Solving the conundrum of intra-specific variation in metabolic rate: A multidisciplinary conceptual and methodological toolkit: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species: New technical developments are opening the door to an understanding of why metabolic rate varies among individual animals of a species.

Researchers from diverse disciplines, including organismal and cellular physiology, sports science, human nutrition, evolution and ecology, have sought to understand the causes and consequences of the surprising variation in metabolic rate found among and within individual animals of the same species. Research in this area has been hampered by differences in approach, terminology and methodology, and the context in which measurements are made. Recent advances provide important opportunities to identify and address the key questions in the field. By bringing together researchers from different areas of biology and biomedicine, we describe and evaluate these developments and the insights they could yield, highlighting the need for more standardisation across disciplines. We conclude with a list of important questions that can now be addressed by developing a common conceptual and methodological toolkit for studies on metabolic variation in animals.

Differences in the oxidative balance of dispersing and non-dispersing individuals: an experimental approach in a passerine bird.

BACKGROUND: Dispersal is often associated with a suite of phenotypic traits that might reduce dispersal costs, but can be energetically costly themselves outside dispersal. Hence, dispersing and philopatric individuals might differ throughout their life cycle in their management of energy production. Because higher energy expenditure can lead to the production of highly reactive oxidative molecules that are deleterious to the organism if left uncontrolled, dispersing and philopatric individuals might differ in their management of oxidative balance. Here, we experimentally increased flight costs during reproduction via a wing load manipulation in female collared flycatchers (Ficedula albicollis) breeding in a patchy population. We measured the effects of the manipulation on plasmatic markers of oxidative balance and reproductive success in dispersing and philopatric females. RESULTS: The impact of the wing load manipulation on the oxidative balance differed according to dispersal status. The concentration of reactive oxygen metabolites (ROMs), a marker of pro-oxidant status, was higher in philopatric than dispersing females in the manipulated group only. Differences between dispersing and philopatric individuals also depended on habitat quality, as measured by local breeding density. In low quality habitats, ROMs as well as nestling body mass were higher in philopatric females compared to dispersing ones. Independently of the manipulation or of habitat quality, plasma antioxidant capacity differed according to dispersal status: philopatric females showed higher antioxidant capacity than dispersing ones. Nestlings raised by philopatric females also had a higher fledging success. CONCLUSIONS: Our results suggest that dispersing individuals maintain a stable oxidative balance when facing challenging environmental conditions, at the cost of lower reproductive success. Conversely, philopatric individuals increase their effort, and thus oxidative costs, in challenging conditions thereby maintaining their reproductive success. Our study sheds light on energetics and oxidative balance as possible processes underlying phenotypic differences between dispersing and philopatric individuals.

Food supplementation mitigates dispersal-dependent differences in nest defence in a passerine bird.

Dispersing and non-dispersing individuals often differ in phenotypic traits (e.g. physiology, behaviour), but to what extent these differences are fixed or driven by external conditions remains elusive. We experimentally tested whether differences in nest-defence behaviour between dispersing and non-dispersing individuals changed with local habitat quality in collared flycatchers, by providing additional food during the nestling rearing period. In control (non-food-supplemented) nests, dispersers were less prone to defend their brood compared with non-dispersers, whereas in food-supplemented nests, dispersing and non-dispersing individuals showed equally strong nest defence. We discuss the importance of dispersal costs versus adaptive flexibility in reproductive investment in shaping these differences in nest-defence behaviour between dispersing and non-dispersing individuals. Irrespective of the underlying mechanisms, our study emphasizes the importance of accounting for environmental effects when comparing traits between dispersing and non-dispersing individuals, and in turn assessing the costs and benefits of dispersal.

Selective disappearance of individuals with high levels of glycated haemoglobin in a free-living bird.

Although disruption of glucose homeostasis is a hallmark of ageing in humans and laboratory model organisms, we have little information on the importance of this process in free-living animals. Poor control of blood glucose levels leads to irreversible protein glycation. Hence, levels of protein glycation are hypothesized to increase with age and to be associated with a decline in survival. We tested these predictions by measuring blood glycated haemoglobin in 274 adult collared flycatchers of known age and estimating individual probability of recapture in the following 2 years. Results show a strong decrease in glycated haemoglobin from age 1 to 5 years and an increase thereafter. Individuals with high levels of glycated haemoglobin had a lower probability of recapture, even after controlling for effects of age and dispersal. Altogether, our findings suggest that poor control of glucose homoeostasis is associated with lower survival in this free-living bird population, and that the selective disappearance of individuals with the highest glycation levels could account for the counterintuitive age-related decline in glycated haemoglobin in the early age categories.

Resource and seasonality drive interspecific variability in simulations from a dynamic energy budget model.

Animals show a vast array of phenotypic traits in time and space. Such variation patterns have traditionally been described as ecogeographical rules; for example, the tendency of size and clutch size to increase with latitude (Bergmann's and Lack's rules, respectively). Despite considerable research into these variation patterns and their consequences for biodiversity and conservation, the processes behind trait variation remain controversial. Here, we show how food variability, largely set by climate and weather, can drive interspecific trait variation by determining individual energy input and allocation trade-offs. Using a dynamic energy budget (DEB) model, we simulated different food environments, as well as interspecific variability in the parameters for energy assimilation, mobilization and allocation to soma. We found that interspecific variability is greater when the resource is non-limiting in both constant and seasonal environments. Our findings further show that individuals can reach larger biomass and greater reproductive output in a seasonal environment than in a constant environment of equal average resource due to the peaks of food surplus. Our results agree with the classical patterns of interspecific trait variation and provide a mechanistic understanding that supports recent hypotheses which explain them: the resource and the eNPP (net primary production during the growing season) rules. Due to the current alterations to ecosystems and communities, disentangling the mechanisms of trait variation is increasingly important to understand and predict biodiversity dynamics under climate change, as well as to improve conservation strategies.

The Cytidine Deaminase APOBEC3G Contributes to Cancer Mutagenesis and Clonal Evolution in Bladder Cancer.

Mutagenic processes leave distinct signatures in cancer genomes. The mutational signatures attributed to APOBEC3 cytidine deaminases are pervasive in human cancers. However, data linking individual APOBEC3 proteins to cancer mutagenesis in vivo are limited. Here, we showed that transgenic expression of human APOBEC3G promotes mutagenesis, genomic instability, and kataegis, leading to shorter survival in a murine bladder cancer model. Acting as mutagenic fuel, APOBEC3G increased the clonal diversity of bladder cancer, driving divergent cancer evolution. Characterization of the single-base substitution signature induced by APOBEC3G in vivo established the induction of a mutational signature distinct from those caused by APOBEC3A and APOBEC3B. Analysis of thousands of human cancers revealed the contribution of APOBEC3G to the mutational profiles of multiple cancer types, including bladder cancer. Overall, this study dissects the mutagenic impact of APOBEC3G on the bladder cancer genome, identifying that it contributes to genomic instability, tumor mutational burden, copy-number loss events, and clonal diversity. SIGNIFICANCE: APOBEC3G plays a role in cancer mutagenesis and clonal heterogeneity, which can potentially inform future therapeutic efforts that restrict tumor evolution. See related commentary by Caswell and Swanton, p. 487.

Antioxidant capacity is repeatable across years but does not consistently correlate with a marker of peroxidation in a free-living passerine bird.

Oxidative stress occurs when reactive oxygen species (ROS) exceed antioxidant defences, which can have deleterious effects on cell function, health and survival. Therefore, organisms are expected to finely regulate pro-oxidant and antioxidant processes. ROS are mainly produced through aerobic metabolism and vary in response to changes in energetic requirements, whereas antioxidants may be enhanced, depleted or show no changes in response to changes in ROS levels. We investigated the repeatability, within-individual variation and correlation across different conditions of two plasmatic markers of the oxidative balance in 1108 samples from 635 free-living adult collared flycatchers (Ficedula albicollis). We sought to manipulate energy constraints by increasing wing load in 2012 and 2013 and by providing additional food in 2014. We then tested the relative importance of within- and between-individual variation on reactive oxygen metabolites (ROMs), a marker of lipid and protein peroxidation, and on non-enzymatic antioxidant defences (OXY test). We also investigated whether the experimental treatments modified the correlation between markers. Antioxidant defences were repeatable (range of repeatability estimates = 0.128-0.581), whereas ROMs were not (0-0.061). Antioxidants varied neither between incubation and nestling feeding nor between sexes. ROMs increased from incubation to nestling feeding in females and were higher in females than males. Antioxidant defences and ROM concentration were globally positively correlated, but the correlation varied between experimental conditions and between years. Hence, the management of oxidative balance in wild animals appears flexible under variable environmental conditions, an observation which should be confirmed over a wider range of markers.