Biology subjects

Kawecki, T. J.

Publications and source records attributed to Kawecki, T. J..

11 recordsLinked to original sources

bioRxiv2024

Methylparaben dampens virulence and transmissibility of the Drosophila pathogen Pseudomonas entomophila

In the last 20 years, Pseudomonas entomophila (Pe) has emerged as a model to explore insect immunity to bacterial intestinal pathogens. Laboratory studies evidenced multiple detrimental effects of Pe on Drosophila melanogaster. However, these effects require that the bacteria are ingested in extremely high concentrations of 1010 - 1011 CFU per mL (OD600 20 - 200), questioning the relevance of this pathogen in nature. Here, we tested whether the need for such high doses may be due to protective effects of the food preservative methylparaben (Nipagin), a standard ingredient of artificial Drosophila diets. While significant mortality in flies fed diet containing standard methylparaben concentration required doses of >1010 CFU per mL, when methylparaben was absent we could observe mortality using 500,000x lower doses. Consistent with these results, we demonstrated strong bactericidal properties of methylparaben on Pe in vitro. In the absence of methylparaben even the smallest inocula (105 CFU per mL) led to high bacterial loads (106 CFU per fly) after several days, indicating the ability of Pe to grow and overcome the flies defenses. We also demonstrate that in the absence of methylparaben, infected flies could easily transmit the pathogen to other adults and to offspring, resulting in high mortality and thus highlighting the potential of Pe as a pathogen of Drosophila in nature. Our study also underscores that careful consideration should be given to food additives used in standard diets in laboratory research on host-pathogen interaction. ImportanceAccurate characterization of pathogen infections requires appropriate experimental methodologies. Infections of insects with Pe are frequently studied using fruit flies as a model organism, with laboratory cultures typically maintained on artificial media containing various food preservatives. In this study, we show that one commonly used preservative, methylparaben, significantly influences the outcome of oral infections with Pe. We found that minimal infection doses, far below the standards of the field, could be still lethal to flies raised on media without methylparaben. This increased virulence was also associated with increased transmission of the pathogen, both from infected adult flies to their offspring and to uninfected adults. Our findings show how subtle variations in experimental conditions can profoundly affect how we perceive pathogenic threats.

immunology↗

bioRxiv2024

Evolutionary history with chronic malnutrition enhances pathogen susceptibility at older ages

Juvenile malnutrition is a global public health concern that negatively impacts the development and maturation of the immune system, leading to increased susceptibility to infectious diseases. Such adverse effects on immunity might increase with ageing, worsening disease conditions later in life. Furthermore, malnutrition may persist across generations, imposing strong natural selection to survive the nutrient shortage. However, it is unclear how the evolutionary history of ancestral generations with chronic malnutrition could influence pathogen resistance and infection susceptibility, as well as their age-specific changes in extant generations. To address this, we used Drosophila melanogaster populations adapted against chronic juvenile malnutrition and exposed them to a bacterial pathogen, Providencia rettgeri, during their early and late adulthood. Surprisingly, we observed that in populations adapted to chronic malnutrition, young flies survived infection better by tolerating the infection, while control flies displayed higher infection susceptibility despite carrying a similar pathogen load. However, this pattern in post-infection survival is reversed with ageing. There was no change in pathogen resistance, but evolved flies succumbed more to infection than control flies regardless of the input infection doses. Our study thus revealed new evolutionary insights into the development of contrasting early vs late-life immune strategies and age-specific vulnerabilities to infection as a function of early-life malnutrition.

evolutionary biology↗

bioRxiv2024

Context- and sex-dependent links between sire sexual success and offspring pathogen resistance

Sexual selection has been proposed to promote genetic variants that improve resistance to pathogens (a special case of the "good genes" hypothesis). Yet, experimental tests of this hypothesis are scarce and equivocal. It is often assumed that additive genetic correlation between sexual traits and pathogen resistance is generated by their shared dependence on genetically variable "condition" of the organism. However, an alternative scenario posits condition-independent genetic variation in pathogen resistance; individuals more resistant to currently prevalent pathogens remain healthier and can invest more in sexual traits, but this advantage disappears in the absence of pathogens. Here, we tested whether Drosophila melanogaster males that are more sexually competitive (in terms of paternity share) sire offspring that are more resistant to the fungal pathogen Metarhizium brunneum. Furthermore, to investigate the importance of epidemiological context, we exposed sires to either an infection or a sham treatment before mating, to test whether the sire-offspring relationship depends on the presence of pathogens during sexual selection. We found that the relationship between sires sexual success and offspring pathogen resistance not only depended on sires exposure to the pathogen, but also on offspring sex. Sires that were more sexually successful in the absence of the pathogen had less resistant offspring whereas no relationship was detected for sires that competed for paternity after pathogen exposure. For daughters, the relationship tended to be negative irrespective of sires pathogen exposure. In no case was a positive correlation predicted by the "good genes" hypothesis detected. Thus, while sexual selection may act on genes affecting resistance in a context- and sex-dependent manner, we found no circumstances under which it promoted resistance. Lay SummarySexual selection has been debated in relation to natural selection for decades. The "good genes" hypothesis which posits a positive genetic correlation between sexual success and non-sexual fitness, is often considered as a mechanism aligning sexual selection and natural selection. Scientists have long wondered if genetic variants that make individuals more sexually successful also enhance their ability to fight against pathogens, testing a special version of "good genes". However, evidence is mixed. Two key mechanisms linking sexual success and pathogen resistance have been proposed: the "condition- dependent" scenario, where general health improve both sexual traits and pathogen resistance, and the "context-dependent" scenario, where resistance to specific pathogens benefits sexual success only in certain environments. Few studies distinguish between these two mechanisms. This study examines both scenarios in Drosophila melanogaster, finding that the relationship between a sires mating success and offspring pathogen resistance to the fungal pathogen Metarhizium brunneum depends on sires pathogen exposure prior to measurement of sexual success and offspring sex. These findings challenge the "good genes" hypothesis and emphasize the necessity of including context in sexual selection studies.

evolutionary biology↗

bioRxiv2024

Shared genetic architecture links energy metabolism, behavior and starvation resistance along a power-endurance axis

Shared developmental, physiological and molecular mechanisms can generate strong genetic covariances across suites of traits, constraining genetic variability and evolvability to certain axes in multivariate trait space ("variational modules" or "syndromes"). Such trait suites will not only respond jointly to selection; they will also covary across populations that diverged from one another by genetic drift. We report evidence for such a genetically correlated trait suite in Drosophila melanogaster. It links high expression of glycolysis and TCA cycle genes, high abundance of mitochondria and high spontaneous locomotor activity with low degree of adiposity, and low endurance and early death under starvation. This "power-endurance" axis is also aligned with abundance of certain metabolites, notably low trehalose (blood sugar) and high levels of some amino acids and their derivatives, including creatine, a compound known to facilitate energy production in muscles. Our evidence comes from six replicate "Selected" populations adapted to a nutrient-poor larval diet regime during 250 generations of experimental evolution and six "Control" populations evolved in parallel on a standard diet regime. We found that, within each of these experimental evolutionary regime, the above traits strongly covaried along the power-endurance axis across replicate populations which diversified by drift, indicating a shared genetic architecture. The two evolutionary regimes also drove divergence along this axis, with Selected populations on average displaced towards the "power" direction compared to Controls. Aspects of this "power-endurance" axis resemble the "pace of life" syndrome and the "thrifty phenotype"; it may have evolved as part of a coordinated organismal response to nutritional conditions.

evolutionary biology↗

bioRxiv2023

Cis-regulatory polymorphism at fiz ecdysone oxidase contributes to polygenic adaptation to malnutrition in Drosophila

We investigate the contribution of a candidate gene, fiz (fezzik), to complex polygenic adaptation to juvenile malnutrition in Drosophila melanogaster. We show that experimental populations adapted during >250 generations of experimental evolution to a nutritionally poor larval diet (Selected populations) evolved several-fold lower fiz expression compared to unselected Control populations. This divergence in fiz expression is mediated by a cis-regulatory polymorphism. This polymorphism, which was originally present in a sample from a natural population in Switzerland, is distinct from a second cis-regulatory SNP previously identified in non-African D. melanogaster populations, implying that two independent cis-regulatory variants promoting high fiz expression segregate in non-African populations. Enzymatic analyses of Fiz protein expressed in E. coli demonstrate that it has ecdysone oxidase activity acting on both ecdysone and 20-hydroxyecdysone. Four of five fiz paralogs annotated to ecdysteroid metabolism also show reduced expression in Selected larvae, suggesting that malnutrition-driven selection favored general downregulation of ecdysone oxidases. Finally, as an independent test of the role of fiz in poor diet adaptation, we show that fiz knockdown by RNAi results in faster larval growth on the poor diet, but at the cost of greatly reduced survival. These results imply that downregulation of fiz in Selected populations was favored because of its role in suppressing growth in response to nutrient shortage. However, fiz downregulation is only adaptive in combination with other changes evolved by Selected populations, such as in nutrient acquisition and metabolism, which ensure that the organism can actually sustain the faster growth promoted by fiz downregulation.

evolutionary biology↗

bioRxiv2023

Experimental evolution of metabolism under nutrient restriction: enhanced amino acid catabolism and a key role of branched-chain amino acids

Periodic food shortage is a common ecological stressor for animals, likely to drive physiological and metabolic adaptations to alleviate its consequences, particularly for juveniles that have no option but to continue to grow and develop despite undernutrition. Here we study changes in metabolism associated with adaptation to nutrient shortage, evolved by replicate Drosophila melanogaster populations maintained on a nutrient-poor larval diet for over 240 generations. In a factorial metabolomics experiment we showed that both phenotypic plasticity and genetically-based adaptation to the poor diet involved wide-ranging changes in metabolite abundance; however, the plastic response did not predict the evolutionary change. Compared to non-adapted larvae exposed to the poor diet for the first time, the adapted larvae showed lower levels of multiple free amino acids in their tissues - and yet they grew faster. By quantifying accumulation of the nitrogen stable isotope 15N we show that adaptation to the poor diet led to an increased use of amino acids for energy generation. This apparent "waste" of scarce amino acids likely results from the trade-off between acquisition of dietary amino acids and carbohydrates observed in these populations. The three branched-chain amino acids (leucine, isoleucine and valine) showed a unique pattern of depletion in adapted larvae raised on the poor diet. A diet supplementation experiment demonstrated that these amino acids are limiting for growth on the poor diet, suggesting that their low levels resulted from their expeditious use for protein synthesis. These results demonstrate that selection driven by nutrient shortage not only promotes improved acquisition of limiting nutrients, but also has wide-ranging effects on how the nutrients are used. They also show that the abundance of free amino acids in the tissues does not, in general, reflect the nutritional condition and growth potential of an animal. Lay summaryJuvenile animals are particularly vulnerable to nutrient deprivation - they usually do not have an option of arresting their development and just trying to survive until food becomes plentiful; rather, they must attempt to grow and develop with whatever nutrients that can scrape. While they could obviously improve their lot by getting better at finding the scarce food, could they also adapt their physiology and metabolism in a way that would alleviate consequences of undernutrition? To find out we let populations of the fruit fly Drosophila melanogaster adapt during 240 generations to conditions of chronic larval nutrient shortage, and then studied their metabolism. We found that these populations evolved changes in their amino acid metabolism: their larvae are better at extracting amino acids from nutritionally poor diet and are able to grow faster (which requires a higher rate of protein synthesis), while maintaining lower levels of most amino acids in their system. This suggests improved cellular "logistics", with a higher turnover of raw materials associated with their lower stocks owing to their more efficient and immediate use. However, paradoxically, the malnutrition-adapted larvae also "waste" a substantial fraction of their amino acids by "burning" them for energy. They can afford this because of their improved extraction of scarce amino acid from the diet, but they may also be compelled to do this by a trade-off with absorption of dietary carbohydrates.

evolutionary biology↗

bioRxiv2023

An Ancestral Balanced Inversion Polymorphism Confers Global Adaptation

Since the pioneering work of Dobzhansky in the 1930s and 1940s, many chromosomal inversions have been identified but how they contribute to adaptation remains poorly understood. In Drosophila melanogaster, the widespread inversion polymorphism In(3R)Payne underpins latitudinal clines in fitness traits on multiple continents. Here, we use single-individual whole-genome sequencing, transcriptomics and published sequencing data to study the population genomics of this inversion on four continents: in its ancestral African range and in derived populations in Europe, North America, and Australia. Our results confirm that this inversion originated in sub-Saharan Africa and subsequently became cosmopolitan; we observe marked monophyletic divergence of inverted and non-inverted karyotypes, with some substructure among inverted chromosomes between continents. Despite divergent evolution of this inversion since its out-of-Africa migration, derived non-African populations exhibit similar patterns of long-range linkage disequilibrium between the inversion breakpoints and major peaks of divergence in its center, consistent with balancing selection and suggesting that the inversion harbors alleles that are maintained by selection on several continents. Using RNA-seq we identify overlap between inversion-linked SNPs and loci that are differentially expressed between inverted and non-inverted chromosomes. Expression levels are higher for inverted chromosomes at low temperature, suggesting loss of buffering or compensatory plasticity and consistent with higher inversion frequency in warm climates. Our results suggest that this ancestrally tropical balanced polymorphism spread around the world and became latitudinally assorted along similar but independent climatic gradients, always being frequent in subtropical/tropical areas but rare or absent in temperate climates.

evolutionary biology↗

bioRxiv2022

Evolution under juvenile malnutrition impacts adult metabolism and fitness

Juvenile undernutrition has lasting effects on adult metabolism of the affected individuals, but it is unclear how adult physiology is shaped over evolutionary time by natural selection driven by juvenile undernutrition. We combined RNAseq, targeted metabolomics and genomics to study the consequences of evolution under juvenile undernutrition for metabolism of reproductively active adult females of Drosophila melanogaster. Compared to Control populations maintained on standard diet, Selected populations maintained for over 230 generations on a nutrient-poor larval diet evolved major changes in adult gene expression and metabolite abundance, in particular affecting amino-acid and purine metabolism. The evolved differences in adult gene expression and metabolite abundance between Selected and Control populations were positively correlated with the corresponding differences previously reported for Selected versus Control larvae. This implies that genetic variants affect both stages similarly. Even when well fed, the metabolic profile of Selected flies resembled that of flies subject to starvation. Finally, Selected flies had lower reproductive output than Controls even when both were raised under the conditions under which the Selected populations evolved. These results imply that evolutionary adaptation to juvenile undernutrition has large pleiotropic consequences for adult metabolism, and that they are costly rather than adaptive for adult fitness. Thus, juvenile and adult metabolism do not appear to evolve independently from each other even in a holometabolous species where the two life stages are separated by a complete metamorphosis.

evolutionary biology↗

bioRxiv2020

The genomic architecture of adaptation to larval malnutrition points to a trade-off with adult starvation resistance in Drosophila

Periods of nutrient shortage impose strong selection on animal populations. Experimental studies of genetic adaptation to nutrient shortage largely focus on resistance to acute starvation at adult stage; it is not clear how conclusions drawn from these studies extrapolate to other forms of nutritional stress. We studied the genomic signature of adaptation to chronic juvenile malnutrition in six populations of Drosophila melanogaster evolved for 150 generations on an extremely nutrient-poor larval diet. Comparison with control populations evolved on standard food revealed repeatable genomic differentiation between the two set of population, involving >3,000 candidate SNPs forming >100 independently evolving clusters. The candidate genomic regions were enriched in genes implicated in hormone, carbohydrate, and lipid metabolism, including some with known effects on fitness-related life-history traits. Rather than being close to fixation, a substantial fraction of candidate SNPs segregated at intermediate allele frequencies in all malnutrition-adapted populations. This, together with patterns of among-population variation in allele frequencies and estimates of Tajimas D, suggests that the poor diet results in balancing selection on some genomic regions. Our candidate genes for tolerance to larval malnutrition showed a high overlap with genes previously implicated in acute starvation resistance. However, adaptation to larval malnutrition in our study was associated with reduced tolerance to acute adult starvation. Thus, rather than reflecting synergy, the shared genomic architecture appears to mediate an evolutionary trade-off between tolerances to these two forms of nutritional stress.

evolutionary biology↗

bioRxiv2018

Natural variation in couch potato mediates rapid evolution of learning and reproduction in natural populations of Drosophila melanogaster

Learning is a general mechanism of adaptive behavioural plasticity whose benefits and costs depend on the environment. Thus, seasonal oscillations in temperate environments between winter and summer might produce cyclical selection pressures that would drive rapid evolution of learning performance in multivoltine populations. To test this hypothesis, we investigated the evolutionary dynamics of learning ability over this rapid seasonal timescale in a natural population of Drosophila melanogaster. Associative learning was tested in common garden-raised flies collected from nature in the spring and fall over three consecutive years. The spring flies consistently learned better than fall flies, revealing seasonal evolution of improved learning performance in nature. Fecundity showed the opposite seasonal pattern, suggesting a trade-off between learning and reproduction. This trade-off also held within population: more fecund individual females learned less well. This trade-off is mediated at least in part by natural polymorphism in the RNA binding protein couch potato (cpo), with a genotype favoured during summer showing poorer learning performance and higher fecundity than a genotype favoured over winter. Thus, seasonal environments can drive rapid cyclical evolution of learning performance, but the evolutionary dynamics may be driven by trade-offs generated by pleiotropic effects of causative alleles selected for other reasons.

evolutionary biology↗

bioRxiv2017

Adaptation to chronic malnutrition leads to reduced dependence on microbiota in Drosophila

Numerous studies have shown that animal nutrition is tightly linked to gut microbiota, especially under nutritional stress. In Drosophila, microbiota are known to promote juvenile growth, development and survival on poor diets, mainly through enhanced digestion leading to changes in hormonal signaling. Here we show that this reliance on microbiota is greatly reduced in replicated Drosophila populations that adapted to a poor larval diet in the course of over 170 generations of experimental evolution. Protein and polysaccharide digestion in these malnutrition-adapted populations became much less dependent on colonization with microbiota. This was accompanied by changes in at least some targets of dFOXO transcription factor, which is a key regulator of cell growth and survival. Our study suggests that some metazoans have retained the evolutionary potential to adapt their physiology such that association with microbiota may become optional rather than essential.

evolutionary biology↗