Chronic stress response in vertebrates: The genetics of constraint and conflict

IIn biology, stress is often a poorly defined concept, and one that is negatively associated with health in humans and animals. However, stress responses actually play an important positive role in maintaining viability and health. When challenged by a threat in the environment - perhaps a predator, disturbance, or adverse conditions - a set of neuroendocrine pathways trigger physiological and behavioural responses (e.g. fight or flight behaviours) that have evolved under natural selection to counter the threat. Nonetheless, while these acute stress responses are thought to be adaptive, it is also well documented that chronic stress exposure can reduce the health of individuals and sometimes - particularly when mothers are exposed - their offspring. Because chronic stress responses, also called "tertiary stress responses" (TSR) are typically bad for fitness (survival and/or reproduction), natural selection should act over evolutionary time to get rid of them. The fact that the TSR is widespread, being found in vertebrates ranging from fish to humans, therefore poses an important question- what constrains evolution of the stress response towards a state where these harmful, or maladaptive, effects do not occur?

The goal of the proposed work is to answer this question by conducting a genetic study. We will use guppies as a model system, experimentally manipulating stressors in the environment, determining how different individuals and genotypes respond through behavioural and hormonal processes, and determining the long term consequences of this variation for fitness. In particular we will test two hypotheses about where the evolutionary constraint comes from that maintains the TSR. The first possibility is a trade-off between the effects of acute and chronic stress on fitness. In simple terms, genes that cause the TSR may persist in a population precisely because they are the ones that lead to the most appropriate acute stress responses. A second possibility is that, where mothers experience chronic stress, a trade-off occurs across the generations. Here, some maternal genotypes are better able than others to maintain the mother's own health, but do so at a cost to offspring (e.g. by reducing the amount of care she provides). Testing these hypotheses will shed light on the evolutionary processes that have shaped vertebrate stress responses in general. However, it is also expected that a better understanding of the genetics of chronic stress could yield tangible benefits for improving animal welfare in captive animal. For instance, if we understand how genes influencing aspects of the acute stress response contribute to the risk of developing disease under chronic stress, we might be able to select these traits so as to reduce health problems in livestock and aquaculture production in future.

Chronic exposure to environmental stressors can damage the fitness of individuals and their offspring. This damage occurs as a result of inappropriate expression of an individual's own stress response mechanisms, including both physiological and behavioural components. Widespread in vertebrates, this phenomenon of "tertiary stress response" cannot readily be explained by adaptive evolutionary reasoning. Here we propose to test the hypothesis that the persistence of maladaptive chronic stress responses reflects the presence of evolutionary constraint, which could arise from: i) genetically determined trade-offs between the efficacy of acute stress response pathways and the potential costs of chronic stress exposure; and/or ii) conflict between mothers and offspring over who pays the fitness costs of maternally derived stress. The project will use a fish model, combining experimental manipulation of environmental stressors with state-of-the art multivariate quantitative genetic modelling techniques. This will allow us to scrutinise the evolutionary processes that have shaped vertebrate stress responses - including our own - and evaluate the extent to which further adaptation is possible.

Although we expect the principal outputs of the research to be academic in the short term (see academic beneficiaries form), there are two additional areas in which we will seek to generate impact from the work.

1) Veterinary science, livestock industry, and government and special interest groups: Our research addresses topics of direct relevance to animal health and welfare. It will increase our understanding of how genetic factors contribute to animal performance under chronic stress conditions, a topic of particular interest to veterinary science. By testing the hypothesis of evolutionary constraint we will also quantify the potential for adaptation. This in turn will give insight into how genetic selection strategies might be applied to reduce stress-related disease in livestock production (including finfish aquaculture), an objective with clear economic and societal benefits for the UK. Finally we note that in the context of improving animal health, our results will also be of interest to governmental and non-governmental organisations with animal welfare mandates (e.g. Home Office, DEFRA, RSPCA Science Group).

2) General public: The question of how we cope with stress in our lives is one that resonates strongly with the public. Communicating the importance of this topic, and showing how evolutionary biology can contribute to our understanding of it, is another area in which we will try to generate impact beyond the immediate research community. We will seek opportunities to publicise our research and promote public understanding of (and support for) science through a variety of channels. Full details of proposed activities are given in the Pathways to Impact statement.