Male manipulation impinges on social-dependent tumor suppression in Drosophila melanogaster females.

Physiological status can influence social behavior, which in turn can affect physiology and health. Previously, we reported that tumor growth in Drosophila virgin females depends on the social context, but did not investigate the underlying physiological mechanisms. Here, we sought to characterize the signal perceived between tumorous flies, ultimately discovering that the tumor suppressive effect varies depending on reproductive status. Firstly, we show that the tumor suppressive effect is neither dependent on remnant pheromone-like products nor on the microbiota. Transcriptome analysis of the heads of these tumorous flies reveals social-dependent gene-expression changes related to nervous-system activity, suggesting that a cognitive-like relay might mediate the tumor suppressive effect. The transcriptome also reveals changes in the expression of genes related to mating behavior. Surprisingly, we observed that this social-dependent tumor-suppressive effect is lost in fertilized females. After mating, Drosophila females change their behavior-favoring offspring survival-in response to peptides transferred via the male ejaculate, a phenomenon called "male manipulation". Remarkably, the social-dependent tumor suppressive effect is restored in females mated by sex-peptide deficient males. Since male manipulation has likely been selected to favor male gene transmission, our findings indicate that this evolutionary trait impedes social-dependent tumor growth slowdown.

Social environment mediates cancer progression in Drosophila.

The influence of oncogenic phenomena on the ecology and evolution of animal species is becoming an important research topic. Similar to host-pathogen interactions, cancer negatively affects host fitness, which should lead to the selection of host control mechanisms, including behavioral traits that best minimize the proliferation of malignant cells. Social behavior is suggested to influence tumor progression. While the ecological benefits of sociality in gregarious species are widely acknowledged, only limited data are available on the role of the social environment on cancer progression. Here, we exposed adult Drosophila, with colorectal-like tumors, to different social environments. We show how subtle variations in social structure have dramatic effects on the progression of tumor growth. Finally, we reveal that flies can discriminate between individuals at different stages of tumor development and selectively choose their social environment accordingly. Our study demonstrates the reciprocal links between cancer and social interactions and how sociality may impact health and fitness in animals and its potential implications for disease ecology.

Changes in diet associated with cancer: An evolutionary perspective.

Changes in diet are frequently correlated with the occurrence and progression of malignant tumors (i.e., cancer) in both humans and other animals, but an integrated conceptual framework to interpret these changes still needs to be developed. Our aim is to provide a new perspective on dietary changes in tumor-bearing individuals by adapting concepts from parasitology. Dietary changes may occur alongside tumor progression for several reasons: (i) as a pathological side effect with no adaptive value, (ii) as the result of self-medication by the host to eradicate the tumor and/or to slow down its progression, (iii) as a result of host manipulation by the tumor that benefits its progression, and finally (iv) as a host tolerance strategy, to alleviate and repair damages caused by tumor progression. Surprisingly, this tolerance strategy can be beneficial for the host even if diet changes are beneficial to tumor progression, provided that cancer-induced death occurs sufficiently late (i.e., when natural selection is weak). We argue that more data and a unifying evolutionary framework, especially during the early stages of tumorigenesis, are needed to understand the links between changes in diet and tumor progression. We argue that a focus on dietary changes accompanying tumor progression can offer novel preventive and therapeutic strategies against cancer.

Cancer brings forward oviposition in the fly Drosophila melanogaster.

Hosts often accelerate their reproductive effort in response to a parasitic infection, especially when their chances of future reproduction decrease with time from the onset of the infection. Because malignancies usually reduce survival, and hence potentially the fitness, it is expected that hosts with early cancer could have evolved to adjust their life-history traits to maximize their immediate reproductive effort. Despite the potential importance of these plastic responses, little attention has been devoted to explore how cancers influence animal reproduction. Here, we use an experimental setup, a colony of genetically modified flies Drosophila melanogaster which develop colorectal cancer in the anterior gut, to show the role of cancer in altering life-history traits. Specifically, we tested whether females adapt their reproductive strategy in response to harboring cancer. We found that flies with cancer reached the peak period of oviposition significantly earlier (i.e., 2 days) than healthy ones, while no difference in the length and extent of the fecundity peak was observed between the two groups of flies. Such compensatory responses to overcome the fitness-limiting effect of cancer could explain the persistence of inherited cancer-causing mutant alleles in the wild.

Understanding Dynamics of Information Transmission in Drosophila melanogaster Using a Statistical Modeling Framework for Longitudinal Network Data (the RSiena Package).

Social learning - the transmission of behaviors through observation or interaction with conspecifics - can be viewed as a decision-making process driven by interactions among individuals. Animal group structures change over time and interactions among individuals occur in particular orders that may be repeated following specific patterns, change in their nature, or disappear completely. Here we used a stochastic actor-oriented model built using the RSiena package in R to estimate individual behaviors and their changes through time, by analyzing the dynamic of the interaction network of the fruit fly Drosophila melanogaster during social learning experiments. In particular, we re-analyzed an experimental dataset where uninformed flies, left free to interact with informed ones, acquired and later used information about oviposition site choice obtained by social interactions. We estimated the degree to which the uninformed flies had successfully acquired the information carried by informed individuals using the proportion of eggs laid by uninformed flies on the medium their conspecifics had been trained to favor. Regardless of the degree of information acquisition measured in uninformed individuals, they always received and started interactions more frequently than informed ones did. However, information was efficiently transmitted (i.e., uninformed flies predominantly laid eggs on the same medium informed ones had learn to prefer) only when the difference in contacts sent between the two fly types was small. Interestingly, we found that the degree of reciprocation, the tendency of individuals to form mutual connections between each other, strongly affected oviposition site choice in uninformed flies. This work highlights the great potential of RSiena and its utility in the studies of interaction networks among non-human animals.

Fighting experience affects fruit fly behavior in a mating context.

In animals, correlations exist among behaviors within individuals, but it is unclear whether experience in a specific functional context can affect behavior across different contexts. Here, we use Drosophila melanogaster to investigate the effects of conflict-induced behavioral modifications on male mating behavior. In D. melanogaster, males fight for territories and experience a strong winner-loser effect, meaning that winners become more likely to win subsequent fights compared to losers, who continue to lose. In our protocol, males were tested for courtship intensity before and after fighting against other males. We show that male motivation to copulate before fights cannot predict the fight outcomes, but that, afterwards, losers mate less than before and less than winner and control males. Contrarily, winners show no differences between pre- and post-fight courtship intensity, and do not differ from control males. This suggests that the physiological modifications resulting from fight outcomes indirectly affect male reproductive behavior.

Introduced Drosophila subobscura populations perform better than native populations during an oviposition choice task due to increased fecundity but similar learning ability.

The success of invasive species is tightly linked to their fitness in a putatively novel environment. While quantitative components of fitness have been studied extensively in the context of invasive species, fewer studies have looked at qualitative components of fitness, such as behavioral plasticity, and their interaction with quantitative components, despite intuitive benefits over the course of an invasion. In particular, learning is a form of behavioral plasticity that makes it possible to finely tune behavior according to environmental conditions. Learning can be crucial for survival and reproduction of introduced organisms in novel areas, for example, for detecting new predators, or finding mates or oviposition sites. Here we explored how oviposition performance evolved in relation to both fecundity and learning during an invasion, using native and introduced Drosophila subobscura populations performing an ecologically relevant task. Our results indicated that, under comparable conditions, invasive populations performed better during our oviposition task than did native populations. This was because invasive populations had higher fecundity, together with similar cognitive performance when compared to native populations, and that there was no interaction between learning and fecundity. Unexpectedly, our study did not reveal an allocation trade-off (i.e., a negative relationship) between learning and fecundity. On the contrary, the pattern we observed was more consistent with an acquisition trade-off, meaning that fecundity could be limited by availability of resources, unlike cognitive ability. This pattern might be the consequence of escaping natural enemies and/or competitors during the introduction. The apparent lack of evolution of learning may indicate that the introduced population did not face novel cognitive challenges in the new environment (i.e., cognitive "pre-adaptation"). Alternatively, the evolution of learning may have been transient and therefore not detected.

How social network structure affects decision-making in Drosophila melanogaster.

Animals use a number of different mechanisms to acquire crucial information. During social encounters, animals can pass information from one to another but, ideally, they would only use information that benefits survival and reproduction. Therefore, individuals need to be able to determine the value of the information they receive. One cue can come from the behaviour of other individuals that are already using the information. Using a previous extended dataset, we studied how individual decision-making is influenced by the behaviour of conspecifics in Drosophila melanogaster. We analysed how uninformed flies acquire and later use information about oviposition site choice they learn from informed flies. Our results suggest that uninformed flies adjust their future choices based on how coordinated the behaviours of the informed individuals they encounter are. Following social interaction, uninformed flies tended either to collectively follow the choice of the informed flies or to avoid it. Using social network analysis, we show that this selective information use seems to be based on the level of homogeneity of the social network. In particular, we found that the variance of individual centrality parameters among informed flies was lower in the case of a 'follow' outcome compared with the case of an 'avoid' outcome.

Genetic variation in aggregation behaviour and interacting phenotypes in Drosophila.

Aggregation behaviour is the tendency for animals to group together, which may have important consequences on individual fitness. We used a combination of experimental and simulation approaches to study how genetic variation and social environment interact to influence aggregation dynamics in Drosophila To do this, we used two different natural lines of Drosophila that arise from a polymorphism in the foraging gene (rovers and sitters). We placed groups of flies in a heated arena. Flies could freely move towards one of two small, cooler refuge areas. In groups of the same strain, sitters had a greater tendency to aggregate. The observed behavioural variation was based on only two parameters: the probability of entering a refuge and the likelihood of choosing a refuge based on the number of individuals present. We then directly addressed how different strains interact by mixing rovers and sitters within a group. Aggregation behaviour of each line was strongly affected by the presence of the other strain, without changing the decision rules used by each. Individuals obeying local rules shaped complex group dynamics via a constant feedback loop between the individual and the group. This study could help to identify the circumstances under which particular group compositions may improve individual fitness through underlying aggregation mechanisms under specific environmental conditions.

Cancer and life-history traits: lessons from host-parasite interactions.

Despite important differences between infectious diseases and cancers, tumour development (neoplasia) can nonetheless be closely compared to infectious disease because of the similarity of their effects on the body. On this basis, we predict that many of the life-history (LH) responses observed in the context of host-parasite interactions should also be relevant in the context of cancer. Parasites are thought to affect LH traits of their hosts because of strong selective pressures like direct and indirect mortality effects favouring, for example, early maturation and reproduction. Cancer can similarly also affect LH traits by imposing direct costs and/or indirectly by triggering plastic adjustments and evolutionary responses. Here, we discuss how and why a LH focus is a potentially productive but under-exploited research direction for cancer research, by focusing our attention on similarities between infectious disease and cancer with respect to their effects on LH traits and their evolution. We raise the possibility that LH adjustments can occur in response to cancer via maternal/paternal effects and that these changes can be heritable to (adaptively) modify the LH traits of their offspring. We conclude that LH adjustments can potentially influence the transgenerational persistence of inherited oncogenic mutations in populations.

Host manipulation by cancer cells: Expectations, facts, and therapeutic implications.

Similar to parasites, cancer cells depend on their hosts for sustenance, proliferation and reproduction, exploiting the hosts for energy and resources, and thereby impairing their health and fitness. Because of this lifestyle similarity, it is predicted that cancer cells could, like numerous parasitic organisms, evolve the capacity to manipulate the phenotype of their hosts to increase their own fitness. We claim that the extent of this phenomenon and its therapeutic implications are, however, underappreciated. Here, we review and discuss what can be regarded as cases of host manipulation in the context of cancer development and progression. We elaborate on how acknowledging the applicability of these principles can offer novel therapeutic and preventive strategies. The manipulation of host phenotype by cancer cells is one more reason to adopt a Darwinian approach in cancer research.

Sexual harassment induces a temporary fitness cost but does not constrain the acquisition of environmental information in fruit flies.

Across animals, sexual harassment induces fitness costs for females and males. However, little is known about the cognitive costs involved, i.e. whether it constrains learning processes, which could ultimately affect an individual's fitness. Here we evaluate the acquisition of environmental information in groups of fruit flies challenged with various levels of male sexual harassment. We show that, although high sexual harassment induces a temporary fitness cost for females, all fly groups of both sexes exhibit similar levels of learning. This suggests that, in fruit flies, the fitness benefits of acquiring environmental information are not affected by the fitness costs of sexual harassment, and that selection may favour cognition even in unfavourable social contexts. Our study provides novel insights into the relationship between sexual conflicts and cognition and the evolution of female counterstrategies against male sexual harassment.

Ecology of information: social transmission dynamics within groups of non-social insects.

While many studies focus on how animals use public information, the dynamics of information spread and maintenance within groups, i.e. the 'ecology of information', have received little attention. Here we use fruitflies trained to lay eggs on specific substrates to implement information into groups containing both trained and untrained individuals. We quantify inter-individual interactions and then measure the spread of oviposition preference with behavioural tests. Untrained individuals increase their interactive approaches in the presence of trained individuals, and the oviposition preference transmission is directly proportional to how much trained and untrained individuals interact. Unexpectedly, the preference of trained individuals to their trained oviposition substrate decreases after interactions with untrained individuals, leading to an overall informational loss. This shows that social learning alone is not enough to support informational stability.

Social environment influences performance in a cognitive task in natural variants of the foraging gene.

In Drosophila melanogaster, natural genetic variation in the foraging gene affects the foraging behaviour of larval and adult flies, larval reward learning, adult visual learning, and adult aversive training tasks. Sitters (for(s)) are more sedentary and aggregate within food patches whereas rovers (for(R)) have greater movement within and between food patches, suggesting that these natural variants are likely to experience different social environments. We hypothesized that social context would differentially influence rover and sitter behaviour in a cognitive task. We measured adult rover and sitter performance in a classical olfactory training test in groups and alone. All flies were reared in groups, but fly training and testing were done alone and in groups. Sitters trained and tested in a group had significantly higher learning performances compared to sitters trained and tested alone. Rovers performed similarly when trained and tested alone and in a group. In other words, rovers learning ability is independent of group training and testing. This suggests that sitters may be more sensitive to the social context than rovers. These differences in learning performance can be altered by pharmacological manipulations of PKG activity levels, the foraging (for) gene's gene product. Learning and memory is also affected by the type of social interaction (being in a group of the same strain or in a group of a different strain) in rovers, but not in sitters. These results suggest that for mediates social learning and memory in D. melanogaster.

A genetic polymorphism affecting reliance on personal versus public information in a spatial learning task in Drosophila melanogaster.

Organisms that face behavioural challenges can use different types of information to guide their decisions. First, they can use the personal information they sample in their environment. Second, they can use the inadvertent social information provided by the behaviour of conspecifics or heterospecifics (i.e. public information). Currently, little is known about the interaction between genetic variation and the use of personal versus public information in natural populations. Here, we investigated whether a natural genetic polymorphism affects the use of personal versus public information in a spatial learning task in Drosophila melanogaster. We found that genetic variation at the foraging locus interacts with social context during spatial learning. While both allelic variants are able to use personal and public information to improve their navigation during 10 training trials, a probe trial revealed that individuals carrying the for(R) (rover) allele rely mainly on personal information, whereas individuals carrying the for(s) (sitter) allele either use or display more public information than rovers. Accordingly, transfer of social information is more important in groups of sitters than in groups of rovers. These results suggest that a positive feedback loop can occur between alleles promoting group living, such as for(s), and the use and/or display of public information, ultimately providing the opportunity for the joint evolution of sociality and cultural traits.

Natural variation in learning and memory.

Learning is widespread in the animal kingdom. From the small nematode worm Caenorhabditis elegans to humans, learning appears to play a central role in adaptation to local spatial and temporal environmental conditions. Though the neurobiological mechanisms of learning and memory have been intensively studied, the function and adaptive significance of learning has only recently received interest. Using learning, animals may progressively adjust their behavior in response to new environmental conditions, suggesting benefits of learning on animal performance, at least in the short term. How does learning affect the overall fitness of an animal? What are the fitness benefits and costs of learning? How can we explain the natural variation in learning ability observed between individuals, between populations of the same species or between closely related species? What are the ecological circumstances that favor the evolution of learning? There are all emerging questions that are central to a better understanding of the evolution of cognition and animal adaptation. Here I review the recent evidence showing that learning and memory are molded by an animal's lifestyle within its ecological niche.

Gene-environment interplay in Drosophila melanogaster: chronic food deprivation in early life affects adult exploratory and fitness traits.

Early life adversity has known impacts on adult health and behavior, yet little is known about the gene-environment interactions (GEIs) that underlie these consequences. We used the fruit fly Drosophila melanogaster to show that chronic early nutritional adversity interacts with rover and sitter allelic variants of foraging (for) to affect adult exploratory behavior, a phenotype that is critical for foraging, and reproductive fitness. Chronic nutritional adversity during adulthood did not affect rover or sitter adult exploratory behavior; however, early nutritional adversity in the larval period increased sitter but not rover adult exploratory behavior. Increasing for gene expression in the mushroom bodies, an important center of integration in the fly brain, changed the amount of exploratory behavior exhibited by sitter adults when they did not experience early nutritional adversity but had no effect in sitters that experienced early nutritional adversity. Manipulation of the larval nutritional environment also affected adult reproductive output of sitters but not rovers, indicating GEIs on fitness itself. The natural for variants are an excellent model to examine how GEIs underlie the biological embedding of early experience.

Functional and evolutionary trade-offs co-occur between two consolidated memory phases in Drosophila melanogaster.

Memory is a complex and dynamic process that is composed of different phases. Its evolution under natural selection probably depends on a balance between fitness benefits and costs. In Drosophila, two separate forms of consolidated memory phases can be generated experimentally: anaesthesia-resistant memory (ARM) and long-term memory (LTM). In recent years, several studies have focused on the differences between these long-lasting memory types and have found that, at the functional level, ARM and LTM are antagonistic. How this functional relationship will affect their evolutionary dynamics remains unknown. We selected for flies with either improved ARM or improved LTM over several generations, and found that flies selected specifically for improvement of one consolidated memory phase show reduced performance in the other memory phase. We also found that improved LTM was linked to decreased longevity in male flies but not in females. Conversely, males with improved ARM had increased longevity. We found no correlation between either improved ARM or LTM and other phenotypic traits. This is, to our knowledge, the first evidence of a symmetrical evolutionary trade-off between two memory phases for the same learning task. Such trade-offs may have an important impact on the evolution of cognitive capacities. On a neural level, these results support the hypothesis that mechanisms underlying these forms of consolidated memory are, to some degree, antagonistic.