Biology subjects

Mirth, C.

Publications and source records attributed to Mirth, C..

11 recordsLinked to original sources

bioRxiv2025

Dietary Zn governs protein: carbohydrate regulation of fecundity and lifespan in Drosophila melanogaster

Recent work has shown that dietary zinc (Zn) restriction has a strong effect to limit egg production in female Drosophila, while also producing a variable, but beneficial, effect on lifespan. This combination of phenotypes is interesting because it is consistent with the disposable soma theory of ageing, and phenocopies the well-studied effects of reducing the dietary protein-to-carbohydrate (P:C) ratio. Thus, Zn restriction may be a key precision nutrition intervention to extend lifespan. To investigate this, we decided to assess the interactive effects of dietary Zn and P:C ratios on reproduction and lifespan. We found that the interventions interact, producing equally strong, but not additive, effects to modify female reproduction and lifespan. Specifically, both Zn restriction and lowering the P:C ratio reduced reproduction and benefited lifespan, but only when the other nutrient was maintained at high levels. When either Zn or P:C was at intermediate or low levels, adjusting the other nutritional component varied reproduction, but did so independently of lifespan, which remained fixed at a high level. Disrupting the Zn transporter, white, modified the magnitude of some effects, but not their direction. Thus, the micronutrient Zn modifies life-history outcomes to the same extent as altering the macronutrient (P:C) ratio, indicating its nutritional availability is likely to be a key determinant of fitness for Drosophila.

evolutionary biology↗

bioRxiv2024

Dietary zinc limitation dictates lifespan and reproduction trade-offs of Drosophila mothers

Dietary metal ions significantly influence the lifespan and reproduction of Drosophila females. In this study, we show that while the depletion of all metal ions from the diet adversely affects reproduction and lifespan, the absence of Zn alone negatively impacts reproduction without adversely altering maternal lifespan, indicating it can dictate resource reallocation between key fitness traits. Although our data show that flies sense varying dietary Zn levels, they apparently do not alter their feeding preferences to optimise egg production when faced with a choice between Zn- depleted or Zn- sufficient food, but they can choose to preferentially oviposit on Zn containing food, perhaps indicating a strategy to assure offspring survival. We also uncovered a role for the white gene in sustaining high levels of egg viability when Zn is diluted in the diet. These insights into the role of dietary metal ions, particularly Zn, point to a central role for these dietary micronutrients to indicate environmental quality and so govern trade-offs between lifespan and reproduction in flies.

evolutionary biology↗

bioRxiv2024

Experimental evolution under combined thermal-nutritional stress in Drosophila melanogaster results in evolved shifts in larval thermotolerance and thermal plasticity

Animals commonly face combinations of thermal and nutritional stress in nature, which will intensify under climate change. While genetic adaptation is necessary to buffer long-term stress, its unclear whether adaptation to combined stress can occur without compromising viability and thermal plasticity. We tested larval thermotolerance and thermal plasticity in Drosophila melanogaster selected under different temperatures (18{degrees}C, 25{degrees}C, and 28{degrees}C) and diets (standard, diluted, and low-protein:high-carbohydrate [P:C]). Basal larval cold tolerance was affected by both protein concentration and temperature; larvae evolved higher basal cold tolerance on the diluted and low P:C diets at 18{degrees}C and 28{degrees}C. Hardening increased cold tolerance for most lines, except those selected at 18{degrees}C and 28{degrees}C on low P:C diets and at 25{degrees}C on standard diets. Basal larval heat tolerance was affected by selection temperature; selection at 25{degrees}C increased heat tolerance. An interaction between selection temperature, selection diet, and hardening treatment affected larval heat tolerance; hardening reduced heat tolerance in most lines, except those selected at 25{degrees}C on low P:C diets and at 28{degrees}C on standard diets. Our results suggest that adaptation to combined stress allows basal cold tolerance and its plasticity to co-evolve, but not heat tolerance, highlighting ectotherms vulnerability to long-term climate change.

evolutionary biology↗

bioRxiv2023

Variation in plasticity in response to combined thermal-nutritional stress is genetically independent between sexes and across traits

Phenotypic plasticity helps animals to buffer the effects of increasing thermal and nutritional stress created by climate change. Plastic responses to single and combined stressors can vary among genetically diverged populations. However, less is known about how plasticity in response to combined stress varies among individuals within a population or whether such variation changes across life-history traits. This is important because individual variation within populations shapes population-level responses to environmental change. Here, we used isogenic lines of Drosophila melanogaster to assess plasticity of egg-to-adult viability and sex-specific body size for combinations of two temperatures (25{degrees}C or 28{degrees}C) and three diets (standard diet, low caloric diet, or low protein:carbohydrate ratio diet). Our results reveal substantial within-population genetic variation in plasticity for egg-to-adult viability and wing size in response to combined thermal-nutritional stress. This genetic variation in plasticity was a result of cross-environment genetic correlations that were often < 1 for both traits, as well as changes in the expression of genetic variation across environments for egg-to-adult viability. Cross-sex genetic correlations for body size were weaker when the sexes were reared in different conditions, suggesting that the genetic basis of traits may change with the environment. Further, our results suggest that plasticity in egg-to-adult viability is genetically independent from plasticity in body size. Importantly, plasticity in response to diet and temperature individually differed from plastic shifts in response to diet and temperature in combination. By quantifying plasticity and the expression of genetic variance in response to combined stress across traits, our study reveals the complexity of animal responses to environmental change, and the need for a more nuanced understanding of the potential for populations to adapt to ongoing climate change.

evolutionary biology↗

bioRxiv2021

Nutrigonometry I: using right-angle triangles to quantify nutritional trade-offs in multidimensional performance landscapes

Animals regulate their diet in order to maximise the expression of fitness traits that often have different nutritional needs. These nutritional trade-offs have been experimentally uncovered using the Geometric framework for nutrition (GF). However, current analytical methods to measure such responses rely on either visual inspection or complex models applied to multidimensional performance landscapes, making these approaches subjective, or conceptually difficult, computationally expensive, and in some cases inaccurate. This limits our ability to understand how animal nutrition evolved to support life-histories within and between species. Here, we introduce a simple trigonometric model to measure nutritional trade-offs in multidimensional landscapes ( Nutrigonometry). Nutrigonometry is both conceptually and computationally easier than current approaches, as it harnesses the trigonometric relationships of right-angle triangles instead of vector calculations. Using landmark GF datasets, we first show how polynomial (Bayesian) regressions can be used for precise and accurate predictions of peaks and valleys in performance landscapes, irrespective of the underlying structure of the data (i.e., individual food intakes vs fixed diet ratios). Using trigonometric relationships, we then identified the known nutritional trade-off between lifespan and reproductive rate both in terms of nutrient balance and concentration. Nutrigonometry enables a fast, reliable and reproducible quantification of nutritional trade-offs in multidimensional performance landscapes, thereby broadening the potential for future developments in comparative research on the evolution of animal nutrition.

evolutionary biology↗

bioRxiv2021

The Biosynthetic Costs of Amino Acids at the Base of the Food Chain Determine Their Use in Higher-order Consumer Genomes

Dietary nutrient composition is essential for shaping important fitness traits and behaviours. Many organisms are protein limited and for Drosophila melanogaster, this limitation manifests at the level of the single most limiting essential Amino Acid (AA) in the diet. The identity of this AA and its effects on female fecundity is readily predictable by a procedure called exome matching in which the sum of AAs encoded by a consumers exome is used to predict the relative proportion of AAs required in its diet. However, the exome matching calculation does not weight AA contributions to the overall profile by protein size or expression. Here we update the exome matching calculation to include these weightings. Surprisingly, although nearly half of the transcriptome is differentially expressed when comparing male and female flies, we found that creating transcriptome-weighted exome matched diets for each sex did not enhance their fecundity over that supported by exome matching alone. These data indicate that while organisms may require different amounts of dietary protein across conditions, the relative proportion of the constituent AAs remains constant. Interestingly, we also found remarkable conservation of exome matched AA profiles across taxa and that the composition of these profiles could be explained by the metabolic costs of microbial AA synthesis. Thus, it appears that bioenergetic constraints amongst autotrophs shape the relative proportion of AAs that are available across trophic levels and that that this constrains biomass composition.

genomics↗

bioRxiv2021

Restricting a single amino acid cross-protects D. melanogaster from nicotine poisoning through mTORC1 and GCN2 signalling.

Dietary interventions that restrict protein intake have repeatedly been shown to offer beneficial health outcomes to the consumer. Benefits such as increased stress tolerance can be observed in response to restricting individual amino acids, thus mimicking dietary protein restriction. Here, we sought to further understand the relationship between dietary amino acids and stress tolerance using Drosophila melanogaster. Utilising a chemically defined medium for Drosophila, we found that transiently restricting adult flies of a single essential amino acid generally protects against a lethal dose of the naturally occurring insecticide, nicotine. This protection was conferred during the pre-treatment window, was specific for individual amino acids and depended on the identity of the focal amino acid, as well as the duration and intensity of its restriction. For instance, complete isoleucine deprivation for 7 days maximised its protective effect - increasing survival during nicotine exposure by 100%. However, a dose of 25% threonine was required to maximise its protective effect (53% enhanced survival). To understand the molecular basis of these effects, we modified the signalling of two cellular sensors of amino acids, GCN2 (General control non-derepressible) and mTORC1 (mechanistic Target of Rapamycin Complex 1) in combination with amino acid restriction. We found that GCN2 was necessary for diets to protect against nicotine, whereas suppression of mTORC1 was sufficient to induce nicotine resistance. This finding implies that amino acid restriction acts via amino acid signalling to cross-protect against seemingly unrelated stressors. Altogether, our study offers new insights into the physiological responses to restriction of individual amino acids that confer stress tolerance. This has broad potential for application in animal and human health.

genetics↗

bioRxiv2021

Drosophila melanogaster females prioritise dietary sterols for producing high quality eggs

Limiting calories or specific nutrients without malnutrition, otherwise known as dietary restriction (DR), has been shown to extend lifespan across a broad range of taxa. Our recent findings in Drosophila melanogaster show that supplementing flies on macronutrient-rich diets with additional cholesterol can extend lifespan to the same extent as DR. Macronutrient-rich diets drive high levels of egg production and in doing so deplete the mothers of somatic sterols that are essential for survival. Thus, DR may be beneficial for lifespan because it reduces egg production which in turn reduces the mothers demand for sterols. If this is true, mothers must be prioritising their available sterols, whether from the diet or from their own bodies, to sustain high quality egg production. To test this, we measured the quality of eggs laid by mothers fed either cholesterol-sufficient or cholesterol-depleted diets. We found that even when the mothers diet was completely devoid of cholesterol, high quality egg production persisted. Furthermore, we show that sterol-supplemented flies with long lives continue to lay high quality eggs that give rise to healthy offspring. Thus, in our assays, long life does not require a fecundity cost.

evolutionary biology↗

bioRxiv2020

Ecdysone coordinates plastic growth with robust pattern in the developing wing

Animals develop in unpredictable, variable environments. In response to environmental change some aspects of development adjust to generate plastic phenotypes. Other aspects of development, however, are buffered against environmental change to produce robust phenotypes. How organ development is coordinated to accommodate both plastic and robust developmental responses is poorly understood. Here, we demonstrate that the steroid hormone ecdysone coordinates both plasticity of organ size and robustness of organ pattern in the developing wings of the fruit fly Drosophila melanogaster. Using fed and starved larvae that lack prothoracic glands, which synthesise ecdysone, we show that nutrition regulates growth both via ecdysone and via an ecdysone-independent mechanism, while nutrition regulates patterning only via ecdysone. We then demonstrate that growth shows a graded response to ecdysone concentration, while patterning shows a threshold response. Collectively, these data support a model where nutritionally-regulated ecdysone fluctuations confer plasticity by regulating disc growth in response to basal ecdysone levels, and confers robustness by initiating patterning only once ecdysone peaks exceeds a threshold concentration. This could represent a generalizable mechanism through which hormones coordinate plastic growth with robust patterning in the face of environmental change.

developmental biology↗

bioRxiv2020

Maintaining robust size across environmental conditions is achieved through plastic growth dynamics in the central nervous system of Drosophila melanogaster

Organ growth is tightly regulated across environmental conditions to generate appropriate final size. While the size of some organs is free to vary, others need to maintain constant size to function properly. This poses a unique problem: how is robust final size achieved when environmental conditions can alter some major growth processes? While we know that brain growth is "spared" from the effects of the environment from humans to fruit flies, we do not understand how this process alters growth dynamics across brain compartments. Here, we explore how this robustness in brain size is achieved by examining differences in growth patterns between the larval body, the brain, and a brain compartment - the mushroom bodies - in Drosophila melanogaster across both thermal and nutritional conditions. We identify key differences in patterns of growth between the whole brain and mushroom bodies that are likely to underlie robustness of final organ shape. Further, we show that these differences produce distinct brain shapes across environments. Significance of StudyA long-standing question in Biology has been how fully functional multicellular organisms with highly specialized organs are generated, given that organs initiate growth at different times across development. Although the genetic mechanisms that underlie growth has been studied extensively, we are yet to understand how growth pattern of organs produces distinct final shapes across changing environmental conditions. We use the Drosophila brain, to reveal that key differences in growth dynamics are likely to underlie robustness of final organ shape and are tuned by nutrition and temperature. Further deepening our knowledge of how final organ shape is maintained across environmental conditions.

developmental biology↗

bioRxiv2020

Amino acid quality modifies the quantitative availability of protein for reproduction in Drosophila melanogaster

Diet composition, especially the relative abundance of key macronutrients, is well known to affect animal wellbeing by changing reproductive output, metabolism and length of life. However, less attention has been paid to the ways the quality of these nutrients modify these macronutrient interactions. Nutritional Geometry can be used to model the effects of multiple dietary components on life-history traits and to compare these responses when diet quality is varied. Previous studies have shown that dietary protein quality can be increased for egg production in Drosophila melanogaster by matching the dietary amino acid proportions to the balance of amino acids used by the sum of proteins in the flys in silico translated exome. Here, we show that dietary protein quality dramatically alters the effect of protein quantity on female reproduction across a broad range of diets varying in both protein and carbohydrate concentrations. These data show that when sources of ingredients vary, their relative value to the consumer can vastly differ and yield very different physiological outcomes. Such variations could be particularly important for meta analyses that look to draw generalisable conclusions from diverse studies.

physiology↗