Wolbachia
is an endosymbiotic
Alphaproteobacteria
that can suppress insect-borne diseases through decreasing host virus transmission (population replacement) or through decreasing host population ...density (population suppression). We contrast natural
Wolbachia
infections in insect populations with
Wolbachia
transinfections in mosquitoes to gain insights into factors potentially affecting the long-term success of
Wolbachia
releases. Natural
Wolbachia
infections can spread rapidly, whereas the slow spread of transinfections is governed by deleterious effects on host fitness and demographic factors. Cytoplasmic incompatibility (CI) generated by
Wolbachia
is central to both population replacement and suppression programs, but CI in nature can be variable and evolve, as can
Wolbachia
fitness effects and virus blocking.
Wolbachia
spread is also influenced by environmental factors that decrease
Wolbachia
titer and reduce maternal
Wolbachia
transmission frequency. More information is needed on the interactions between
Wolbachia
and host nuclear mitochondrial genomes, the interaction between invasion success and local ecological factors, and the long-term stability of
Wolbachia
-mediated virus blocking.
Abstract
Adaptation dynamics on fitness landscapes is often studied theoretically in the strong-selection, weak-mutation regime. However, in a large population, multiple beneficial mutants can emerge ...before any of them fixes in the population. Competition between mutants is known as clonal interference, and while it is known to slow down the rate of adaptation (when compared to the strong-selection, weak-mutation model with the same parameters), how it affects the shape of long-term fitness trajectories in the presence of epistasis is an open question. Here, by considering how changes in fixation probabilities arising from weak clonal interference affect the dynamics of adaptation on fitness-parameterized landscapes, we find that the change in the shape of fitness trajectory arises only through changes in the supply of beneficial mutations (or equivalently, the beneficial mutation rate). Furthermore, a depletion of beneficial mutations as a population climbs up the fitness landscape can speed up the rescaled fitness trajectory (where adaptation speed is measured relative to its value at the start of the experiment), while an enhancement of the beneficial mutation rate does the opposite of slowing it down. Our findings suggest that by carrying out evolution experiments in both regimes (with and without clonal interference), one could potentially distinguish the different sources of macroscopic epistasis (fitness effect of mutations vs change in fraction of beneficial mutations).
Aims/hypothesis
The study aimed to quantitatively summarise the dose–response relationships between cardiorespiratory fitness and muscular strength on the one hand and risk of type 2 diabetes on the ...other and estimate the hypothetical benefits associated with population-wide changes in the distribution of fitness.
Methods
We performed a systematic review with meta-analysis. The PubMed and EMBASE electronic databases were searched from inception dates to 12 December 2018 for cohort studies examining the association of cardiorespiratory fitness or muscular strength with risk of incident type 2 diabetes in adults. The quality of included studies was evaluated using the Newcastle–Ottawa Scale.
Results
Twenty-two studies of cardiorespiratory fitness and 13 studies of muscular strength were included in the systematic review with both exposures having ten estimates available for the primary adiposity- or body size-controlled meta-analysis. In random-effects meta-analysis including 40,286 incident cases of type 2 diabetes in 1,601,490 participants, each 1 metabolic equivalent (MET) higher cardiorespiratory fitness was associated with an 8% (95% CI 6%, 10%) lower RR of type 2 diabetes. The association was linear throughout the examined spectrum of cardiorespiratory fitness. In 39,233 cases and 1,713,468 participants each 1 SD higher muscular strength was associated with a 13% (95% CI 6%, 19%) lower RR of type 2 diabetes. We estimated that 4% to 21% of new annual cases of type 2 diabetes among 45–64-year-olds could be prevented by feasible and plausible population cardiorespiratory fitness changes.
Conclusions/interpretation
Relatively small increments in cardiorespiratory fitness and muscle strength were associated with clinically meaningful reductions in type 2 diabetes risk with indication of a linear dose–response relationship for cardiorespiratory fitness.
Registration:
PROSPERO (CRD42017064526).
Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance remains largely ...unknown. Blood sequencing data from ~50,000 individuals reveal how mutation, genetic drift, and fitness shape the genetic diversity of healthy blood (clonal hematopoiesis). We show that positive selection, not drift, is the major force shaping clonal hematopoiesis, provide bounds on the number of hematopoietic stem cells, and quantify the fitness advantages of key pathogenic variants, at single-nucleotide resolution, as well as the distribution of fitness effects (fitness landscape) within commonly mutated driver genes. These data are consistent with clonal hematopoiesis being driven by a continuing risk of mutations and clonal expansions that become increasingly detectable with age.
Cardiorespiratory fitness (CRF) is inversely associated with all-cause mortality. However, the association of CRF and mortality risk for different races, women, and elderly individuals has not been ...fully assessed.
The aim of this study was to evaluate the association of CRF and mortality risk across the spectra of age, race, and sex.
A total of 750,302 U.S. veterans aged 30 to 95 years (mean age 61.3 ± 9.8 years) were studied, including septuagenarians (n = 110,637), octogenarians (n = 26,989), African Americans (n = 142,798), Hispanics (n = 35,197), Native Americans (n = 16,050), and women (n = 45,232). Age- and sex-specific CRF categories (quintiles and 98th percentile) were established objectively on the basis of peak METs achieved during a standardized exercise treadmill test. Multivariable Cox models were used to estimate HRs and 95% CIs for mortality across the CRF categories.
During follow-up (median 10.2 years, 7,803,861 person-years of observation), 174,807 subjects died, averaging 22.4 events per 1,000 person-years. The adjusted association of CRF and mortality risk was inverse and graded across the age spectrum, sex, and race. The lowest mortality risk was observed at approximately 14.0 METs for men (HR: 0.24; 95% CI: 0.23-0.25) and women (HR: 0.23; 95% CI: 0.17-0.29), with no evidence of an increase in risk with extremely high CRF. The risk for least fit individuals (20th percentile) was 4-fold higher (HR: 4.09; 95% CI: 3.90-4.20) compared with extremely fit individuals.
The association of CRF and mortality risk across the age spectrum (including septuagenarians and octogenarians), men, women, and all races was inverse, independent, and graded. No increased risk was observed with extreme fitness. Being unfit carried a greater risk than any of the cardiac risk factors examined.
Temporal variation in natural selection is predicted to strongly impact the evolution and demography of natural populations, with consequences for the rate of adaptation, evolution of plasticity, and ...extinction risk. Most of the theory underlying these predictions assumes a moving optimum phenotype, with predictions expressed in terms of the temporal variance and autocorrelation of this optimum. However, empirical studies seldom estimate patterns of fluctuations of an optimum phenotype, precluding further progress in connecting theory with observations. To bridge this gap, we assess the evidence for temporal variation in selection on breeding date by modeling a fitness function with a fluctuating optimum, across 39 populations of 21 wild animals, one of the largest compilations of long-term datasets with individual measurements of trait and fitness components. We find compelling evidence for fluctuations in the fitness function, causing temporal variation in the magnitude, but not the direction of selection. However, fluctuations of the optimum phenotype need not directly translate into variation in selection gradients, because their impact can be buffered by partial tracking of the optimum by the mean phenotype. Analyzing individuals that reproduce in consecutive years, we find that plastic changes track movements of the optimum phenotype across years, especially in bird species, reducing temporal variation in directional selection. This suggests that phenological plasticity has evolved to cope with fluctuations in the optimum, despite their currently modest contribution to variation in selection.
Abstract
Life-history traits or “fitness components”—such as age and size at maturity, fecundity and fertility, age-specific rates of survival, and life span—are the major phenotypic determinants of ...Darwinian fitness. Analyzing the evolution and genetics of these phenotypic targets of selection is central to our understanding of adaptation. Due to its simple and rapid life cycle, cosmopolitan distribution, ease of maintenance in the laboratory, well-understood evolutionary genetics, and its versatile genetic toolbox, the “vinegar fly” Drosophila melanogaster is one of the most powerful, experimentally tractable model systems for studying “life-history evolution.” Here, I review what has been learned about the evolution and genetics of life-history variation in D. melanogaster by drawing on numerous sources spanning population and quantitative genetics, genomics, experimental evolution, evolutionary ecology, and physiology. This body of work has contributed greatly to our knowledge of several fundamental problems in evolutionary biology, including the amount and maintenance of genetic variation, the evolution of body size, clines and climate adaptation, the evolution of senescence, phenotypic plasticity, the nature of life-history trade-offs, and so forth. While major progress has been made, important facets of these and other questions remain open, and the D. melanogaster system will undoubtedly continue to deliver key insights into central issues of life-history evolution and the genetics of adaptation.
Metabolic equivalents, or METs, are routinely employed as a guide to exercise training and activity prescription and to categorize cardiorespiratory fitness (CRF). There are, however, inherent ...limitations to the concept, as well as common misapplications. CRF and the patient's capacity for physical activity are often overestimated and underestimated, respectively. Moreover, frequently cited fitness thresholds associated with the highest and lowest mortality rates may be misleading, as these are influenced by several factors, including age and gender. The conventional assumption that 1 MET = 3.5 mL O2/kg/min has been challenged in numerous studies that indicate a significant overestimation of actual resting energy expenditure in some populations, including coronary patients, the morbidly obese, and individuals taking β-blockers. These data have implications for classifying relative energy expenditure at submaximal and peak exercise. Heart rate may be used to approximate activity METs, resulting in a promising new fitness metric termed the “personal activity intelligence” or PAI score. Despite some limitations, the MET concept provides a useful method to quantitate CRF and define a repertoire of physical activities that are likely to be safe and therapeutic. In conclusion, for previously inactive adults, moderate-to-vigorous physical activity, which corresponds to ≥3 METs, may increase MET capacity and decrease the risk of future cardiac events.
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