Linking adaptive evolution and reproductive barriers in budding yeasts

How species form is a fundamental question in biology. While species are often thought of as discrete categories, this is not always the case. Reproductive barriers prevent species from being able to make fit offspring, and they are the main mechanism that keeps species distinct. For example, donkeys and horses can mate to produce mules, a hybrid between the two, but mules are sterile and cannot produce offspring themselves. This sterility is a reproductive barrier because the mules are a "dead end" - they are not able to pass on their genes any further. Sometimes hybrids can survive and reproduce, and their offspring can be highly variable. The results can be positive, allowing species to survive extreme conditions or optimising a desirable trait for agriculture or biotechnological processes. Conversely, it can allow new diseases to emerge. Climate change, leading to unstable environmental conditions, increases the likelihood of such hybridisation events to occur. I aim to understand the factors contributing to reproductive barriers and hybridization, and why these factors exist.

There are two main types of reproductive barriers: extrinsic, resulting from the organisms' interactions with the environment, and intrinsic, resulting from the organisms themselves. It is unknown whether extrinsic and intrinsic barriers often have the same underlying causes, and this is what I want to find out.

I will harness the power of a well-established model organism, the microbial yeast Saccharomyces cerevisiae and its close relatives. These yeasts are best known for their role in biotechnology, including beer and wine fermentation, but they are also well-studied and easy to manipulate in the lab. To understand reproductive barriers in these yeasts, I will use three species that have different optimal growth temperatures (extrinsic barrier). Hybrids between these species can grow, but are largely sterile (intrinsic barrier). I will determine the genetic reasons for these two barriers to see if they are the same. First, I will find the genes responsible for growth in different temperatures. Beyond informing us about extrinsic barriers, these genes will be useful for the development of biotechnology, where optimizing growth at certain temperatures can be critical. Second, I will determine regions of the genome responsible for hybrid sterility. These types of regions are expected to be important for the existence of species of all kinds, but there are few known examples. I will then determine whether the same genes are involved in both response to temperature and hybrid sterility, and make connections between factors that underlie the existence of biological species.

This research will be carried out at the University of Exeter, a centre of excellence for studying microbial evolution. I will be embedded in a highly collaborative research environment, sharing laboratory space and resources with world-renowned experts from highly relevant disciplines. To broaden the impacts of my research, I will also be supported by a world-class group of researchers in Exeter who study fungal pathogens. Finally, I will collaborate with international colleagues Dr Gianni Liti (France), an expert on methods for determining the genes underlying complex traits, and Prof Sarah Otto (Canada), a world expert on mathematical modelling of evolutionary biology.

Climate change is a UN recognized global emergency that transcends borders. Understanding how organisms respond to changing climate, especially newly created hybrids, can impact agriculture and health through understanding of emerging fungal pathogens. By integrating information between molecular and evolutionary biology, I will advance the frontiers of bioscience discovery.

The build up of reproductive isolation (RI) is responsible for the formation of species but, when RI is incomplete, hybrids can form. Hybrids carry new trait combinations, which can create novel pathogens or biotechnologically useful organisms, and understanding RI is important for predicting their long-term fate. RI is divided into extrinsic, which is dependent on the environment, and intrinsic, which is not, but it is largely unknown if the two are linked. I aim to understand RI by determining whether there is a link between extrinsic and intrinsic RI in Saccharomyces yeasts, uncovering how that link is formed mechanistically, and predicting the evolutionary consequences.

I have recently published a novel method for creating haploid hybrids, which I will use for all pairwise crosses between three species of yeast with different temperature tolerances: Saccharomyces cerevisiae, S. paradoxus and S. kudriavzevii. I will sequence the hybrids and use them to investigate both extrinsic and intrinsic RI and how they interact.

First, I will determine how divergent temperature tolerance creates extrinsic RI by measuring the fitness and physiology of the hybrids at their parents' optimal growth temperatures and mapping the causative alleles. Using synthetically engineered strains, I will characterize the effects of the individual alleles. Second, I will determine the genomic regions that contribute to hybrid sterility (intrinsic RI) by finding genetic incompatibilities in the hybrids using a statistical method that I have developed. Finally, I will determine the link by looking for genomic co-localization and measuring hybrid sterility in the engineered temperature allele strains. I will use the results to iteratively inform mathematical models of the evolutionary consequences. This ambitious and multidisciplinary study will deepen our understanding of how hybridization can lead to emerging pathogens of both crops and animals, and can be used in biotechnology.