scholarly journals Historical Contingency Causes Divergence in Adaptive Expression of the lac Operon

2021 ◽  
Author(s):  
Kedar Karkare ◽  
Huei-Yi Lai ◽  
Ricardo B R Azevedo ◽  
Tim F Cooper
Keyword(s):  
Promoter Region ◽  
Potential Benefit ◽  
Constitutive Expression ◽  
High Rate ◽  
Mutation Rates ◽  
Lac Operon ◽  
Historical Contingency ◽  
Fitness Effect ◽  
Fluctuating Environments ◽  
Laci Repressor

Abstract Populations of Escherichia coli selected in constant and fluctuating environments containing lactose often adapt by substituting mutations in the lacI repressor that cause constitutive expression of the lac operon. These mutations occur at a high rate and provide a significant benefit. Despite this, eight of 24 populations evolved for 8,000 generations in environments containing lactose contained no detectable repressor mutations. We report here on the basis of this observation. We find that, given relevant mutation rates, repressor mutations are expected to have fixed in all evolved populations if they had maintained the same fitness effect they confer when introduced to the ancestor. In fact, reconstruction experiments demonstrate that repressor mutations have become neutral or deleterious in those populations in which they were not detectable. Populations not fixing repressor mutations nevertheless reached the same fitness as those that did fix them, indicating that they followed an alternative evolutionary path that made redundant the potential benefit of the repressor mutation, but involved unique mutations of equivalent benefit. We identify a mutation occurring in the promoter region of the uspB gene as a candidate for influencing the selective choice between these paths. Our results detail an example of historical contingency leading to divergent evolutionary outcomes.

scholarly journals The Distribution Frequency of Interferon-Gamma Receptor 1 Gene Polymorphisms in Interferon-γ Release Assay-Positive Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-5
Author(s):  
Changguo Chen ◽  
Lei Chen ◽  
Changwei Chen ◽  
Qiuyuan Chen ◽  
Qiangyuan Zhao ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Promoter Region ◽  
Gene Polymorphisms ◽  
Statistical Significance ◽  
Interferon Γ ◽  
Mutation Rates ◽  
Gamma Receptor ◽  
Release Assay ◽  
Positive Groups ◽  
Distribution Frequency

Tuberculosis is caused by mycobacterium, a potentially fatal infectious bacterium. In recent years, TB cases increased in the whole world. WHO statistics data shows that the world’s annual tuberculosis incidence was 8~10 million with about 3 million deaths. Several studies have shown that susceptibility to tuberculosis may be associated with IFNGR1 gene polymorphisms. Here, we report the distribution frequency of IFNGR1 gene polymorphisms in 103 cases of IGA-negative patients and 100 cases of IGA-positive patients from China by sequencing the IFNGR1 proximal ~750 bp promoter region. We found a total of 5 types of site mutations: -611 (G/A), -56 (T/C), -255 (C/T), -359 (T/C), and -72 (C/T). The two main types of gene polymorphisms among the IGA-negative and IGA-positive groups were -611 (G/A), with mutation rates of 88.3% and 78.4%, respectively, and -56 (T/C), with mutation rates of 84.5% and 83.8%, respectively, which had no statistical significance, and there was no correlation with the incidence of tuberculosis.

scholarly journals Tandem Repeat of a Transcriptional Enhancer Upstream of the Sterol 14α-Demethylase Gene (CYP51) inPenicillium digitatum

2000 ◽  
Vol 66 (8) ◽  
pp. 3421-3426 ◽  
Author(s):  
Hiroshi Hamamoto ◽  
Koji Hasegawa ◽  
Ryoji Nakaune ◽  
Young Jin Lee ◽  
Yoshiyuki Makizumi ◽  
...  
Keyword(s):  
Filamentous Fungi ◽  
Tandem Repeat ◽  
Resistant Strain ◽  
Fungicide Resistance ◽  
Promoter Region ◽  
Resistance Mechanism ◽  
Constitutive Expression ◽  
Structural Genes ◽  
Transcriptional Enhancer ◽  
Resistant Strains

ABSTRACT We investigated the mechanism of resistance to demethylation inhibitors (DMI) in Penicillium digitatum by isolating theCYP51 gene, which encodes the target enzyme (P45014DM) of DMI, from three DMI-resistant and three DMI-sensitive strains. The structural genes of all six strains were identical, but in the promoter region, a unique 126-bp sequence was tandemly repeated five times in the DMI-resistant strains and was present only once in the DMI-sensitive strains. Constitutive expression of CYP51 in the resistant strains was about 100-fold higher than that in the sensitive strains. We introduced CYP51, including the promoter region, from a DMI-resistant strain into a DMI-sensitive strain, which rendered the transformants DMI resistant and increased CYP51 expression. We also found that if the number of copies of the repeat was reduced to two, resistance andCYP51 expression also decreased. These results indicate that the 126-bp unit acts as a transcriptional enhancer and that a tandem repeat of the unit enhances CYP51 expression, resulting in DMI resistance. This is a new fungicide resistance mechanism for filamentous fungi.

scholarly journals Spontaneous point mutations that occur more often when advantageous than when neutral.

Genetics ◽  
1990 ◽  
Vol 126 (1) ◽  
pp. 5-16 ◽  
Author(s):  
B G Hall
Keyword(s):  
Physiological Stress ◽  
Point Mutations ◽  
Constitutive Expression ◽  
Lac Operon ◽  
Heuristic Model ◽  
Reversion Rate ◽  
Valine Resistance ◽  
Widespread Belief ◽  
Dying Cells ◽  
Delayed Growth

Abstract Recent reports have called into question the widespread belief "that mutations arise continuously and without any consideration for their utility" (in the words of J. Cairns) and have suggested that some mutations (which Cairns called "directed" mutations) may occur as specific responses to environmental challenges, i.e., they may occur more often when advantageous than when neutral. In this paper it is shown that point mutations in the trp operon reverted to trp+ more frequently under conditions of prolonged tryptophan deprivation when the reversions were advantageous, than in the presence of tryptophan when the reversions were neutral. The overall mutation rate, as determined from the rates of mutation to valine resistance and to constitutive expression of the lac operon, did not increase during tryptophan starvation. The trp reversion rate did not increase when the cells were starved for cysteine for a similar period, indicating that the increased reversion rate was specific to conditions where the reversions were advantageous. Two artifactual explanations for the observations, delayed growth of some preexisting revertants and cryptic growth by some cells at the expense of dying cells within aged colonies, were tested and rejected as unlikely. The trp+ reversions that occurred while trp- colonies aged in the absence of tryptophan were shown to be time-dependent rather than replication-dependent, and it is suggested that they occur by mechanisms different from those that have been studied in growing cells. A heuristic model for the molecular basis of such mutations is proposed and evidence consistent with that model is discussed. It is suggested that the results in this and previous studies can be explained on the basis of underlying random mechanisms that act during prolonged periods of physiological stress, and that "directed" mutations are not necessarily the basis of those observations.

The harvest-responsive region of the Asparagus officinalis sparagine synthetase promoter reveals complexity in the regulation of the harvest response

2008 ◽  
Vol 35 (12) ◽  
pp. 1212 ◽  
Author(s):  
Donald A. Hunter ◽  
Lyn M. Watson
Keyword(s):  
Promoter Region ◽  
Constitutive Expression ◽  
Wound Response ◽  
Asparagus Officinalis ◽  
Minimal Promoter ◽  
Nucleotide Substitutions ◽  
Cis Acting ◽  
Gus Reporter ◽  
Highly Active ◽  
Responsive Element

The activity of a 1915-bp asparagine synthetase (AS) promoter of Asparagus officinalis L. was induced in mature leaves of transgenic Arabidopsis thaliana (L.) Heynh. plants when the leaves were detached and held in water for 24 h. To understand this induction by harvest, variants of the AS promoter were linked to the β-glucuronidase GUS reporter gene. Harvest induction in the leaves required detachment and was not simply a wound response. Two regions in the AS promoter (Region A, –640 to –523; Region B, –524 to –383) were independently able to confer harvest response to the otherwise unresponsive –383AS (minimal) promoter. Region A was studied in further detail. Various truncations, deletions, or nucleotide substitutions of Region A affected activity and fold induction of the minimal promoter. However, no harvest-inducible cis-acting element within Region A was identified. Although the minimal promoter contained a dehydration-responsive element and ACGT elements similar to ABA-responsive regulatory motifs these were not needed by the upstream regulatory regions for directing harvest response. When four copies of Region A were linked to the minimal promoter it became highly active in leaves before harvest. Deletions within Region A showed that it required its complete 117 bp for driving harvest response, yet the region cannot simply be thought of as a harvest-responsive module, since its concatemerisation led to constitutive expression.

scholarly journals Isolation and Characterization of thenikR Gene Encoding a Nickel-Responsive Regulator inEscherichia coli

1999 ◽  
Vol 181 (2) ◽  
pp. 670-674 ◽  
Author(s):  
Karinne De Pina ◽  
Valerie Desjardin ◽  
Marie-Andree Mandrand-Berthelot ◽  
Gerard Giordano ◽  
Long-Fei Wu
Keyword(s):  
Promoter Region ◽  
Constitutive Expression ◽  
Inescherichia Coli ◽  
Start Site ◽  
High Concentration ◽  
Transcription Start ◽  
Gene Encoding ◽  
Isolation And Characterization ◽  
Specific Transport System

ABSTRACT Expression of the nickel-specific transport system encoded by theEscherichia coli nikABCDE operon is repressed by a high concentration of nickel. By using random transposon Tn10 insertion, we isolated mutants in which expression of the nik operon became constitutive with respect to nickel. We have identified the corresponding nikR gene which encodes a nickel-responsive regulator. Expression of nikRwas partially controlled by Fnr through transcription from thenikA promoter region. In addition, a specific transcription start site for the constitutive expression of nikR was found 51 bp upstream of the nikR gene.

scholarly journals Divergent evolution of mutation rates and biases in the long-term evolution experiment with Escherichia coli

2020 ◽  
Author(s):  
Rohan Maddamsetti ◽  
Nkrumah A. Grant
Keyword(s):  
Escherichia Coli ◽  
Point Mutations ◽  
Long Term Evolution ◽  
Dna Topology ◽  
Mutation Rates ◽  
Rate Variation ◽  
Historical Contingency ◽  
Term Evolution ◽  
Evolution Experiment

ABSTRACTAll organisms encode enzymes that replicate, maintain, pack, recombine, and repair their genetic material. For this reason, mutation rates and biases also evolve by mutation, variation, and natural selection. By examining metagenomic time series of the Lenski long-term evolution experiment (LTEE) with Escherichia coli (Good, et al. 2017), we find that local mutation rate variation has evolved during the LTEE. Each LTEE population has evolved idiosyncratic differences in their rates of point mutations, indels, and mobile element insertions, due to the fixation of various hypermutator and antimutator alleles. One LTEE population, called Ara+3, shows a strong, symmetric wave pattern in its density of point mutations, radiating from the origin of replication. This pattern is largely missing from the other LTEE populations, most of which evolved missense, indel, or structural mutations in topA, fis, and dusB— loci that all affect DNA topology. The distribution of mutations in those genes over time suggests epistasis and historical contingency in the evolution of DNA topology, which may have in turn affected local mutation rates. Overall, the replicate populations of the LTEE have largely diverged in their mutation rates and biases, even though they have adapted to identical abiotic conditions.

scholarly journals Sp1 and Sp3 control constitutive expression of the human NHE2 promoter by interactions with the proximal promoter and the transcription initiation site

2007 ◽  
Vol 407 (1) ◽  
pp. 101-111 ◽  
Author(s):  
Ian Pearse ◽  
Ying X. Zhu ◽  
Eleanor J. Murray ◽  
Pradeep K. Dudeja ◽  
Krishnamurthy Ramaswamy ◽  
...  
Keyword(s):  
Transcription Initiation ◽  
Promoter Region ◽  
Promoter Activity ◽  
Critical Role ◽  
Constitutive Expression ◽  
Regulatory Elements ◽  
Initiation Site ◽  
Transcription Initiation Site ◽  
Proximal Promoter ◽  
Gc Box

We have previously cloned the human Na+/H+ exchanger NHE2 gene and its promoter region. In the present study, the regulatory elements responsible for the constitutive expression of NHE2 were studied. Transient transfection assays revealed that the −40/+150 promoter region contains the core promoter responsible for the optimal promoter activity. A smaller fragment, −10/+40, containing the TIS (transcription initiation site) showed minimal activity. We identified a palindrome that overlaps the TIS and binds to the transcription factors Sp1 and Sp3. Mutations in the 5′ flank of the palindrome abolished the Sp1/Sp3 interaction and reduced promoter activity by approx. 45%. In addition, a conserved GC-box centered at −25 was found to play a critical role in basal promoter activity and also interacted with Sp1 and Sp3. An internal deletion in the GC-box severely reduced the promoter activity. Sp1/Sp3 binding to these elements was established using gel-mobility shift assays, confirmed by chromatin immunoprecipitation and co-transfections in Drosophila SL2 cells. Furthermore, we identified two positive regulatory elements in the DNA region corresponding to the 5′-UTR (5′-untranslated region). The results in the present study indicate that Sp1 and Sp3 are required for constitutive NHE2 expression and that the positive regulatory elements of the 5′-UTR may co-operate with the 5′-flanking region to achieve the optimal promoter activity.

scholarly journals Intron-independent Association of Splicing Factors with Active Genes

1999 ◽  
Vol 145 (6) ◽  
pp. 1133-1143 ◽  
Author(s):  
Caroline Jolly ◽  
Claire Vourc'h ◽  
Michel Robert-Nicoud ◽  
Richard I. Morimoto
Keyword(s):  
Heat Shock ◽  
Human Fibroblasts ◽  
Constitutive Expression ◽  
High Rate ◽  
Heat Shock Gene ◽  
Specific Gene ◽  
Splicing Factors ◽  
Hsp70 Gene ◽  
Transcription Sites ◽  
Discrete Domains

The cell nucleus is organized as discrete domains, often associated with specific events involved in chromosome organization, replication, and gene expression. We have examined the spatial and functional relationship between the sites of heat shock gene transcription and the speckles enriched in splicing factors in primary human fibroblasts by combining immunofluorescence and fluorescence in situ hybridization (FISH). The hsp90α and hsp70 genes are inducibly regulated by exposure to stress from a low basal level to a high rate of transcription; additionally the hsp90α gene contains 10 introns whereas the hsp70 gene is intronless. At 37°C, only 30% of hsp90α transcription sites are associated with speckles whereas little association is detected with the hsp70 gene, whose constitutive expression is undetectable relative to the hsp90α gene. Upon exposure of cells to heat shock, the heavy metal cadmium, or the amino acid analogue azetidine, transcription at the hsp90α and hsp70 gene loci is strongly induced, and both hsp transcription sites become associated with speckles in >90% of the cells. These results reveal a clear disconnection between the presence of intervening sequences at specific gene loci and the association with splicing factor–rich regions and suggest that subnuclear structures containing splicing factors are associated with sites of transcription.

scholarly journals Phylogenetic Evidence for the Rapid Evolution of Human B19 Erythrovirus

2006 ◽  
Vol 80 (7) ◽  
pp. 3666-3669 ◽  
Author(s):  
Laura A. Shackelton ◽  
Edward C. Holmes
Keyword(s):  
Host Cell ◽  
Evolutionary Dynamics ◽  
Rna Viruses ◽  
Rapid Evolution ◽  
Evolutionary Change ◽  
High Rate ◽  
Mutation Rates ◽  
Genome Replication ◽  
Nucleotide Substitutions ◽  
Viral Pathogen

ABSTRACT Human B19 erythrovirus is a ubiquitous viral pathogen, commonly infecting individuals before adulthood. As with all autonomous parvoviruses, its small single-stranded DNA genome is replicated with host cell machinery. While the mechanism of parvovirus genome replication has been studied in detail, the rate at which B19 virus evolves is unknown. By inferring the phylogenetic history and evolutionary dynamics of temporally sampled B19 sequences, we observed a surprisingly high rate of evolutionary change, at approximately 10−4 nucleotide substitutions per site per year. This rate is more typical of RNA viruses and suggests that high mutation rates are characteristic of the Parvoviridae.

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