Understanding the evolution of nutritional adaptation

The world is changing in complex ways. This change forces organisms to cope with shifts in their environmental conditions, the footprint of which can be seen across multiple scales. Environmental change will not only increase global temperatures, but also alter the distribution and nutritional composition of plants and other primary products. Changes in food quality and quantity will undoubtedly affect require organisms to metabolically adapt to these new conditions. Mitochondria are central to metabolic adaptation as they are the hub that converts food into energy (used to survive and reproduce). This process is regulated via a series of finely coordinated interactions encoded by two obligate genomes - nuclear and mitochondrial. Both genomes are required for the production of cellular energy, and thus their harmonious interaction is vital for the maintenance of mitochondrial integrity. Changing the nutritional composition of an organism can have a great impact on mitochondrial functioning; altering the production of mitochondrial metabolites, which ultimately impacts the ability for a species to persist. It is imperative that we understand how these two genomes can constrain the ability for an organism adapt to new environments.

By combining my expertise in evolutionary biology, physiology and population genetics, I will be able to address these fundamental questions. What I first aim to examine is how changing nutrition and our genes can impact fitness. For this I will harness the power of the model organism Drosophila melanogaster (fruit fly). One of the great benefits of using the fruit fly system is that we can genetically manipulate the mitochondrial and the nuclear genomes, providing a clean system to study what happens when these genomes do not work well together. I have already created a panel of 81 fly lines that have either coevolved (normal) or mismatched genomes. I will characterise both what these fly strains need to eat to maximise fitness, and also what they chose to eat if they are given a choice.

I will then uncover what are the genes/pathways responsible for differences in nutritional fitness optima. Using a powerful combination of RNASeq and metabolomics, I will get insights into how nutrition affects different metabolic pathways, and these genes influence what metabolic pathways are used. Next-generation sequencing will be complimented with tissue-specific respirometry to determine mitochondrial function, which will allow me to uncover physiological responses to diet. In addition, I will be able to detect signature of metabolic stress, and examine how different diets alleviate the stress. As a consequence, this objective will give provide a deeper knowledge the molecular mechanisms of metabolic adaptation.

Finally, to fully understand the evolutionary consequences of diet and mito-nuclear interactions on metabolic function, it is necessary to gain insights into the persistence of mito-nuclear variation. By investigating how mitochondrial and nuclear genetic variation evolves, we will be able to better understand the constraints on metabolism. Consequently, for this objective I will aim to test here whether diet causes selective advantages of certain mito-nuclear combinations, using a long-term multi-generational framework. This will enable me to track nuclear gene frequency changes through time (generations) when placed alongside a particular mitochondrial haplotype and across different nutritional regimes. I expect that flies with better coadapted mito-nuclear interactions will persist through time and I predict that persistence of a haplotype will be diet dependent. This is because certain dietary regimes will place greater/reduced selection intensity on the optimal functioning of the OXPHOS system. Taken together, these objectives will greatly enhance our basic understanding about nutritional adaptation and provide a framework to apply these concepts to natural populations.