scholarly journals Statistical concepts in the theory of bacterial mutation

1953 ◽  
Vol 51 (2) ◽  
pp. 162-184 ◽  
Author(s):  
P. Armitage
Keyword(s):  
Mutation Rate ◽  
Phenotypic Expression ◽  
Theoretical Distribution ◽  
Mutation Rates ◽  
Safe Procedure ◽  
Short Term ◽  
Mutant Type ◽  
Bacterial Populations ◽  
Long Term Experiment

This paper is a short exposition of the mathematical and statistical theory of the growth of bacterial populations subject to mutation.A mathematical model for the long-term development of a mixed population with two types of organism is proposed. The proportion of organisms which are of the mutant type eventually approaches an asymptotic value, which is independent of the initial composition of the population. A procedure is outlined for estimating the forward and backward mutation rates from a long-term experiment.The exact interpretation of the constants representing mutation rates requires some assumption about the point of time, during an individual life cycle, at which mutations occur. The usual assumption is that mutations can occur with equal frequency at all instants during the cycle.In short-term experiments, in which the proportion of mutants is at all times negligible, it is important to consider the variation between the numbers of mutants developing in replicate cultures. The theoretical distribution of Lea & Coulson may be disturbed by the failure of any one of a number of assumptions; the effects of such disturbances are considered in some detail.Various methods of estimating the mutation rate from an observed series of replicate cultures are examined. Two of the main sources of disturbance of the theoretical distribution may be delay of phenotypic expression, and the existence of multinucleate cells with dominant mutation. These factors affect particularly the lower tail of the distribution, and it is suggested that a fairly safe procedure may be to estimate the mutation rate from the upper quartile of the observed distribution. Tables 3 and 4 enable the estimate of the mutation rate, together with 95% confidence limits, to be readily calculated.

scholarly journals Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria

2017 ◽  
Author(s):  
Antoine Frénoy ◽  
Sebastian Bonhoeffer
Keyword(s):  
Population Dynamics ◽  
Mutation Rate ◽  
Death Rate ◽  
Mutation Rates ◽  
Resistance Mutations ◽  
Bacterial Populations ◽  
Plasmid Segregation ◽  
Genome Wide ◽  
Response To Stress ◽  
Induced Mutagenesis

AbstractThe stress-induced mutagenesis paradigm postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to withstand the stress. This has implications for antibiotic treatment: exposure to sub-inhibitory doses of antibiotics has been reported to increase bacterial mutation rates, and thus probably the rate at which resistance mutations appear and lead to treatment failure.Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet sub-inhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus giving more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress.We developed a system using plasmid segregation to measure death and growth rates simultaneously in bacterial populations. We use it to replicate classical experiments reporting antibiotic-induced mutagenesis. We found that a substantial death rate occurs at the tested sub-inhibitory concentrations, and taking this death into account lowers and sometimes removes the signal for stress-induced mutagenesis. Moreover even when antibiotics increase mutation rate, sub-inhibitory treatments do not increase genetic diversity and evolvability, again because of effects of the antibiotics on population dynamics.Beside showing that population dynamic is a crucial but neglected parameter affecting evolvability, we provide better experimental and computational tools to study evolvability under stress, leading to a re-assessment of the magnitude and significance of the stress-induced mutagenesis paradigm.

The Safety of Ultrasound Guided Tenotomy for Upper and Lower Extremity Tendinopathies: A Retrospective Study

2020 ◽  
Author(s):  
Benjamin Fick ◽  
Daniel Stover ◽  
Ruth Chimenti ◽  
Mederic Hall
Keyword(s):  
Lower Extremity ◽  
Physical Function ◽  
Complication Rate ◽  
Plantar Fascia ◽  
Safe Procedure ◽  
Ultrasound Guided ◽  
Short Term ◽  
Long Term Follow Up

Abstract Background: Ultrasound guided tenotomy (USGT) is a minimally invasive treatment option for patients with chronic tendinopathy who fail to benefit from conservative exercise interventions. The complication rate and effectiveness of USGT remain poorly defined in the literature. Purpose: This study aimed to evaluate the risks associated with USGT and outcomes across upper extremity and lower extremity tendinopathy/fasciopathy sites. Methods Patients who had USGT at the elbow, patellar, or Achilles tendons or along the plantar fascia were identified by retrospective review of charts. Screening for complications (infection, tendon rupture, and hypersensitivity) and satisfaction with the procedure were assessed at routine short-term follow-up visits and at long-term follow-up via phone/email. Outcomes (pain, quality of life) were assessed using the region specific pain scales and the Short Form-12, respectively, at baseline prior to the procedure, short-term follow up, and long term follow up. Results: A total of 262 patients were identified through chart review. There was a low complication rate of 0.7% including one superficial wound infection and one case of wound hypersensitivity. Prior to USGT, the majority of patients reported moderate/daily pain that decreased by short-term and long-term follow-up to mild/occasional pain (p < 0.05). Additionally, most patients reported abnormally low physical function prior to USGT that was within normal range of physical function by long-term follow-up (p < 0.05). The majority of responders (63% at the plantar fascia to 92% at the Achilles midportion) reported being either ‘very satisfied’ or ‘somewhat satisfied’ with the procedure at short-term follow-up. Conclusions: This study found that USGT is a safe procedure with a low complication rate in a heterogeneous sample. Study findings provide preliminary evidence on the utility of USGT to reduce pain and improve function with a high rate of patient satisfaction.

scholarly journals A systematic review of the literature assessing the outcomes of stapled haemorrhoidopexy versus open haemorrhoidectomy

2020 ◽  
Author(s):  
Q. Z. Ruan ◽  
W. English ◽  
A. Hotouras ◽  
C. Bryant ◽  
F. Taylor ◽  
...  
Keyword(s):  
Systematic Review ◽  
Patient Satisfaction ◽  
Safe Procedure ◽  
Stapled Haemorrhoidopexy ◽  
Short Term ◽  
Period 2 ◽  
Number Of Patients ◽  
Study Characteristics ◽  
The Moment

Abstract Background Symptomatic haemorrhoids affect a large number of patients throughout the world. The aim of this systematic review was to compare the surgical outcomes of stapled haemorrhoidopexy (SH) versus open haemorrhoidectomy (OH) over a 20-year period. Methods Randomized controlled trials published between January 1998 and January 2019 were extracted from Pubmed using defined search criteria. Study characteristics and outcomes in the form of short-term and long-term complications of the two techniques were analyzed. Any changes in trend of outcomes over time were assessed by comparing article groups 1998–2008 and 2009–2019. Results Twenty-nine and 9 relevant articles were extracted for the 1998–2008 (period 1) and 2009–2019 (period 2) cohorts, respectively. Over the two time periods, SH was found to be a safe procedure, associated with statistically reduced operative time (in 13/21 studies during period 1 and in 3/8 studies during period 2), statistically less intraoperative bleeding (3/7 studies in period 1 and 1/1 study in period 2) and consistently less early postoperative pain on the visual analogue scale (12/15 studies in period 1 and 4/5 studies in period 2) resulting in shorter hospital stay (12/20 studies in period 1 and 2/2 studies in period 2) at the expense of a higher cost. In the longer term, although chronic pain in SH and OH patents is comparable, patient satisfaction with SH may decline with time and at 2-year follow-up OH appeared to be associated with greater patient satisfaction. Conclusions SH appears to be safe with potential advantages, at least in the short term, but the evidence is lacking at the moment to suggest its routine use in clinical practice.

scholarly journals The evolution of bacterial mutation rates under simultaneous selection by interspecific and social parasitism

2013 ◽  
Vol 280 (1773) ◽  
pp. 20131913 ◽  
Author(s):  
Siobhán O'Brien ◽  
Antonio M. M. Rodrigues ◽  
Angus Buckling
Keyword(s):  
Mutation Rate ◽  
Social Parasitism ◽  
Mutation Rates ◽  
Bacterial Populations ◽  
Simultaneous Selection ◽  
Bacterial Mutation ◽  
Selection For ◽  
Intraspecific Parasitism ◽  
Theory And Experiments ◽  
Mutation Rate Evolution

Many bacterial populations harbour substantial numbers of hypermutable bacteria, in spite of hypermutation being associated with deleterious mutations. One reason for the persistence of hypermutators is the provision of novel mutations, enabling rapid adaptation to continually changing environments, for example coevolving virulent parasites. However, hypermutation also increases the rate at which intraspecific parasites (social cheats) are generated. Interspecific and intraspecific parasitism are therefore likely to impose conflicting selection pressure on mutation rate. Here, we combine theory and experiments to investigate how simultaneous selection from inter- and intraspecific parasitism affects the evolution of bacterial mutation rates in the plant-colonizing bacterium Pseudomonas fluorescens. Both our theoretical and experimental results suggest that phage presence increases and selection for public goods cooperation (the production of iron-scavenging siderophores) decreases selection for mutator bacteria. Moreover, phages imposed a much greater growth cost than social cheating, and when both selection pressures were imposed simultaneously, selection for cooperation did not affect mutation rate evolution. Given the ubiquity of infectious phages in the natural environment and clinical infections, our results suggest that phages are likely to be more important than social interactions in determining mutation rate evolution.

scholarly journals Long-term resource addition to a detrital food web yields a pattern of responses more complex than pervasive bottom-up control

2017 ◽  
Author(s):  
Kendra L. Lawrence ◽  
David H Wise
Keyword(s):  
Field Experiments ◽  
Abiotic Factors ◽  
Short Term ◽  
Bottom Up ◽  
Term Experiment ◽  
Two Factors ◽  
Long Term Experiment ◽  
Short Term Experiment ◽  
Univariate Analyses

Background. Theory predicts strong bottom-up control in detritus-based food webs, yet field experiments with detritus-based terrestrial systems have uncovered contradictory evidence regarding the strength and pervasiveness of bottom-up control processes. Two factors likely leading to contradictory results are experiment duration, which influences exposure to temporal variation in abiotic factors such as rainfall and affects the likelihood of detecting approach to a new equilibrium; and openness of the experimental units to immigration and migration. To investigate the contribution of these two factors, we conducted a long-term experiment with open and fenced plots in the forest that was the site of an earlier, short-term experiment (3.5 months) with open plots (Chen & Wise 1999) that produced evidence of strong bottom-up control for 14 taxonomic groupings of primary consumers of litter and fungi (microbi-detritivores) and their predators. Methods. We added artificial high-quality detritus to ten 2 x 2-m forest-floor plots at bi-weekly intervals from April through September in three consecutive years (Supplemented treatment). Ten comparable Ambient plots were controls. Half of the Supplemented and Ambient plots were enclosed by metal fencing. Results. Arthropod community structure (based upon 18 response variables) diverged over time between Supplemented and Ambient treatments, with no effect of Fencing on the multivariate response pattern. Fencing possibly influenced only ca. 20% of the subsequent univariate analyses. Multi- and univariate analyses revealed bottom-up control by fall of Year 1 of some, but not all, microbi-detritivores and predators. During the following two years the pattern of responses became more complex than that observed by Chen & Wise (1999). Some taxa showed consistent bottom-up control whereas many did not. Variation across years could not be explained completely by differences in rainfall because some taxa exhibited negative, not positive, responses to detrital supplementation. Discussion. Our 3-yr experiment did not confirm the conclusion of strong, pervasive bottom-up control of microbi-detritivores and predators reported by Chen and Wise (1999). Our longer-term experiment revealed a more complex pattern of responses, a pattern much closer to the range of outcomes reported in the literature for many short-term experiments. Much of the variation in responses across studies likely reflects variation in factors such as rainfall and the quality of added detritus. Nevertheless, it is also possible that long-term resource enhancement can drive a community towards a new equilibrium state that differs from what would have been predicted from the initial short-term responses exhibited by primary and secondary consumers.

scholarly journals Sulfur-Based Denitrification in Streambank Subsoils in a Headwater Catchment Underlain by Marine Sedimentary Rocks in Akita, Japan

2021 ◽  
Vol 9 ◽  
Author(s):  
Atsushi Hayakawa ◽  
Hitoshi Ota ◽  
Ryoki Asano ◽  
Hirotatsu Murano ◽  
Yuichi Ishikawa ◽  
...  
Keyword(s):  
Bacterial Flora ◽  
Terrestrial Ecosystems ◽  
Stoichiometric Ratio ◽  
Short Term ◽  
Incubation Experiments ◽  
Long Term Experiment ◽  
Sulfide Content ◽  
Sulfur Oxidizing ◽  
Headwater Catchment

Sulfur-based denitrification may be a key biogeochemical nitrate (NO3−) removal process in sulfide-rich regions, but it is still poorly understood in natural terrestrial ecosystems. We examined sulfur-driven NO3− reduction using streambank soils in a headwater catchment underlain by marine sedimentary rock in Akita, Japan. In a catchment exhibiting higher sulfide content in streambed sediment, we sampled two adjacent streambank soils of streambank I (two layers) and of streambank II (eight layers). Anaerobic long-term incubation experiments (40 days, using soils of streambank I) and short-term incubation experiments (5 days, using soils of streambank II) were conducted to evaluate variations of N solutes (NO3−, NO2−, and NH4+), N gases (NO, N2O), and the bacterial flora. In both experiments, two treatment solutions containing NO3− (N treatment), and NO3− and S2O32− (N + S treatment) were prepared. In the N + S treatment of the long-term experiment, NO3− concentrations gradually decreased by 98%, with increases in the SO42−, NO2−, NO, and N2O concentrations and with not increase in the NH4+, indicating denitrification had occurred with a high probability. Temporal accumulation of NO2− was observed in the N + S treatment. The stoichiometric ratio of SO42− production and NO3− depletion rates indicated that denitrification using reduced sulfur occurred even without additional S, indicating inherent S also served as an electron donor for denitrification. In the short-term incubation experiment, S addition was significantly decreased NO3− concentrations and increased NO2−, NO, and N2O concentrations, especially in some subsoils with higher sulfide contents. Many denitrifying sulfur-oxidizing bacteria (Thiobacillus denitrificans and Sulfuricella denitrificans) were detected in both streambank I and II, which dominated up to 5% of the entire microbial population, suggesting that these bacteria are widespread in sulfide-rich soil layers in the catchment. We concluded that the catchment with abundant sulfides in the subsoil possessed the potential for sulfur-driven NO3− reduction, which could widely influence N cycling in and NO3− export from the headwater catchment.

scholarly journals Evolutionary rescue of a green alga kept in the dark

2013 ◽  
Vol 9 (1) ◽  
pp. 20120823 ◽  
Author(s):  
Graham Bell
Keyword(s):  
Short Term ◽  
Term Experiment ◽  
Evolutionary Rescue ◽  
Extreme Phenotypes ◽  
Long Term Experiment ◽  
Sexual Histories ◽  
Dark Conditions ◽  
Set Up ◽  
Asexual Populations

Chlamydomonas (Chlorophyta) can grow as a heterotroph on medium supplemented with acetate in the dark. A long-term experiment to investigate adaptation to dark conditions was set up with hundreds of replicate lines. Growth was initially slow, and most lines became extinct when transferred every few weeks. Some lines survived through the expansion of lineages derived from cells with extreme phenotypes and exhibited a U-shaped curve of collapse and recovery. Two short-term experiments were set up to evaluate the effect of sex on the frequency of ‘evolutionary rescue’ by deriving replicate lines from ancestral populations with contrasting sexual histories that had been cultured in the light for hundreds of generations. When transferred to dark conditions of growth, lines derived from obligately sexual populations survived more often than lines derived from facultatively sexual or asexual populations. This reflected the higher initial frequency of cells able to grow in the dark, due to greater genetic diversity supported by sexual fusion and recombination. The greater probability of evolutionary rescue suggests a general reason for the prevalence of sexual species.

MUTATION RATES FOR ENZYME AND MORPHOLOGICAL LOCI IN BARLEY (HORDEUM VULGARE L.)

Genetics ◽  
1984 ◽  
Vol 106 (4) ◽  
pp. 729-734
Author(s):  
A L Kahler ◽  
R W Allard ◽  
R D Miller
Keyword(s):  
Mutation Rate ◽  
Spontaneous Mutation ◽  
Mutation Rates ◽  
Isogenic Line ◽  
Probability Level ◽  
Short Term ◽  
Hordeum Vulgare L ◽  
Spontaneous Mutation Rate ◽  
Enzyme Loci ◽  
Morphological Variants

ABSTRACT Spontaneous mutation rates were estimated by assaying 84,126 seedlings of a highly homozygous barley line (isogenic line 2025) for five enzyme loci. No mutants were observed in 841,260 allele replications. This result excludes, at probability level 0.95, a spontaneous mutation rate larger than 3.56 x 10-6/locus/gamete/generation for these enzyme loci. Isogenic line 2025 also was scored for mutants at four loci governing morphological variants. No mutants were observed in 3,386,850 allele replications which indicates that the upper bound for the mutation rate for these loci is 8.85 x 10-7. It was concluded that, even though spontaneous mutation has been important in creating variability in the barley species at the loci scored, the rate is too low to have much affect on the short-term dynamics of barley populations.

scholarly journals Mutator genomes decay, despite sustained fitness gains, in a long-term experiment with bacteria

2017 ◽  
Vol 114 (43) ◽  
pp. E9026-E9035 ◽  
Author(s):  
Alejandro Couce ◽  
Larissa Viraphong Caudwell ◽  
Christoph Feinauer ◽  
Thomas Hindré ◽  
Jean-Paul Feugeas ◽  
...  
Keyword(s):  
Evolutionary Biology ◽  
Mutation Accumulation ◽  
Mutation Rates ◽  
Weak Selection ◽  
Bacterial Genomes ◽  
Random Drift ◽  
Strong Linkage ◽  
Term Experiment ◽  
Long Term Experiment

Understanding the extreme variation among bacterial genomes remains an unsolved challenge in evolutionary biology, despite long-standing debate about the relative importance of natural selection, mutation, and random drift. A potentially important confounding factor is the variation in mutation rates between lineages and over evolutionary history, which has been documented in several species. Mutation accumulation experiments have shown that hypermutability can erode genomes over short timescales. These results, however, were obtained under conditions of extremely weak selection, casting doubt on their general relevance. Here, we circumvent this limitation by analyzing genomes from mutator populations that arose during a long-term experiment with Escherichia coli, in which populations have been adaptively evolving for >50,000 generations. We develop an analytical framework to quantify the relative contributions of mutation and selection in shaping genomic characteristics, and we validate it using genomes evolved under regimes of high mutation rates with weak selection (mutation accumulation experiments) and low mutation rates with strong selection (natural isolates). Our results show that, despite sustained adaptive evolution in the long-term experiment, the signature of selection is much weaker than that of mutational biases in mutator genomes. This finding suggests that relatively brief periods of hypermutability can play an outsized role in shaping extant bacterial genomes. Overall, these results highlight the importance of genomic draft, in which strong linkage limits the ability of selection to purge deleterious mutations. These insights are also relevant to other biological systems evolving under strong linkage and high mutation rates, including viruses and cancer cells.

Sign in / Sign up

Export Citation Format

Share Document