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Among the many wonders of nature, the sense of smell of the fly Drosophila melanogaster might seem, at first glance, of esoteric interest. Nevertheless, for over a century, the 'nose' of this insect has been an extraordinary system to explore questions in animal behaviour, ecology and evolution, neuroscience, physiology and molecular genetics. The insights gained are relevant for our understanding of the sensory biology of vertebrates, including humans, and other insect species, encompassing those detrimental to human health. Here, I present an overview of our current knowledge of D. melanogaster olfaction, from molecules to behaviours, with an emphasis on the historical motivations of studies and illustration of how technical innovations have enabled advances. I also highlight some of the pressing and long-term questions.

The methyl cycle is a universal metabolic pathway providing methyl groups for the methylation of nuclei acids and proteins, regulating all aspects of cellular physiology. We have previously shown that methyl cycle inhibition in mammals strongly affects circadian rhythms. Since the methyl cycle and circadian clocks have evolved early during evolution and operate in organisms across the tree of life, we sought to determine whether the link between the two is also conserved. Here, we show that methyl cycle inhibition affects biological rhythms in species ranging from unicellular algae to humans, separated by more than 1 billion years of evolution. In contrast, the cyanobacterial clock is resistant to methyl cycle inhibition, although we demonstrate that methylations themselves regulate circadian rhythms in this organism. Mammalian cells with a rewired bacteria-like methyl cycle are protected, like cyanobacteria, from methyl cycle inhibition, providing interesting new possibilities for the treatment of methylation deficiencies., Fustin et al. reveal the evolutionarily conserved link between methyl metabolism and biological clocks. This study suggests the possibility of translating fundamental understanding of methylation deficiencies to clinical applications.

A fundamental aim of adaptation genomics is to identify polymorphisms that underpin variation in fitness traits. InD. melanogasterlatitudinal life-history clines exist on multiple continents and make an excellent system for dissecting the genetics of adaptation. We have previously identified numerous clinal SNPs in insulin/insulin-like growth factor signaling (IIS), a pathway known from mutant studies to affect life history. However, the effects of natural variants in this pathway remain poorly understood. Here we investigate how two clinal alternative alleles atfoxo, a transcriptional effector of IIS, affect fitness components (viability, size, starvation resistance, fat content). We assessed this polymorphism from the North American cline by reconstituting outbred populations, fixed for either the low- or high-latitude allele, from inbred DGRP lines. Since diet and temperature modulate IIS, we phenotyped alleles across two temperatures (18°C, 25°C) and two diets differing in sugar source and content. Consistent with clinal expectations, the high-latitude allele conferred larger body size and reduced wing loading. Alleles also differed in starvation resistance and expression ofInR, a transcriptional target of FOXO. Allelic reaction norms were mostly parallel, with few GxE interactions. Together, our results suggest that variation in IIS makes a major contribution to clinal life-history adaptation.

Resistance to pathogens is often invoked as an indirect benefit of female choice, but experimental evidence for links between father's sexual success and offspring resistance is scarce and equivocal. Two proposed mechanisms might generate such links. Under the first, heritable resistance to diverse pathogens depends on general immunocompetence; owing to shared condition dependence, male sexual traits indicate immunocompetence independently of the male's pathogen exposure. By contrast, other hypotheses (e.g. Hamilton–Zuk) assume that sexual traits only reveal heritable resistance if the males have been exposed to the pathogen. The distinction between the two mechanisms has been neglected by experimental studies. We show that Drosophila melanogaster males that are successful in mating contests (one female with two males) sire sons that are substantially more resistant to the intestinal pathogen Pseudomonas entomophila —but only if the males have themselves been exposed to the pathogen before the mating contest. By contrast, sons of males sexually successful in the absence of pathogen exposure are less resistant than sons of unsuccessful males. We detected no differences in daughters’ resistance. Thus, while sexual selection may have considerable consequences for offspring resistance, these consequences may be sex-specific. Furthermore, contrary to the ‘general immunocompetence’ hypothesis, these consequences can be positive or negative depending on the epidemiological context under which sexual selection operates.

In many animals, females respond to mating with changes in physiology and behavior that are triggered by molecules transferred by males during mating. In Drosophila melanogaster, proteins in the seminal fluid are responsible for important female postmating responses, including temporal changes in egg production, elevated feeding rates and activity levels, reduced sexual receptivity, and activation of the immune system. It is unclear to what extent these changes are mutually beneficial to females and males or instead represent male manipulation. Here we use an experimental evolution approach in which females are randomly paired with a single male each generation, eliminating any opportunity for competition for mates or mate choice and thereby aligning the evolutionary interests of the sexes. After >150 generations of evolution, males from monogamous populations elicited a weaker postmating stimulation of egg production and activity than males from control populations that evolved with a polygamous mating system. Males from monogamous populations did not differ from males from polygamous populations in their ability to induce refractoriness to remating in females, but they were inferior to polygamous males in sperm competition. Mating-responsive genes in both the female abdomen and head showed a dampened response to mating with males from monogamous populations. Males from monogamous populations also exhibited lower expression of genes encoding seminal fluid proteins, which mediate the female response to mating. Together, these results demonstrate that the female postmating response, and the male molecules involved in eliciting this response, are shaped by ongoing sexual conflict.

Metazoans viability depends on their ability to regulate metabolic processes and also to respond to harmful challenges by mounting anti‐stress responses; these adaptations were fundamental forces during evolution. Central to anti‐stress responses are a number of short‐lived transcription factors that by functioning as stress sensors mobilize genomic responses aiming to eliminate stressors. We show here that increased expression of nuclear factor erythroid 2‐related factor (Nrf2) in Drosophila activated cytoprotective modules and enhanced stress tolerance. However, while mild Nrf2 activation extended lifespan, high Nrf2 expression levels resulted in developmental lethality or, after inducible activation in adult flies, in altered mitochondrial bioenergetics, the appearance of Diabetes Type 1 hallmarks and aging acceleration. Genetic or dietary suppression of Insulin/IGF‐like signaling (IIS) titrated Nrf2 activity to lower levels, largely normalized metabolic pathways signaling, and extended flies’ lifespan. Thus, prolonged stress signaling by otherwise cytoprotective short‐lived stress sensors perturbs IIS resulting in re‐allocation of resources from growth and longevity to somatic preservation and stress tolerance. These findings provide a reasonable explanation of why most (if not all) cytoprotective stress sensors are short‐lived proteins, and it also explains the build‐in negative feedback loops (shown here for Nrf2); the low basal levels of these proteins, and why their suppressors were favored by evolution.

Experimental evolution (EE) is a powerful tool for addressing how environmental factors influence life-history evolution. While in nature different selection pressures experienced across the lifespan shape life histories, EE studies typically apply selection pressures one at a time. Here we assess the consequences of adaptation to three different developmental diets in combination with classical selection for early or late reproduction in the fruit fly Drosophila melanogaster. We find that the response to each selection pressure is similar to that observed when they are applied independently, but the overall magnitude of the response depends on the selection regime experienced in the other life stage. For example, adaptation to increased age at reproduction increased lifespan across all diets, however, the extent of the increase was dependent on the dietary selection regime. Similarly, adaptation to a lower calorie developmental diet led to faster development and decreased adult weight, but the magnitude of the response was dependent on the age-at-reproduction selection regime. Given that multiple selection pressures are prevalent in nature, our findings suggest that trade-offs should be considered not only among traits within an organism, but also among adaptive responses to different - sometimes conflicting - selection pressures, including across life stages.

Numerous studies have shown that animal nutrition is tightly linked to gut microbiota, especially under nutritional stress. In Drosophila melanogaster , 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 became genetically adapted to a poor larval diet in the course of over 170 generations of experimental evolution. Protein and polysaccharide digestion in these poor-diet-adapted populations became much less dependent on colonization with microbiota. This was accompanied by changes in expression levels of dFOXO transcription factor, a key regulator of cell growth and survival, and many of its targets. These evolutionary changes in the expression of dFOXO targets to a large degree mimic the response of the same genes to microbiota, suggesting that the evolutionary adaptation to poor diet acted on mechanisms that normally mediate the response to microbiota. 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. IMPORTANCE Animals depend on gut microbiota for various metabolic tasks, particularly under conditions of nutritional stress, a relationship usually regarded as an inherent aspect of animal physiology. Here, we use experimental evolution in fly populations to show that the degree of host dependence on microbiota can substantially and rapidly change as the host population evolves in response to poor diet. Our results suggest that, although microbiota may initially greatly facilitate coping with suboptimal diets, chronic nutritional stress experienced over multiple generations leads to evolutionary adaptation in physiology and gut digestive properties that reduces dependence on the microbiota for growth and survival. Thus, despite its ancient evolutionary history, the reliance of animal hosts on their microbial partners can be surprisingly flexible and may be relaxed by short-term evolution.

To escape danger or catch prey, running vertebrates rely on dynamic gaits with minimal ground contact. By contrast, most insects use a tripod gait that maintains at least three legs on the ground at any given time. One prevailing hypothesis for this difference in fast locomotor strategies is that tripod locomotion allows insects to rapidly navigate three-dimensional terrain. To test this, we computationally discovered fast locomotor gaits for a model based on Drosophila melanogaster. Indeed, the tripod gait emerges to the exclusion of many other possible gaits when optimizing fast upward climbing with leg adhesion. By contrast, novel two-legged bipod gaits are fastest on flat terrain without adhesion in the model and in a hexapod robot. Intriguingly, when adhesive leg structures in real Drosophila are covered, animals exhibit atypical bipod-like leg coordination. We propose that the requirement to climb vertical terrain may drive the prevalence of the tripod gait over faster alternative gaits with minimal ground contact., Numerous selective forces shape animal locomotion patterns and as a result, different animals evolved to use different gaits. Here, Ramdya et al. use live and in silico Drosophila, as well as an insect-model robot, to gain insights into the conditions that promote the ubiquitous tripod gait observed in most insects.

Textural properties provide information on the ingestibility, digestibility and state of ripeness or decay of sources of nutrition. Compared with our understanding of the chemosensory assessment of food, little is known about the mechanisms of texture detection. Here we show that Drosophila melanogaster can discriminate food texture, avoiding substrates that are either too hard or too soft. Manipulations of food substrate properties and flies' chemosensory inputs indicate that texture preferences are revealed only in the presence of an appetitive stimulus, but are not because of changes in nutrient accessibility, suggesting that animals discriminate the substrates' mechanical characteristics. We show that texture preference requires NOMPC, a TRP-family mechanosensory channel. NOMPC localizes to the sensory dendrites of neurons housed within gustatory sensilla, and is essential for their mechanosensory-evoked responses. Our results identify a sensory pathway for texture detection and reveal the behavioural integration of chemical and physical qualities of food., The cellular and molecular mechanisms underlying food texture detection are poorly understood. Here the authors show that Drosophila can discriminate food texture when feeding, and that this ability depends on NOMPC, a mechanosensory channel expressed in gustatory sensilla neurons.

26 p.-1 fig.-1 tab. Galluzzi, Lorenzo et al., Over the past two decades, the molecular machinery that underlies autophagic responses has been characterized with ever increasing precision in multiple model organisms. Moreover, it has become clear that autophagy and autophagy-related processes have profound implications for human pathophysiology. However, considerable confusion persists about the use of appropriate terms to indicate specific types of autophagy and some components of the autophagy machinery, which may have detrimental effects on the expansion of the field. Driven by the overt recognition of such a potential obstacle, a panel of leading experts in the field attempts here to define several autophagy-related terms based on specific biochemical features. The ultimate objective of this collaborative exchange is to formulate recommendations that facilitate the dissemination of knowledge within and outside the field of autophagy research.

The neural mechanisms determining the timing of even simple actions, such as when to walk or rest, are largely mysterious. One intriguing, but untested, hypothesis posits a role for ongoing activity fluctuations in neurons of central action selection circuits that drive animal behavior from moment to moment. To examine how fluctuating activity can contribute to action timing, we paired high-resolution measurements of freely walking Drosophila melanogaster with data-driven neural network modeling and dynamical systems analysis. We generated fluctuation-driven network models whose outputs—locomotor bouts—matched those measured from sensory-deprived Drosophila. From these models, we identified those that could also reproduce a second, unrelated dataset: the complex time-course of odor-evoked walking for genetically diverse Drosophila strains. Dynamical models that best reproduced both Drosophila basal and odor-evoked locomotor patterns exhibited specific characteristics. First, ongoing fluctuations were required. In a stochastic resonance-like manner, these fluctuations allowed neural activity to escape stable equilibria and to exceed a threshold for locomotion. Second, odor-induced shifts of equilibria in these models caused a depression in locomotor frequency following olfactory stimulation. Our models predict that activity fluctuations in action selection circuits cause behavioral output to more closely match sensory drive and may therefore enhance navigation in complex sensory environments. Together these data reveal how simple neural dynamics, when coupled with activity fluctuations, can give rise to complex patterns of animal behavior., Author Summary The brain is never quiet. Even in the absence of environmental cues, neurons receive and produce an ongoing barrage of fluctuating signals. These fluctuations are well studied in the sensory periphery but their potential influence on central circuits and behavior are unknown. In particular, activity fluctuations in action selection circuits—neural populations that drive an animal’s actions from moment to moment—may strongly influence behavior. To shed light on the influence of activity fluctuations on action timing, we developed a computational approach for automatically generating neural network models that reproduce large-scale, high-resolution behavioral measurements of freely walking Drosophila melanogaster. We found that models require stochastic activity fluctuations to reproduce complex Drosophila locomotor patterns. Specific fluctuation-driven dynamics allow these models to produce short and long bouts of locomotion in the absence of sensory cues and to reduce locomotor activity after sensory stimulation. These results support a role for ongoing activity fluctuations in the timing of animal behavior and reveal how behavioral shifts can be brought about through changes in the dynamics of neural circuits. Thus, simple dynamical mechanisms may underlie complex patterns of animal behavior.

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and health span. However, few fruits are known to improve the survival and health span in animals, let alone the underlying mechanisms. Here we investigate the effects of nectarine, a globally consumed fruit, on life span and health span in Drosophila melanogaster. Wild-type flies were fed standard, dietary restriction (DR), or high-fat diet supplemented with 0-4% nectarine extract. We measured life span, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-hydroxynonenal-protein adduct in these flies. We also measured life span, locomotor activity, and oxidative damage in sod1 mutant flies on the standard diet supplemented with 0-4% nectarine. Supplementation with 4% nectarine extended life span, increased fecundity, and decreased expression of some metabolic genes, including a key gluconeogenesis gene, PEPCK, and oxidative stress-response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR, or high-fat diet. Nectarine reduced oxidative damage in wild-type females fed the high-fat diet. Moreover, nectarine improved the survival of and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and health span partly by modulating glucose metabolism and reducing oxidative damage.

International audience; How do evolved genetic changes alter the nervous system to produce different patterns of behavior? We address this question using Drosophila male courtship behavior, which is innate, stereotyped, and evolves rapidly between species. D. melanogaster male courtship requires the male-specific isoforms of two transcription factors, fruitless and doublesex. These genes underlie genetic switches between female and male behaviors, making them excellent candidate genes for courtship behavior evolution. We tested their role in courtship evolution by transferring the entire locus for each gene from divergent species to D. melanogaster. We found that despite differences in Fru+ and Dsx+ cell numbers in wild-type species, cross-species transgenes rescued D. melanogaster courtship behavior and no species-specific behaviors were conferred. Therefore, fru and dsx are not a significant source of evolutionary variation in courtship behavior.