scholarly journals Deleterious mutations show increasing negative effects with age in Drosophila melanogaster

BMC Biology ◽  
2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Martin I. Brengdahl ◽  
Christopher M. Kimber ◽  
Phoebe Elias ◽  
Josephine Thompson ◽  
Urban Friberg
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Architecture ◽  
Deleterious Mutations ◽  
Negative Effects ◽  
Evolutionary Theories ◽  
Theories Of Aging ◽  
Specific Effects ◽  
Rate Of Increase ◽  
Negative Effect ◽  
Evolution Of Aging

Abstract Background In order for aging to evolve in response to a declining strength of selection with age, a genetic architecture that allows for mutations with age-specific effects on organismal performance is required. Our understanding of how selective effects of individual mutations are distributed across ages is however poor. Established evolutionary theories assume that mutations causing aging have negative late-life effects, coupled to either positive or neutral effects early in life. New theory now suggests evolution of aging may also result from deleterious mutations with increasing negative effects with age, a possibility that has not yet been empirically explored. Results To directly test how the effects of deleterious mutations are distributed across ages, we separately measure age-specific effects on fecundity for each of 20 mutations in Drosophila melanogaster. We find that deleterious mutations in general have a negative effect that increases with age and that the rate of increase depends on how deleterious a mutation is early in life. Conclusions Our findings suggest that aging does not exclusively depend on genetic variants assumed by the established evolutionary theories of aging. Instead, aging can result from deleterious mutations with negative effects that amplify with age. If increasing negative effect with age is a general property of deleterious mutations, the proportion of mutations with the capacity to contribute towards aging may be considerably larger than previously believed.

scholarly journals Evolution favors aging in populations with assortative mating and strong pathogen pressure

2018 ◽  
Author(s):  
Peter Lenart ◽  
Julie Bienertová-Vašků ◽  
Luděk Berec
Keyword(s):  
Mathematical Model ◽  
Assortative Mating ◽  
Mating Pattern ◽  
Evolutionary Theories ◽  
The Past ◽  
Theories Of Aging ◽  
Aging Program ◽  
Evolution Of Aging ◽  
Insight Into

AbstractSince at first sight aging seems to be omnipresent, many authors to this very day regard it as an inevitable consequence of the laws of physics. However, studies published in the past two decades have conclusively shown that a number of organisms do not age, or at least do not age on a scale comparable with other aging organisms. This disparity leads us to question why aging evolved in some organisms and not in others. We thus present a mathematical model which simulates evolution in a sexually reproducing population composed of aging and non-aging individuals. We have observed that aging individuals may outcompete non-aging individuals if they have a higher starting fertility or if the main mating pattern in the population is assortative mating. Furthermore, stronger pathogen pressure was found to help the aging phenotype when compared to the non-aging phenotype. Last but not least, the aging phenotype was found to more easily outcompete the non-aging one or to resist the dominance of the latter for a longer period of time in populations composed of dimorphic sexually reproducing individuals compared to populations of hermaphrodites. Our findings are consistent with both classical evolutionary theories of aging and with evolutionary theories of aging which assume the existence of an aging program. They can thus potentially work as a bridge between these two opposing views, suggesting that the truth in fact lies somewhere in between.Significance StatementThis study presents the first mathematical model which simulates the evolution of aging in a population of sexually reproducing organisms. Our model shows that aging individuals may outcompete non-aging individuals in several scenarios known to occur in nature. Our work thus provides important insight into the question why aging has evolved in most, but not all, organisms.

scholarly journals Mutational and Selective Processes Involved in Evolution during Bacterial Range Expansions

2019 ◽  
Vol 36 (10) ◽  
pp. 2313-2327 ◽  
Author(s):  
Lars Bosshard ◽  
Stephan Peischl ◽  
Martin Ackermann ◽  
Laurent Excoffier
Keyword(s):  
Gene Expression ◽  
Artificial Selection ◽  
Colony Size ◽  
Deleterious Mutations ◽  
Loss Of Function ◽  
Negative Effects ◽  
Bacterial Populations ◽  
Fast Expansions ◽  
Negative Effect ◽  
Expansion Load

AbstractBacterial populations have been shown to accumulate deleterious mutations during spatial expansions that overall decrease their fitness and ability to grow. However, it is unclear if and how they can respond to selection in face of this mutation load. We examine here if artificial selection can counteract the negative effects of range expansions. We examined the molecular evolution of 20 mutator lines selected for fast expansions (SEL) and compared them to 20 other mutator lines freely expanding without artificial selection (CONTROL). We find that the colony size of all 20 SEL lines have increased relative to the ancestral lines, unlike CONTROL lines, showing that enough beneficial mutations are produced during spatial expansions to counteract the negative effect of expansion load. Importantly, SEL and CONTROL lines have similar numbers of mutations indicating that they evolved for the same number of generations and that increased fitness is not due to a purging of deleterious mutations. We find that loss of function mutations better explain the increased colony size of SEL lines than nonsynonymous mutations or a combination of the two. Interestingly, most loss of function mutations are found in simple sequence repeats (SSRs) located in genes involved in gene regulation and gene expression. We postulate that such potentially reversible mutations could play a major role in the rapid adaptation of bacteria to changing environmental conditions by shutting down expensive genes and adjusting gene expression.

scholarly journals The Danaid Theory of Aging

2022 ◽  
Vol 9 ◽  
Author(s):  
Maarten J. Wensink ◽  
Alan A. Cohen
Keyword(s):  
Selection Pressure ◽  
Evolutionary Theories ◽  
Complex Systems Theory ◽  
Selective Pressures ◽  
Theories Of Aging ◽  
Trade Offs ◽  
Chance Events ◽  
Theory Of Aging ◽  
Evolution Of Aging ◽  
Complex Forms

The classical evolutionary theories of aging suggest that aging evolves due to insufficient selective pressure against it. In these theories, declining selection pressure with age leads to aging through genes or resource allocations, implying that aging could potentially be stalled were genes, resource allocation, or selection pressure somewhat different. While these classical evolutionary theories are undeniably part of a description of the evolution of aging, they do not explain the diversity of aging patterns, and they do not constitute the only possible evolutionary explanation. Without denying selection pressure a role in the evolution of aging, we argue that the origin and diversity of aging should also be sought in the nature and evolution of organisms that are, from their very physiological make up, unmaintainable. Drawing on advances in developmental biology, genetics, biochemistry, and complex systems theory since the classical theories emerged, we propose a fresh evolutionary-mechanistic theory of aging, the Danaid theory. We argue that, in complex forms of life like humans, various restrictions on maintenance and repair may be inherent, and we show how such restrictions are laid out during development. We further argue that there is systematic variation in these constraints across taxa, and that this is a crucial factor determining variation in aging and lifespan across the tree of life. Accordingly, the core challenge for the field going forward is to map and understand the mosaic of constraints, trade-offs, chance events, and selective pressures that shape aging in diverse ways across diverse taxa.

scholarly journals Asthma patients experience increased symptoms of anxiety, depression and fear during the COVID-19 pandemic

2021 ◽  
Vol 18 ◽  
pp. 147997312110296
Author(s):  
Geertje M de Boer ◽  
Laura Houweling ◽  
Rudi W Hendriks ◽  
Jan H Vercoulen ◽  
Gerdien A Tramper-Stranders ◽  
...  
Keyword(s):  
Online Survey ◽  
Anxiety And Depression ◽  
Negative Effects ◽  
Cross Sectional ◽  
Healthcare Facilities ◽  
Care Workers ◽  
Asthma Patients ◽  
Negative Effect ◽  
Patients Experience ◽  
Anxiety Depression

Population studies showed a decrease in psychological wellbeing during the COVID-19 pandemic. Asthma is associated with a negative effect on anxiety and depression, which might worsen during the COVID-19 lockdown. The aim of the study was to compare fear, anxiety and depression between asthma patients and patients wit hout asthma pre-COVID-19 and during COVID-19 pandemic. This study compares fear, anxiety and depression in asthma patients and controls between pre-COVID-19 and during COVID-19 lockdown with a cross-sectional online survey. Participants were invited to fill out several questionnaires pertaining to fear, anxiety, depression, asthma control and quality of life. Asthma patients (N = 37) displayed, during the course of the pandemic, a clinically relevant increase in anxiety (3.32 ± 2.95 vs. 6.68 ± 3.78; p < 0.001) and depression (1.30 ± 1.15 vs. 3.65 ± 3.31; p < 0.001), according to the hospital anxiety and depression levels (HADS) compared to pre-COVID-19 assessment. This was not seen in controls. Also, asthma patients displayed more anxiety about acquiring COVID-19 disease compared to controls ((5.11 ± 1.99 vs. 3.50 ± 2.79), p = 0.006). Patients with asthma experienced an increase in anxiety and depression levels and were more afraid of acquiring COVID-19 disease compared to controls. Also, patients with asthma were more likely to avoid healthcare facilities due to fear of acquiring COVID-19 disease compared to controls. Therefore, we advise health care workers to address these possible negative effects on mental health by phone or e-consults.

scholarly journals Impact of “non-lethal” tarsal clipping on bumble bees (Bombus vosnesenskii) may depend on queen stage and worker size

2021 ◽  
Author(s):  
John M. Mola ◽  
Clara Stuligross ◽  
Maureen L. Page ◽  
Danielle Rutkowski ◽  
Neal M. Williams
Keyword(s):  
Genetic Material ◽  
Population Monitoring ◽  
First Year ◽  
Negative Effects ◽  
Worker Size ◽  
Monitoring Tools ◽  
Individual Survival ◽  
Body Sizes ◽  
Negative Effect ◽  
Worker Caste

Abstract Recent bumble bee declines have prompted the development of novel population monitoring tools, including the use of putatively non-lethal tarsal clipping to obtain genetic material. However, the potential side effects of tarsal clipping have only been tested in the worker caste of a single domesticated species, prompting the need to more broadly test whether tarsal clipping negatively affects sampled individuals. To determine if tarsal clipping reduces queen survivorship and colony establishment, we collected wild queens of Bombus vosnesenskii and clipped tarsi from a single leg of half the individuals. We reared captive queens and estimated survivorship and nest establishment success. We also clipped tarsi of workers from a subset of colonies across a range of body sizes. We found no consistent negative effect of clipping on queen survival. In the first year, clipped nest-searching queens suffered heavy mortality, but there was no effect on foraging queens. The following year, we found no effect of clipping on queen survival or establishment. Clipping did not reduce overall worker survival but reduced survivorship for those in the smallest size quartile. Implications for insect conservation Our findings suggest tarsal clipping does not have consistent negative effects on individual survival. However, our results varied with queen behavioral state, year, and worker size, suggesting differences within and among species and interactions with landscape stressors warrant further study. In the interim, we recommend researchers and conservationists minimize the use of tarsal clipping for sensitive species, populations, or small workers except in cases of exceptional scientific need.

scholarly journals The Rate of Mutation and the Homozygous and Heterozygous Mutational Effects for Competitive Viability: A Long-Term Experiment With Drosophila melanogaster

Genetics ◽  
2001 ◽  
Vol 158 (2) ◽  
pp. 681-693 ◽  
Author(s):  
David Chavarrías ◽  
Carlos López-Fanjul ◽  
Aurora García-Dorado
Keyword(s):  
Drosophila Melanogaster ◽  
Minimum Distance ◽  
Deleterious Mutations ◽  
Regression Estimate ◽  
Term Experiment ◽  
Degree Of Dominance ◽  
Long Term Experiment ◽  
Rate Of Decline ◽  
Good Agreement

Abstract The effect of 250 generations of mutation accumulation (MA) on the second chromosome competitive viability of Drosophila melanogaster was analyzed both in homozygous and heterozygous conditions. We used full-sib MA lines, where selection hampers the accumulation of severely deleterious mutations but is ineffective against mildly deleterious ones. A large control population was simultaneously evaluated. Competitive viability scores, unaffected by the expression of mutations in heterozygosis, were obtained relative to a Cy/L2 genotype. The rate of decline in mean ΔM ≈ 0.1% was small. However, that of increase in variance ΔV ≈ 0.08 × 10-3 was similar to the values obtained in previous experiments when severely deleterious mutations were excluded. The corresponding estimates of the mutation rate λ ≥ 0.01 and the average effect of mutations E(s) ≤ 0.08 are in good agreement with Bateman-Mukai and minimum distance estimates for noncompetitive viability obtained from the same MA lines after 105 generations. Thus, competitive and noncompetitive viability show similar mutational properties. The regression estimate of the degree of dominance for mild-to-moderate deleterious mutations was ∼0.3, suggesting that the pertinent value for new unselected mutations should be somewhat smaller.

scholarly journals Long-term subjective memory after electroconvulsive therapy

BJPsych Open ◽  
2020 ◽  
Vol 6 (2) ◽  
Author(s):  
Robert Sigström ◽  
Axel Nordenskjöld ◽  
Anders Juréus ◽  
Caitlin Clements ◽  
Erik Joas ◽  
...  
Keyword(s):  
Electroconvulsive Therapy ◽  
Memory Impairment ◽  
Rating Scale ◽  
Final Analysis ◽  
Negative Effects ◽  
Subjective Memory ◽  
Subjective Memory Impairment ◽  
Negative Effect ◽  
Negative Expectations

Background There have been reports of long-term subjective memory worsening after electroconvulsive therapy (ECT). Aims To study the prevalence and risk factors of long-term subjective memory worsening among patients receiving ECT in routine clinical practice. Method Patients (n = 535, of whom 277 were included in the final analysis) were recruited from eight Swedish hospitals. Participants' subjective memory impairment was assessed before ECT and a median of 73 days after ECT using the memory item from the Comprehensive Psychopathological Rating Scale. Participants also rated their pre-ECT expectations and post-ECT evaluations of the effect of ECT on memory on a 7-point scale. We used ordinal regression to identify variables associated with subjective memory worsening and negative evaluations of the effect of ECT on memory. Results Comparisons of pre- and post-ECT assessments showed that subjective memory worsened in 16.2% of participants, remained unchanged in 52.3% and improved in 31.4%. By contrast, when asked to evaluate the effect of ECT on memory after treatment 54.6% reported a negative effect. Subjective memory worsening was associated with negative expectations before ECT, younger age and shorter duration of follow-up. Conclusions Although subjective memory improved more often than it worsened when assessed before and after ECT, a majority of patients reported that ECT had negative effects on their memory when retrospectively asked how ECT had affected it. This might suggest that some patients attribute pre-existing subjective memory impairment to ECT. Clinicians should be aware that negative expectations are associated with subjective worsening of memory after ECT.

scholarly journals Dominant Negative Mutants Implicate STAT5 in Myeloid Cell Proliferation and Neutrophil Differentiation

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4154-4166 ◽  
Author(s):  
Robert L. Ilaria ◽  
Robert G. Hawley ◽  
Richard A. Van Etten
Keyword(s):  
Dna Binding ◽  
Transcriptional Activation ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Cytokine Signaling ◽  
Transactivation Domain ◽  
Negative Effects ◽  
Murine Bone Marrow ◽  
Negative Effect

Abstract STAT5 is a member of the signal transducers and activation of transcription (STAT) family of latent transcription factors activated in a variety of cytokine signaling pathways. We introduced alanine substitution mutations in highly conserved regions of murine STAT5A and studied the mutants for dimerization, DNA binding, transactivation, and dominant negative effects on erythropoietin-induced STAT5-dependent transcriptional activation. The mutations included two near the amino-terminus (W255KR→AAA and R290QQ→AAA), two in the DNA-binding domain (E437E→AA and V466VV→AAA), and a carboxy-terminal truncation of STAT5A (STAT5A/▵53C) analogous to a naturally occurring isoform of rat STAT5B. All of the STAT mutant proteins were tyrosine phosphorylated by JAK2 and heterodimerized with STAT5B except for the WKR mutant, suggesting an important role for this region in STAT5 for stabilizing dimerization. The WKR, EE, and VVV mutants had no detectable DNA-binding activity, and the WKR and VVV mutants, but not EE, were defective in transcriptional induction. The VVV mutant had a moderate dominant negative effect on erythropoietin-induced STAT5 transcriptional activation, which was likely due to the formation of heterodimers that are defective in DNA binding. Interestingly, the WKR mutant had a potent dominant negative effect, comparable to the transactivation domain deletion mutant, ▵53C. Stable expression of either the WKR or ▵53C STAT5 mutants in the murine myeloid cytokine-dependent cell line 32D inhibited both interleukin-3–dependent proliferation and granulocyte colony-stimulating factor (G-CSF)–dependent differentiation, without induction of apoptosis. Expression of these mutants in primary murine bone marrow inhibited G-CSF–dependent granulocyte colony formation in vitro. These results demonstrate that mutations in distinct regions of STAT5 exert dominant negative effects on cytokine signaling, likely through different mechanisms, and suggest a role for STAT5 in proliferation and differentiation of myeloid cells.

scholarly journals The Psychology of Sharing: Multigroup Analysis among Users and Non-Users of Carsharing

2021 ◽  
Vol 13 (12) ◽  
pp. 6842
Author(s):  
Érika Martins Silva Ramos ◽  
Cecilia Jakobsson Bergstad
Keyword(s):  
Travel Behavior ◽  
Psychological Factors ◽  
Structural Equation ◽  
Subjective Norms ◽  
Equation Modeling ◽  
Intention To Use ◽  
Negative Effects ◽  
Confirmatory Factor ◽  
Negative Effect ◽  
Multigroup Confirmatory Factor Analysis

The present study investigates the determinants of intention to use carsharing services by an integrated model of psychological predictors of travel behavior. The model proposed is tested by multigroup confirmatory factor analysis (MGCFA) in structural equation modeling (SEM) with further discussion about analysis of invariance and its relevance for comparisons between groups. The sample was classified into four groups: Italian users, Italian non-users, Swedish users, and Swedish non-users of carsharing. The users were respondents who have used or are currently using carsharing, while non-users reported never using the carsharing services. The analysis of data from 6072 respondents revealed that control was the main predictor of intention to use carsharing; driving habits had stronger negative effects for users of carsharing than for non-users; subjective norms positively predicted the intention to use carsharing among all groups; trust was a predictor of intention only for the Italian groups; and climate morality had a small negative effect on the Swedish groups only. The outcomes of this investigation will increase the knowledge about the use of carsharing and help to identify the behavioral and psychological factors that primarily influence people’s intention to use it.

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