scholarly journals Fitness-valley crossing in subdivided asexual populations

2016 ◽  
Author(s):  
Michael R. McLaren
Keyword(s):  
Quantitative Description ◽  
Natural Populations ◽  
Asexual Population ◽  
Migration Rates ◽  
Large Populations ◽  
Subdivided Populations ◽  
The Mean ◽  
And Migration ◽  
Asexual Populations ◽  
Mean Time

AbstractAdaptations may require multiple mutations that are beneficial only in combination. To adapt, a lineage must acquire mutations that are individually neutral or deleterious before gaining the beneficial combination, thereby crossing a plateau or valley, respectively, in the mapping from genotype to fitness. Spatial population structure can facilitate plateau and valley crossing by allowing neutral and deleterious lineages to survive longer and produce more beneficial mutants. Here, we analyze adaptation across a two-mutation plateau or valley in an asexual population that is subdivided into discrete subpopulations, or demes, connected by migration. We describe how subdivision alters the dynamics of adaptation from those in an equally sized unstructured population and give a complete quantitative description of these dynamics for the island migration model. Subdivision can significantly decrease the waiting time for the adaptation if demes and migration rates are small enough that single-mutant lineages fix in one or more demes before producing the beneficial double mutant. But, the potential decrease is small in very large populations and may also be limited by the slow spread of the beneficial mutant in extremely subdivided populations. Subdivision has a smaller effect on the probability that the population adapts very quickly than on the mean time to adapt, which has important consequences in some applications, such as the development of cancer. Our results provide a general and intuitive framework for predicting the effects of spatial structure in other models and in natural populations.

scholarly journals Accumulation of mutations in sexual and asexual populations

1987 ◽  
Vol 49 (2) ◽  
pp. 135-146 ◽  
Author(s):  
Pekka Pamilo ◽  
Masatoshi Nei ◽  
Wen-Hsiung Li
Keyword(s):  
Weak Selection ◽  
Population Variance ◽  
Asexual Population ◽  
Term Evolution ◽  
A Genome ◽  
Analytical Formulae ◽  
The Mean ◽  
Asexual Populations ◽  
Mutant Genes

SummaryThe accumulation of beneficial and harmful mutations in a genome is studied by using analytical methods as well as computer simulation for different modes of reproduction. The modes of reproduction examined are biparental (bisexual, hermaphroditic), uniparental (selfing, automictic, asexual) and mixed (partial selfing, mixture of hermaphroditism and parthenogenesis). It is shown that the rates of accumulation of both beneficial and harmful mutations with weak selection depend on the within-population variance of the number of mutant genes per genome. Analytical formulae for this variance are derived for neutral mutant genes for hermaphroditic, selfing and asexual populations; the neutral variance is largest in a selfing population and smallest in an asexual population. Directional selection reduces the population variance in most cases, whereas recombination partially restores the reduced variance. Therefore, biparental organisms accumulate beneficial mutations at the highest rate and harmful mutations at the lowest rate. Selfing organisms are intermediate between biparental and asexual organisms. Even a limited amount of outcrossing in largely selfing and parthenogenetic organisms markedly affects the accumulation rates. The accumulation of mutations is likely to affect the mean population fitness only in long-term evolution.

Sex and Adaptation in a Changing Environment

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 1041-1053 ◽  
Author(s):  
David Waxman ◽  
Joel R Peck
Keyword(s):  
Mathematical Model ◽  
Genetic Variability ◽  
Environmental Change ◽  
Natural Populations ◽  
Changing Environment ◽  
Asexual Population ◽  
Sexual Population ◽  
Large Populations ◽  
Stochastic Forces ◽  
Low Rate

Abstract In this study we consider a mathematical model of a sexual population that lives in a changing environment. We find that a low rate of environmental change can produce a very large increase in genetic variability. This may help to explain the high levels of heritability observed in many natural populations. We also study asexuality and find that a modest rate of environmental change can be very damaging to an asexual population, while leaving a sexual population virtually unscathed. Furthermore, in a changing environment, the advantages of sexuality over asexuality can be much greater than suggested by most previous studies. Our analysis applies in the case of very large populations, where stochastic forces may be neglected.

scholarly journals Selection against harmful mutations in large sexual and asexual populations

1982 ◽  
Vol 40 (3) ◽  
pp. 325-332 ◽  
Author(s):  
Alexey S. Kondrashov
Keyword(s):  
Reasonable Assumption ◽  
New Mutation ◽  
Asexual Population ◽  
Sexual Population ◽  
A Genome ◽  
Large Populations ◽  
Asexual Populations ◽  
Average Fitness ◽  
Equilibrium Number ◽  
New Mutations

SUMMARYSelection against harmful mutations in large populations is studied assuming that the rate of fitness decrease grows with every new mutation added to a genome. Under this reasonable assumption (Mayr, 1970) the average fitness of a sexual population, without linkage between the loci, is higher, and the average equilibrium number of harmful mutations per individual lower, than in an asexual population. If a gamete contains on the average one or more new mutations, the resulting advantage of sexual reproduction and recombination seems to be sufficient to counterbalance the double advantage of parthenogenesis. Moreover, selection against harmful mutations is probably the most powerful factor preventing linkage disequilibrium even with epistatic interaction between the loci.

scholarly journals The evolution of latent genes in subdivided populations.

Genetics ◽  
1990 ◽  
Vol 124 (1) ◽  
pp. 187-197
Author(s):  
M E Moody ◽  
C J Basten
Keyword(s):  
Dna Sequences ◽  
Global Dynamics ◽  
Migration Rates ◽  
Wide Range ◽  
The Face ◽  
Subdivided Populations ◽  
Genetic Mechanisms ◽  
And Migration ◽  
Parameter Values ◽  
Insight Into

Abstract We define latent genes as phenotypically silent DNA sequences which may be reactivated by various genetic mechanisms. Of interest is how they and their functional counterparts can be maintained at high frequency in the face of mutation and selection pressure. We propose a two-deme, three-allele model incorporating viability selection, mutation and migration in haploid populations. It is shown that polymorphism for the three alleles can be easily maintained for a wide range of biologically meaningful parameter values. Computer simulations were employed to gain qualitative insight into the global dynamics of the system. It was found that the dynamics of the latent allele is closely correlated with that of the functional allele. In addition, bias in the migration rates can strengthen or weaken selective conditions for preservation of the functional and latent alleles.

Predicting Daily Maintenance Dose of Fluindione, an Oral Anticoagulant Drug

1996 ◽  
Vol 75 (05) ◽  
pp. 731-733 ◽  
Author(s):  
V Cazaux ◽  
B Gauthier ◽  
A Elias ◽  
D Lefebvre ◽  
J Tredez ◽  
...  
Keyword(s):  
Effective Dose ◽  
Maintenance Dose ◽  
Successive Approximations ◽  
Hemorrhagic Complication ◽  
Simple Method ◽  
Individual Variations ◽  
Anticoagulant Drug ◽  
The Mean ◽  
Mean Time ◽  
Daily Maintenance Dose

SummaryDue to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p<0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.

Retrospective analysis of mortality within 30 days of systemic anticancer therapy and comparison with a previous audit at an Australian Regional Cancer Centre

2021 ◽  
pp. 107815522110160
Author(s):  
Bernadatte Zimbwa ◽  
Peter J Gilbar ◽  
Mark R Davis ◽  
Srinivas Kondalsamy-Chennakesavan
Keyword(s):  
Checkpoint Inhibitors ◽  
Anticancer Therapy ◽  
Mortality Rates ◽  
Feedback Process ◽  
Time To Death ◽  
Cancer Centre ◽  
Haematology Patients ◽  
The Mean ◽  
Regional Cancer Centre ◽  
Mean Time

Purpose To retrospectively determine the rate of death occurring within 14 and 30 days of systemic anticancer therapy (SACT), compare this against a previous audit and benchmark results against other cancer centres. Secondly, to determine if the introduction of immune checkpoint inhibitors (ICI), not available at the time of the initial audit, impacted mortality rates. Method All adult solid tumour and haematology patients receiving SACT at an Australian Regional Cancer Centre (RCC) between January 2016 and July 2020 were included. Results Over a 55-month period, 1709 patients received SACT. Patients dying within 14 and 30 days of SACT were 3.3% and 7.0% respectively and is slightly higher than our previous study which was 1.89% and 5.6%. Mean time to death was 15.5 days. Males accounted for 63.9% of patients and the mean age was 66.8 years. 46.2% of the 119 patients dying in the 30 days post SACT started a new line of treatment during that time. Of 98 patients receiving ICI, 22.5% died within 30 days of commencement. Disease progression was the most common cause of death (79%). The most common place of death was the RCC (38.7%). Conclusion The rate of death observed in our re-audit compares favourably with our previous audit and is still at the lower end of that seen in published studies in Australia and internationally. Cases of patients dying within 30 days of SACT should be regularly reviewed to maintain awareness of this benchmark of quality assurance and provide a feedback process for clinicians.

Vitamin D Level Stability in Dystrophinopathy Patients on Vitamin D Supplementation

2021 ◽  
pp. 1-7
Author(s):  
Naomi Vather-Wu ◽  
Matthew D. Krasowski ◽  
Katherine D. Mathews ◽  
Amal Shibli-Rahhal
Keyword(s):  
Vitamin D ◽  
Retrospective Cohort ◽  
Vitamin D Supplementation ◽  
Hydroxyvitamin D ◽  
Frequent Monitoring ◽  
25 Hydroxyvitamin D ◽  
The Mean ◽  
Stable Maintenance ◽  
Mean Time

Background: Expert guidelines recommend annual monitoring of 25-hydroxyvitamin D (25-OHD) and maintaining 25-OHD ≥30 ng/ml in patients with dystrophinopathies. Objective: We hypothesized that 25-OHD remains stable and requires less frequent monitoring in patients taking stable maintenance doses of vitamin D. Methods: We performed a retrospective cohort study, using the electronic health record to identify 26 patients with dystrophinopathies with a baseline 25-OHD ≥30 ng/mL and at least one additional 25-OHD measurement. These patients had received a stable dose of vitamin D for ≥3 months prior to their baseline 25-OHD measurement and throughout follow-up. The main outcome measured was the mean duration time the subjects spent with a 25-OHD ≥30 ng/mL. Results: Only 19% of patients dropped their 25-OHD to <  30 ng/ml, with a mean time to drop of 33 months and a median nadir 25-OHD of 28 ng/mL. Conclusions: These results suggest that measurement of 25-OHD every 2–2.5 years may be sufficient in patients with a baseline 25-OHD ≥30 ng/mL and who are on a stable maintenance dose of vitamin D. Other patients may require more frequent assessments.

scholarly journals Surveillance System in Smart Cities: A Dependability Evaluation Based on Stochastic Models

Electronics ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 876
Author(s):  
Igor Gonçalves ◽  
Laécio Rodrigues ◽  
Francisco Airton Silva ◽  
Tuan Anh Nguyen ◽  
Dugki Min ◽  
...  
Keyword(s):  
Surveillance System ◽  
Smart Cities ◽  
Heterogeneous Data ◽  
Time To Failure ◽  
Video Streams ◽  
Dependability Evaluation ◽  
The Mean ◽  
Mean Time ◽  
The Internet Of Things

Surveillance monitoring systems are highly necessary, aiming to prevent many social problems in smart cities. The internet of things (IoT) nowadays offers a variety of technologies to capture and process massive and heterogeneous data. Due to the fact that (i) advanced analyses of video streams are performed on powerful recording devices; while (ii) surveillance monitoring services require high availability levels in the way that the service must remain connected, for example, to a connection network that offers higher speed than conventional connections; and that (iii) the trust-worthy dependability of a surveillance system depends on various factors, it is not easy to identify which components/devices in a system architecture have the most impact on the dependability for a specific surveillance system in smart cities. In this paper, we developed stochastic Petri net models for a surveillance monitoring system with regard to varying several parameters to obtain the highest dependability. Two main metrics of interest in the dependability of a surveillance system including reliability and availability were analyzed in a comprehensive manner. The analysis results show that the variation in the number of long-term evolution (LTE)-based stations contributes to a number of nines (#9s) increase in availability. The obtained results show that the variation of the mean time to failure (MTTF) of surveillance cameras exposes a high impact on the reliability of the system. The findings of this work have the potential of assisting system architects in planning more optimized systems in this field based on the proposed models.

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