scholarly journals Evolutionary dynamics of asexual hypermutators adapting to a novel environment

2021 ◽  
Author(s):  
Wei-Chin Ho ◽  
Megan G. Behringer ◽  
Samuel F. Miller ◽  
Jadon Gonzales ◽  
Amber Nguyen ◽  
...  
Keyword(s):  
Adaptive Evolution ◽  
Evolutionary Biology ◽  
Evolutionary Dynamics ◽  
Fold Increase ◽  
Luria Bertani ◽  
Mutation Rates ◽  
Wild Type ◽  
Novel Environment ◽  
Luria Bertani Broth ◽  
Nucleotide Mutation

How microbes adapt to a novel environment is a central question in evolutionary biology. While 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 the effects of genetic draft under strong linkage. Despite these linkage effects, the evolved populations exhibit parallelism in fixed mutations, including those potentially related to biofilm formation, transcription regulation, and mutation-rate evolution. Together, these results generally negate the presumed relationship between high mutation rates and high adaptive speed of evolution, providing insight into how clonal adaptation occurs in novel environments.

scholarly journals Fitness landscape analysis reveals that the wild type allele is sub-optimal and mutationally robust

2021 ◽  
Author(s):  
Tzahi Gabzi ◽  
Yitzhak Tzachi Pilpel ◽  
Tamar Friedlander
Keyword(s):  
Mutation Rate ◽  
Evolutionary Biology ◽  
Evolutionary Dynamics ◽  
Fitness Landscape ◽  
Mutation Rates ◽  
Wild Type Allele ◽  
Wild Type ◽  
Type Allele ◽  
Landscape Mapping ◽  
Evolutionary Trajectories

Fitness landscape mapping and the prediction of evolutionary trajectories on these landscapes are major tasks in evolutionary biology research. Evolutionary dynamics is tightly linked to the landscape topography, but this relation is not straightforward. Models predict different evolutionary outcomes depending on mutation rates: high-fitness genotypes should dominate the population under low mutation rates and lower-fitness, mutationally robust (also called 'flat') genotypes - at higher mutation rates. Yet, so far, flat genotypes have been demonstrated in very few cases, particularly in viruses. The quantitative conditions for their emergence were studied only in simplified single-locus, two-peak landscapes. In particular, it is unclear whether within the same genome some genes can be flat while the remaining ones are fit. Here, we analyze a previously measured fitness landscape of a yeast tRNA gene. We found that the wild type allele is sub-optimal, but is mutationally robust ('flat'). Using computer simulations, we estimated the critical mutation rate in which transition from fit to flat allele should occur for a gene with such characteristics. We then used a scaling argument to extrapolate this critical mutation rate for a full genome, assuming the same mutation rate for all genes. Finally, we propose that while the majority of genes are still selected to be fittest, there are a few mutation hot-spots like the tRNA, for which the mutationally robust flat allele is favored by selection.

scholarly journals Quantifying Microsatellite Mutation Rates from Intestinal Stem Cell Dynamics in Msh2-Deficient Murine Epithelium

Genetics ◽  
2019 ◽  
Vol 212 (3) ◽  
pp. 655-665 ◽  
Author(s):  
Joseph Christopher ◽  
Ann-Sofie Thorsen ◽  
Sam Abujudeh ◽  
Filipe C. Lourenço ◽  
Richard Kemp ◽  
...  
Keyword(s):  
Stem Cell ◽  
Fold Increase ◽  
Mutation Rates ◽  
Wild Type ◽  
Cell Dynamics ◽  
Tissue Samples ◽  
Age Related ◽  
Increased Risk ◽  
Microsatellite Mutation ◽  
Risk Of Cancer

Microsatellite sequences have an enhanced susceptibility to mutation, and can act as sentinels indicating elevated mutation rates and increased risk of cancer. The probability of mutant fixation within the intestinal epithelium is dictated by a combination of stem cell dynamics and mutation rate. Here, we exploit this relationship to infer microsatellite mutation rates. First a sensitive, multiplexed, and quantitative method for detecting somatic changes in microsatellite length was developed that allowed the parallel detection of mutant [CA]n sequences from hundreds of low-input tissue samples at up to 14 loci. The method was applied to colonic crypts in Mus musculus, and enabled detection of mutant subclones down to 20% of the cellularity of the crypt (∼50 of 250 cells). By quantifying age-related increases in clone frequencies for multiple loci, microsatellite mutation rates in wild-type and Msh2-deficient epithelium were established. An average 388-fold increase in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 × 10−2) compared to wild-type epithelium (6.2 × 10−5).

scholarly journals Epigenetically Inherited Mutation Rates Predicted to Maximize Adaptation Rates

2021 ◽  
Author(s):  
Yoav Ram ◽  
Yitzhak Tzachi Pilpel ◽  
Gabriela Aleksandra Lobinska
Keyword(s):  
Mutation Rate ◽  
Adaptive Evolution ◽  
Evolutionary Dynamics ◽  
Epigenetic Inheritance ◽  
Fitness Landscapes ◽  
Mutation Rates ◽  
Switching Rate ◽  
Asexual Population ◽  
Parental Phenotype ◽  
Rugged Fitness Landscapes

The mutation rate is an important determinant of evolutionary dynamics. Because the mutation rate determines the rate of appearance of beneficial and deleterious mutations, it is subject to second-order selection. The mutation rate varies between and within species and populations, increases under stress, and is genetically controlled by mutator alleles. The mutation rate may also vary among genetically identical individuals: empirical evidence from bacteria suggests that the mutation rate may be affected by translation errors and expression noise in various proteins (1). Importantly, this non-genetic variation may be heritable via transgenerational epigenetic inheritance. Here we investigate how the inheritance mode of the mutation rate affects the rate of adaptive evolution on rugged fitness landscapes. We model an asexual population with two mutation rate phenotypes, non-mutator and mutator. An offspring may switch from its parental phenotype to the other phenotype. The rate of switching between the mutation rate phenotypes is allowed to span a range of values. Thus, the mutation rate can be interpreted as a genetically inherited trait when the switching rate is low, as an epigenetically inherited trait when the switching rate is intermediate, or as a randomly determined trait when the switching rate is high. We find that epigenetically inherited mutation rates result in the highest rates of adaptation on rugged fitness landscapes for most realistic parameter sets. This is because an intermediate switching rate can maintain the association between a mutator phenotype and pre-existing mutations, which facilitates the crossing of fitness valleys. Our results provide a rationale for the evolution of epigenetic inheritance of the mutation rate, suggesting that it could have been selected because it facilitates adaptive evolution.

scholarly journals Salmonella-Induced Cell Death Is Not Required for Enteritis in Calves

2001 ◽  
Vol 69 (7) ◽  
pp. 4610-4617 ◽  
Author(s):  
Renato L. Santos ◽  
Renée M. Tsolis ◽  
Shuping Zhang ◽  
Thomas A. Ficht ◽  
Andreas J. Bäumler ◽  
...  
Keyword(s):  
Cell Death ◽  
Inflammatory Response ◽  
Fluid Secretion ◽  
Luria Bertani ◽  
Wild Type ◽  
Fluid Accumulation ◽  
Luria Bertani Broth ◽  
Serovar Typhimurium ◽  
In The Wild

ABSTRACT Salmonella enterica serovar Typhimurium causes cell death in bovine monocyte-derived and murine macrophages in vitro by asipB-dependent mechanism. During this process, SipB binds and activates caspase-1, which in turn activates the proinflammatory cytokine interleukin-1β through cleavage. We used bovine ileal ligated loops to address the role of serovar Typhimurium-induced cell death in induction of fluid accumulation and inflammation in this diarrhea model. Twelve perinatal calves had 6- to 9-cm loops prepared in the terminal ileum. They were divided into three groups: one group received an intralumen injection of Luria-Bertani broth as a control in 12 loops. The other two groups (four calves each) were inoculated with 0.75 × 109 CFU of either wild-type serovar Typhimurium (strain IR715) or a sopB mutant per loop in 12 loops. Hematoxylin and eosin-stained sections were scored for inflammation, and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL)-positive cells were detected in situ. Fluid accumulation began at 3 h postinfection (PI). Inflammation was detected in all infected loops at 1 h PI. The area of TUNEL-labeled cells in the wild-type infected loops was significantly higher than that of the controls at 12 h PI, when a severe inflammatory response and tissue damage had already developed. ThesopB mutant induced the same amount of TUNEL-positive cells as the wild type, but it was attenuated for induction of fluid secretion and inflammation. Our results indicate that serovar Typhimurium-induced cell death is not required to trigger an early inflammatory response and fluid accumulation in the ileum.

scholarly journals Human mismatch-repair protein MutL homologue 1 (MLH1) interacts with Escherichia coli MutL and MutS in vivo and in vitro: a simple genetic system to assay MLH1 function

2003 ◽  
Vol 371 (1) ◽  
pp. 183-189 ◽  
Author(s):  
Barbara QUARESIMA ◽  
Pietro ALIFANO ◽  
Pierfrancesco TASSONE ◽  
Enrico V. AVVEDIMENTO ◽  
Francesco S. COSTANZO ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Fold Increase ◽  
Genetic System ◽  
Mutation Rates ◽  
Wild Type ◽  
Mismatched Dna ◽  
Repair Protein

A simple genetic system has been developed to test the effect of over-expression of wild-type or mutated human MutL homologue 1 (hMLH1) proteins on methyl-directed mismatch repair (MMR) in Escherichia coli. The system relies on detection of Lac+ revertants using MMR-proficient or MMR-deficient E. coli strains carrying a lac +1 frameshift mutation expressing hMLH1 proteins. We report that expression of wild-type hMLH1 protein causes an approx. 19-fold increase in mutation rates. The mutator phenotype was due to the ability of hMLH1 protein to interact with bacterial MutL and MutS proteins, thereby interfering with the formation of complexes between MMR proteins and mismatched DNA. Conversely, expression of proteins encoded by alleles deriving from hereditary-non-polyposis-colon-cancer (HNPCC) families decreases mutation rates, depending on the specific amino acid substitutions. These effects parallel the MutL-and MutS-binding and ATP-binding/hydrolysis activities of the mutated proteins.

Replacing the general energy-coupling proteins of the phospho-enol-pyruvate:sugar phosphotransferase system ofSalmonella typhimuriumwith fructose-inducible counterparts results in the inability to utilize nonphosphotransferase system sugars

2007 ◽  
Vol 53 (5) ◽  
pp. 586-598 ◽  
Author(s):  
Sarah L. Sutrina ◽  
Patricia I. Inniss ◽  
Leslie-Ann Lazarus ◽  
Lizette Inglis ◽  
Jacqueline Maximilien
Keyword(s):  
Cyclic Amp ◽  
Rapid Growth ◽  
Regulatory Protein ◽  
Energy Coupling ◽  
Threshold Level ◽  
Luria Bertani ◽  
Wild Type ◽  
Phosphotransferase System ◽  
Inducer Exclusion ◽  
Luria Bertani Broth

A Salmonella typhimurium mutant lacking Enzyme I and HPr, general proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PTS), but producing homologues EIFructoseand FPr constitutively, did not grow in minimal medium supplemented with non-PTS sugars (melibiose, glycerol, and maltose) in the absence of any trace of Luria–Bertani broth; adding cyclic AMP allowed growth. On melibiose, rapid growth began only when melibiose permease activity had reached a threshold level. Wild-type cultures reached this level within about 2 h, but the mutant only after a 12–14 h lag period, and then only when cyclic AMP had been added to the medium. On a mixture of melibiose and a PTS sugar, permease was undetectable in either the wild type or mutant until the PTS sugar had been exhausted. Permease then appeared, increasing with time, but in the mutant it never reached the threshold allowing rapid growth on melibiose unless cyclic AMP had been added. On rich medium supplemented with melibiose or glycerol, the mutant produced lower (30%) levels of melibiose permease or glycerol kinase compared with the wild type. We propose that poor phosphorylation of the regulatory protein Enzyme IIAGlucose, leading to constitutive inducer exclusion and catabolite repression in this strain, accounts for these results.

scholarly journals Altering the Substrate Specificity of Organophosphorus Hydrolase for Enhanced Hydrolysis of Chlorpyrifos

2004 ◽  
Vol 70 (8) ◽  
pp. 4681-4685 ◽  
Author(s):  
Catherine Mee-Hie Cho ◽  
Ashok Mulchandani ◽  
Wilfred Chen
Keyword(s):  
Directed Evolution ◽  
Wide Spectrum ◽  
Crop Protection ◽  
Fold Increase ◽  
Luria Bertani ◽  
Organophosphorus Hydrolase ◽  
Diffusion Control ◽  
Wild Type ◽  
Hydrolysis Rates ◽  
Hydrolysis Of

ABSTRACT Chlorpyrifos is one of the most popular pesticides used for agriculture crop protection, and widespread contamination is a potential concern. However, chlorpyrifos is hydrolyzed almost 1,000-fold slower than the preferred substrate, paraoxon, by organophosphorus hydrolase (OPH), an enzyme that can degrade a broad range of organophosphate pesticides. We have recently demonstrated that directed evolution can be used to generate OPH variants with up to 25-fold improvement in hydrolysis of methyl parathion. The obvious question and challenge are whether similar success could be achieved with this poorly hydrolyzed substrate, chlorpyrifos. For this study, five improved variants were selected from two rounds of directed evolution based on the formation of clear haloes on Luria-Bertani plates overlaid with chlorpyrifos. One variant, B3561, exhibited a 725-fold increase in the k cat/Km value for chlorpyrifos hydrolysis as well as enhanced hydrolysis rates for several other OP compounds tested. Considering that wild-type OPH hydrolyzes paraoxon at a rate close to the diffusion control limit, the 39-fold improvement in hydrolysis of paraoxon by B3561 suggests that this variant is one of the most efficient enzymes available to attack a wide spectrum of organophosphate nerve agents.

The role of OXA-1 β-lactamase Asp66 in the stabilization of the active-site carbamate group and in substrate turnover

2008 ◽  
Vol 410 (3) ◽  
pp. 455-462 ◽  
Author(s):  
David A. Leonard ◽  
Andrea M. Hujer ◽  
Brian A. Smith ◽  
Kyle D. Schneider ◽  
Christopher R. Bethel ◽  
...  
Keyword(s):  
Active Site ◽  
Catalytic Mechanism ◽  
Fold Increase ◽  
Luria Bertani ◽  
Saturation Mutagenesis ◽  
Substrate Affinity ◽  
Luria Bertani Broth ◽  
Class D ◽  
Carbamate Group

The OXA-1 β-lactamase is one of the few class D enzymes that has an aspartate residue at position 66, a position that is proximal to the active-site residue Ser67. In class A β-lactamases, such as TEM-1 and SHV-1, residues adjacent to the active-site serine residue play a crucial role in inhibitor resistance and substrate selectivity. To probe the role of Asp66 in substrate affinity and catalysis, we performed site-saturation mutagenesis at this position. Ampicillin MIC (minimum inhibitory concentration) values for the full set of Asp66 mutants expressed in Escherichia coli DH10B ranged from ≤8 μg/ml for cysteine, proline and the basic amino acids to ≥256 μg/ml for asparagine, leucine and the wild-type aspartate. Replacement of aspartic acid by asparagine at position 66 also led to a moderate enhancement of extended-spectrum cephalosporin resistance. OXA-1 shares with other class D enzymes a carboxylated residue, Lys70, that acts as a general base in the catalytic mechanism. The addition of 25 mM bicarbonate to Luria–Bertani-broth agar resulted in a ≥16-fold increase in MICs for most OXA-1 variants with amino acid replacements at position 66 when expressed in E. coli. Because Asp66 forms hydrogen bonds with several other residues in the OXA-1 active site, we propose that this residue plays a role in stabilizing the CO2 bound to Lys70 and thereby profoundly affects substrate turnover.

scholarly journals Antagonistic Roles for GcvA and GcvB in hdeAB Expression in Escherichia coli

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Lorraine T. Stauffer ◽  
George V. Stauffer
Keyword(s):  
Luria Bertani ◽  
Low Ph ◽  
Wild Type ◽  
E Coli ◽  
Expression In Escherichia Coli ◽  
Luria Bertani Broth ◽  
Periplasmic Proteins ◽  
Acidic Conditions ◽  
Survival And Growth ◽  
Minimal Media

In E. coli, the periplasmic proteins HdeA and HdeB have chaperone-like functions, suppressing aggregation of periplasmic proteins under acidic conditions. A microarray analysis of RNA isolated from an E. coli wild type and a ΔgcvB strain grown to mid-log phase in Luria-Bertani broth indicated the hdeAB operon, encoding the HdeA and HdeB proteins, is regulated by the sRNA GcvB. We wanted to verify that GcvB and its coregulator Hfq play a role in regulation of the hdeAB operon. In this study, we show that GcvB positively regulates hdeA::lacZ and hdeB::lacZ translational fusions in cells grown in Luria-Bertani broth and in glucose minimal media + glycine. Activation also requires the Hfq protein. Although many sRNAs dependent on Hfq regulate by an antisense mechanism, GcvB regulates hdeAB either directly or indirectly at the level of transcription. GcvA, the activator of gcvB, negatively regulates hdeAB at the level of transcription. Although expression of gcvB is dependent on GcvA, activation of hdeAB by GcvB occurs independently of GcvA’s ability to repress the operon. Cell survival and growth at low pH are consistent with GcvA negatively regulating and GcvB positively regulating the hdeAB operon.

Developmental Plasticity and Evolution

2003 ◽  
Author(s):  
Mary Jane West-Eberhard
Keyword(s):  
Adaptive Evolution ◽  
Evolutionary Biology ◽  
Developmental Plasticity ◽  
Higher Plants ◽  
Critical Discussion ◽  
Physiological Adaptation ◽  
Modular Organization ◽  
Random Mutation ◽  
Environmental Induction ◽  
Development And Evolution

The first comprehensive synthesis on development and evolution: it applies to all aspects of development, at all levels of organization and in all organisms, taking advantage of modern findings on behavior, genetics, endocrinology, molecular biology, evolutionary theory and phylogenetics to show the connections between developmental mechanisms and evolutionary change. This book solves key problems that have impeded a definitive synthesis in the past. It uses new concepts and specific examples to show how to relate environmentally sensitive development to the genetic theory of adaptive evolution and to explain major patterns of change. In this book development includes not only embryology and the ontogeny of morphology, sometimes portrayed inadequately as governed by "regulatory genes," but also behavioral development and physiological adaptation, where plasticity is mediated by genetically complex mechanisms like hormones and learning. The book shows how the universal qualities of phenotypes--modular organization and plasticity--facilitate both integration and change. Here you will learn why it is wrong to describe organisms as genetically programmed; why environmental induction is likely to be more important in evolution than random mutation; and why it is crucial to consider both selection and developmental mechanism in explanations of adaptive evolution. This book satisfies the need for a truly general book on development, plasticity and evolution that applies to living organisms in all of their life stages and environments. Using an immense compendium of examples on many kinds of organisms, from viruses and bacteria to higher plants and animals, it shows how the phenotype is reorganized during evolution to produce novelties, and how alternative phenotypes occupy a pivotal role as a phase of evolution that fosters diversification and speeds change. The arguments of this book call for a new view of the major themes of evolutionary biology, as shown in chapters on gradualism, homology, environmental induction, speciation, radiation, macroevolution, punctuation, and the maintenance of sex. No other treatment of development and evolution since Darwin's offers such a comprehensive and critical discussion of the relevant issues. Developmental Plasticity and Evolution is designed for biologists interested in the development and evolution of behavior, life-history patterns, ecology, physiology, morphology and speciation. It will also appeal to evolutionary paleontologists, anthropologists, psychologists, and teachers of general biology.

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