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H2020

DIET-SEX-GENOMICS Report Summary

Project ID: 708362
Funded under: H2020-EU.1.3.2.

Periodic Reporting for period 1 - DIET-SEX-GENOMICS (Linking genotype to phenotype - Role of diet on sex-specific reproduction)

Reporting period: 2016-07-01 to 2018-06-30

Summary of the context and overall objectives of the project

In this research programme, I sought to investigate the effects of nutrition on male and female behaviour and reproductive outputs. More specifically, I examined how the genetic makeup within each sex impacted nutritional needs and choices. Diet, physiology and the molecular details of nutrient signalling are the focus of much research in the biomedical field, due to their association with human life-span and health. This project created synergies between the biomedical field and evolutionary biology and will be of great impact to society. First, the data generated here on the impact of pathway manipulations on diet preference, in particular the results of single amino acid variations, will be novel and of immediate relevance to the field. Second, my work has the potential to highlight the importance of sex and inter-sexual genetic constraints. Much of the previous biomedical research has ignored the complications arising from differences between the sexes. Yet, it has been argued that sex-specific selection pressures and genetic constraints on physiological and behavioural dimorphism could contribute to the maintenance of deleterious genetic polymorphism in modern human populations. The results I will generate here will be immediately relevant to these issues. They will highlight the deleterious effects of sex-specific selection that are mediated by genetic variation in pathways that are evolutionarily conserved in sequence and function and shared between fruitflies and humans.

The objective of this research programme was to answer the following questions:
Q1. How do males and females differ in nutritional fitness effects and diet preference?
Q2. What are the genes and pathways responsible for the sexually antagonistic response to diet?

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

"The project started by performing a large experiment where I examined male and female fitness across 30 different genotypes of Drosophila. Following this large screen, we uncovered new levels of complexity in the role of diet in sex-specific fitness, revealing high levels of within-sex genetic variance underpinning nutrient-dependent fitness. These results gave rise to the first paper from this project:
• M.F. Camus, K. Fowler, M.W.D. Piper, M. Reuter (2017) Sex- and genotype-effects on nutrient-dependent fitness landscapes in Drosophila melanogaster, Proceeding of the Royal Society B, 284, 20172237

Subsequently, we aimed to explore if we saw genetic variation in dietary choice, and if reproduction played a role in nutritional choices. For this we selected a subset of genotypes from our screen and performed a diet choice experiment on mated and virgin flies from both sexes. The following publication stemmed from the results:
• M.F. Camus, CC. Huang, M. Reuter, K. Fowler (2018) ""Dietary choices are influenced by genotype, mating status and sex in Drosophila melanogaster"", Ecology & Evolution, 8:5385–5393

During the final stages of the project we aimed to examine what are the genes and pathways that respond differently in each sex. We are addressing this question using Next generation RNA Sequencing (RNA-Seq). We are currently in the process of writing up the results from this experiment into a paper (target for paper: eLife). Our findings suggest that males and female transcriptome responds very similarly changes in nutritional environment, however the reproductive genes are able to uncouple their response. In essence, reproductive genes modify nutrient signalling so that flies make choices that best suit the sex-specific tissue needs.

I have disseminated research stemming from this project at several scientific meetings. I have presented posters at the European Society of Evolutionary Biology conference (2017) and the joint European and American Evolutionary meeting (2018). Furthermore, I was invited to give a talk at the Linnaean Society as part of the “Centre for Ecology and Evolution” Autumn symposium. Finally, I have given a seminar at UCL as part of the postdoc seminar series.

During the fellowship time, I have also worked on publishing collaborative work with my previous lab and other collaborative work. A full list of my publications that have stemmed from the project can be found on my personal website and on the publication report.
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Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

Although the project funding has seized, the research programme will continue as the results stemming from this work have opened new research avenues. Dr. Florencia Camus and Dr. Max Reuter will continue to collaborate in this project and will start to further investigate the role regulatory genes play in nutritional sex-specific fitness.

The results from our programme has great impact on society by highlighting that the nutritional needs differ drastically not only between males and females, but between individuals from the same sex. Recent advances in the biomedical field have pushed for the idea of personalised medicine, whereby the genetic makeup of an individual will dictate the ideal treatment for a given pathology. We take this idea, mix it with evolutionary biology thinking, and conclude that what individuals need to maximise energy demands (via nutrition) will greatly vary. This has vital implications for metabolic diseases where certain nutrients can cause drastic physiological consequences.

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