alleles often arise and spread in both natural microbial populations and laboratory evolution experiments. The evolutionary dynamics of these mutation rate modifiers are determined by indirect selection on linked beneficial and deleterious mutations. These indirect selection pressures have been the focus of much earlier theoretical and empirical work, but we still have a limited analytical understanding of how the interplay between hitchhiking and deleterious load influences the fates of modifier alleles. Our understanding is particularly limited when clonal interference is common, which is the regime of primary interest in laboratory microbial evolution experiments. Here, we calculate the fixation probability of a mutator or antimutator allele in a rapidly adapting asexual population, and we show how this quantity depends on the population size, the beneficial and deleterious mutation rates, and the strength of a typical driver mutation. In the absence of deleterious mutations, we find that clonal interference enhances the fixation probability of mutators, even as they provide a diminishing benefit to the overall rate of adaptation. When deleterious mutations are included, natural selection pushes the population towards a stable mutation rate that can be suboptimal for the adaptation of the population as a whole. The approach to this stable mutation rate is not necessarily monotonic, and selection can favor mutator and antimutator alleles that overshoot the stable mutation rate by substantial amounts.

scholarly journals Early adaptation in a microbial community is dominated by mutualism-enhancing mutations

2021 ◽  
Author(s):  
Sandeep Venkataram ◽  
Huan-Yu Kuo ◽  
Erik F. Y. Hom ◽  
Sergey Kryazhimskiy
Keyword(s):  
Species Interactions ◽  
Evolutionary Dynamics ◽  
Ecological Communities ◽  
Ecological Interactions ◽  
Biological Organization ◽  
Adaptive Mutations ◽  
Fitness Effects ◽  
Multiple Levels ◽  
Lineage Tracking ◽  
Different Levels

Evolutionary dynamics in ecological communities are often repeatable, but how species interactions affect the distribution of evolutionary outcomes at different levels of biological organization is unclear. Here, we use barcode lineage tracking to experimentally address this gap in a facultatively mutualistic community formed by the alga Chlamydomonas reinhardtii and the yeast Saccharomyces cerevisiae. We find that interactions with the alga alter the magnitude but not the sign of the fitness effects of adaptive mutations in yeast, changing the distribution of mutants contending for fixation. In the presence of alga, most contending mutants reinforce the mutualism and make evolution more repeatable at the community level. Thus, ecological interactions not only alter the trajectory of evolution but also dictate its repeatability at multiple levels of biological organization.

scholarly journals Effect of mutation supply on population dynamics and trait evolution in experimental microbial community

2021 ◽  
Author(s):  
Johannes Cairns ◽  
Alexandre Jousset ◽  
Lutz Becks ◽  
Teppo Hiltunen
Keyword(s):  
Population Dynamics ◽  
Population Size ◽  
Mutation Rate ◽  
Species Interactions ◽  
Community Dynamics ◽  
Evolutionary Dynamics ◽  
Serial Passage ◽  
Trait Evolution ◽  
Adaptive Mutations ◽  
High Resource

Mutation supply can influence eco-evolutionary dynamics in important ways which have received little attention. Mutation supply determines key features of population genetics, such as the pool of adaptive mutations, evolutionary pathways available, and importance of processes such as clonal interference. The resultant trait evolutionary dynamics, in turn, can alter population size and species interactions. However, controlled experiments testing for the importance of mutation supply on rapid adaptation and thereby population and community dynamics are lacking. To close this knowledge gap, we performed a serial passage experiment with wild-type Pseudomonas fluorescens and an isogenic xerD mutant with reduced mutation rate. Bacteria were grown at two resource levels in combination with the presence of a ciliate predator. We found that a higher mutation supply enabled faster adaptation to the low-resource environment and anti-predatory defense. This was associated with higher population size at the ecological level and better access to high-recurrence mutational targets at the genomic level for the strain with higher mutation supply. In contrast, mutation rate did not affect growth under high-resource level, possibly because of more permissive conditions or high population size saturated in mutations. Our results demonstrate that intrinsic mutation rate influences population dynamics and trait evolution particularly when population size is constrained by extrinsic conditions.

scholarly journals Somatic deficiency causes reproductive parasitism in a fungus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexey A. Grum-Grzhimaylo ◽  
Eric Bastiaans ◽  
Joost van den Heuvel ◽  
Cristina Berenguer Millanes ◽  
Alfons J. M. Debets ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Experimental Evolution ◽  
Evolutionary Dynamics ◽  
Genetic Load ◽  
Wild Type ◽  
Fusion Frequency ◽  
Somatic Fusion ◽  
Extensive Variation ◽  
Reproductive Parasitism ◽  
Multicellular Organisms

AbstractSome multicellular organisms can fuse because mergers potentially provide mutual benefits. However, experimental evolution in the fungus Neurospora crassa has demonstrated that free fusion of mycelia favours cheater lineages, but the mechanism and evolutionary dynamics of this exploitation are unknown. Here we show, paradoxically, that all convergently evolved cheater lineages have similar fusion deficiencies. These mutants are unable to initiate fusion but retain access to wild-type mycelia that fuse with them. This asymmetry reduces cheater-mutant contributions to somatic substrate-bound hyphal networks, but increases representation of their nuclei in the aerial reproductive hyphae. Cheaters only benefit when relatively rare and likely impose genetic load reminiscent of germline senescence. We show that the consequences of somatic fusion can be unequally distributed among fusion partners, with the passive non-fusing partner profiting more. We discuss how our findings may relate to the extensive variation in fusion frequency of fungi found in nature.

scholarly journals Changes in the distribution of fitness effects and adaptive mutational spectra following a single first step towards adaptation

2020 ◽  
Author(s):  
Dimitra Aggeli ◽  
Yuping Li ◽  
Gavin Sherlock
Keyword(s):  
Evolutionary Dynamics ◽  
Common Ancestor ◽  
Single Point ◽  
Relative Fitness ◽  
Single Point Mutation ◽  
Historical Contingency ◽  
Mutational Spectra ◽  
Fitness Effects ◽  
Mutational Step ◽  
Diminishing Returns

AbstractThe fitness effects of random mutations are contingent upon the genetic and environmental contexts in which they occur, and this contributes to the unpredictability of evolutionary outcomes at the molecular level. Despite this unpredictability, the rate of adaptation in homogeneous environments tends to decrease over evolutionary time, due to diminishing returns epistasis, causing relative fitness gains to be predictable over the long term. Here, we studied the extent of diminishing returns epistasis and the changes in the adaptive mutational spectra after yeast populations have already taken their first adaptive mutational step. We used three distinct adaptive clones that arose under identical conditions from a common ancestor, from which they diverge by a single point mutation, to found populations that we further evolved. We followed the evolutionary dynamics of these populations by lineage tracking and determined adaptive outcomes using fitness assays and whole genome sequencing. We found compelling evidence for diminishing returns: fitness gains during the 2nd step of adaptation are smaller than those of the 1st step, due to a compressed distribution of fitness effects in the 2nd step. We also found strong evidence for historical contingency at the genic level: the beneficial mutational spectra of the 2nd-step adapted genotypes differ with respect to their ancestor and to each other, despite the fact that the three founders’ 1st-step mutations provided their fitness gains due to similar phenotypic improvements. While some targets of selection in the second step are shared with those seen in the common ancestor, other targets appear to be contingent on the specific first step mutation, with more phenotypically similar founding clones having more similar adaptive mutational spectra. Finally, we found that disruptive mutations, such as nonsense and frameshift, were much more common in the first step of adaptation, contributing an additional way that both diminishing returns and historical contingency are evident during 2nd step adaptation.

scholarly journals Maximum likelihood estimation of fitness components in experimental evolution

2018 ◽  
Author(s):  
Jingxian Liu ◽  
Jackson Champer ◽  
Chen Liu ◽  
Joan Chung ◽  
Riona Reeves ◽  
...  
Keyword(s):  
Maximum Likelihood ◽  
Experimental Evolution ◽  
Evolutionary Dynamics ◽  
Likelihood Estimation ◽  
Loss Of Function ◽  
Wild Type ◽  
Fitness Components ◽  
Linked Gene ◽  
Males And Females

AbstractEstimating fitness differences between allelic variants is a central goal of experimental evolution. Current methods for inferring selection from allele frequency time series typically assume that evolutionary dynamics at the locus of interest can be described by a fixed selection coefficient. However, fitness is an aggregate of several components including mating success, fecundity, and viability, and distinguishing between these components could be critical in many scenarios. Here we develop a flexible maximum likelihood framework that can disentangle different components of fitness and estimate them individually in males and females from genotype frequency data. As a proof-of-principle, we apply our method to experimentally-evolved cage populations of Drosophila melanogaster, in which we tracked the relative frequencies of a loss-of-function and wild-type allele of yellow. This X-linked gene produces a recessive yellow phenotype when disrupted and is involved in male courtship ability. We find that the fitness costs of the yellow phenotype take the form of substantially reduced mating preference of wild-type females for yellow males, together with a modest reduction in the viability of yellow males and females. Our framework should be generally applicable to situations where it is important to quantify fitness components of specific genetic variants, including quantitative characterization of the population dynamics of CRISPR gene drives.

scholarly journals Inactivation of Genes by Frameshift Mutations Provides Rapid Adaptation of an Attenuated Vaccinia Virus

2020 ◽  
Vol 94 (18) ◽  
Author(s):  
Tatiana G. Senkevich ◽  
Erik K. Zhivkoplias ◽  
Andrea S. Weisberg ◽  
Bernard Moss
Keyword(s):  
Vaccinia Virus ◽  
Experimental Evolution ◽  
Copy Number ◽  
Gene Copy Number ◽  
Myxoma Virus ◽  
Host Cells ◽  
Gene Copy ◽  
Frameshift Mutations ◽  
Adaptive Mutations ◽  
Rapid Acquisition

ABSTRACT Unlike RNA viruses, most DNA viruses replicate their genomes with high-fidelity polymerases that rarely make base substitution errors. Nevertheless, experimental evolution studies have revealed rapid acquisition of adaptive mutations during serial passage of attenuated vaccinia virus (VACV). One way in which adaptation can occur is by an accordion mechanism in which the gene copy number increases followed by base substitutions and, finally, contraction of the gene copy number. Here, we show rapid acquisition of multiple adaptive mutations mediated by a gene-inactivating frameshift mechanism during passage of an attenuated VACV. Attenuation had been achieved by exchanging the VACV A8R intermediate transcription factor gene with the myxoma virus ortholog. A total of seven mutations in six different genes occurred in three parallel passages of the attenuated virus. The most frequent mutations were single-nucleotide insertions or deletions within runs of five to seven As or Ts, although a deletion of 11 nucleotides also occurred, leading to frameshifts and premature stop codons. During 10 passage rounds, the attenuated VACV was replaced by the mutant viruses. At the end of the experiment, virtually all remaining viruses had one fixed mutation and one or more additional mutations. Although nucleotide substitutions in the transcription apparatus accounted for two low-frequency mutations, frameshifts in genes encoding protein components of the mature virion, namely, A26L, G6R, and A14.5L, achieved 74% to 98% fixation. The adaptive role of the mutations was confirmed by making recombinant VACV with A26L or G6R or both deleted, which increased virus replication levels and decreased particle/PFU ratios. IMPORTANCE Gene inactivation is considered to be an important driver of orthopoxvirus evolution. Whereas cowpox virus contains intact orthologs of genes present in each orthopoxvirus species, numerous genes are inactivated in all other members of the genus. Inactivation of additional genes can occur upon extensive passaging of orthopoxviruses in cell culture leading to attenuation in vivo, a strategy for making vaccines. Whether inactivation of multiple viral genes enhances replication in the host cells or has a neutral effect is unknown in most cases. Using an experimental evolution protocol involving serial passages of an attenuated vaccinia virus, rapid acquisition of inactivating frameshift mutations occurred. After only 10 passage rounds, the starting attenuated vaccinia virus was displaced by viruses with one fixed mutation and one or more additional mutations. The high frequency of multiple inactivating mutations during experimental evolution simulates their acquisition during normal evolution and extensive virus passaging to make vaccine strains.

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