Periodic Reporting for period 1 - TRADEOFF (Deciphering fundamental constraints on pathogen adaptation)
Reporting period: 2021-09-01 to 2023-08-31
Adaptations allow organisms to better survive and reproduce in their environment. In the case of pathogenic microbes, many adaptations consist of traits that improve the pathogen’s ability to cause disease on plants and animals. Yet improving one trait often comes at expense of another, i.e. a trade-off. For example, pathogens that grow better in the absence of their host are often worse at causing disease, and vice versa. While such trade-offs between infection and survival are frequently observed, the mechanisms giving rise to such trade-offs often remain unknown. We thus lack power for predicting pathogen evolution and rarely are trade-offs exploited to contain epidemics. The overall objectives of this project were to identify underlying selective (Obj. 1), environmental (Obj. 2), and genetic (Obj. 3) constraints that together give rise to important trade-offs in fungal pathogens. Knowledge of the drivers that result in trade-offs will help inform more accurate predictions of when and where diseases will manifest and how the progression of disease might change in the future under a changing climate. A major research innovation resulting from this project was the discovery of a novel and previously unrecognized source of constraints on fungal pathogens: giant mobile elements that we named “Starships”. Through investigating the activity of Starships in various fungal pathogens, we demonstrated that Starships are associated with an important virulence-survival trade-off while at the same time they are also associated with adaptive metabolic genes and under strong negative selection. Our investigation into the association between Starships and trade-offs has revealed that Starships are a mechanism with potential to both constrain and facilitate pathogen adaptation.
We have conducted an in-depth investigation into the underlying drivers of trade-offs in fungal pathogens by examining the relationship between Starship mobile elements, virulence-survival trade-offs, and constraints on pathogen adaptation. We first developed a new, freely-available bioinformatic tool for identifying Starship elements. We then applied that tool to various fungal pathogen species to understand how Starships may be associated with selective, environmental and genetic constraints on pathogen evolution. Using population genetic analyses and meta-analyses of gene expression data, we found that Starships are under strong negative selection and that the expression of their genes changes between survival and infection conditions. We then phenotyped a fungal plant pathogen for virulence and survival related growth under changing temperature conditions, and found that Starship activity is associated with a complex, environmental-dependent trade-off between virulence and survival. Finally, we determined that many adaptive metabolic genes are carried by Starships, suggesting that they may not only constrain pathogen adaptation but also facilitate it. Together, our results have greatly increased our fundamental knowledge of why certain diseases take place while others do not. I shared our findings through a total of twelve invited seminars at international conferences and universities, thus disseminating our research to diverse communities of scientists.
The broader impacts of this project lie in the realization that fungal pathogens harbor giant mobile elements called Starships that represent unexplored sources of constraints on pathogen evolution. The principal findings of this project firmly establish a new fundamental framework for investigating the mechanisms of pathogen adaptation. Through linking the processes of mobile element activity, virulence-survival trade-offs and pathogen evolution, Starships provide striking evidence that fungal pathogen genomes are also suitable habitats for cargo-carrying elements that likely increase host adaptive potential. The identification of Starship elements unites nearly a decade’s worth of discordant observational data within the fungal literature under a single phenomenon providing a much needed perspective to the field and advancing the state of our knowledge. Their pervasive activity and associations with trade-offs challenges current expectations for how pathogens evolve, and reveals new routes through which adaptive phenotypes spread through pathogen populations.