Throughout the course of this project, we made significant strides in understanding evolutionary processes through the study of fitness landscapes. Our research aimed to quantify how mutations, hybridization, and other mechanisms affect adaptation and speciation across biological scales and environmental conditions. This work, which spanned both theoretical and empirical approaches, has resulted in substantial contributions to the field of evolutionary biology, culminating in a total of 25 peer-reviewed publications related to the project, and more than 60 talks and 10 posters with which the PI and her team members presented the work at seminars and conferences.
The project focused on four main aims, each of which was integral to advancing our understanding of evolutionary dynamics. These aims covered a wide spectrum of topics, from quantifying the fitness effects of mutations to studying hybridization dynamics and non-standard forms of adaptation.
Aims 1 and 2: Fitness Landscapes Across Biological Levels and Environments
Our first focus was to quantify fitness landscapes across biological scales and environmental conditions. In this context, we examined the distribution of fitness effects of new mutations in the heat-shock protein Hsp90 under various environmental conditions (Cote-Hammarlof, Fragata et al., MBE, 2021; Flynn et al., eLife, 2020). Notably, our work revealed that regions of the protein showing fitness effects from mutations did not necessarily align with known structural features, such as active sites. This finding emphasizes the complexity of fitness landscapes and the potential for unexpected mutational effects.
We also explored the fitness effects of antimicrobial resistance mutations in E. coli under different genetic backgrounds and environmental conditions. This research uncovered a significant degree of epistasis, especially in non-standard environments (Hinz et al., MBE, 2024), while showing relatively little epistasis across temperature gradients (Ghenu et al., Phil Trans B, 2023). Additionally, we developed mathematical theory that critically assesses microbial growth models and inference methods (Ghenu, Marrec, et al., Frontiers in Ecology and Evolution, 2024; Marrec et al., Ecology and Evolution, 2023).
Aim 3: Mechanisms of Adaptation
In this Aim of the project, we explored different adaptation mechanisms, including modifiers of epistasis and mutation rates, to quantify how they may influence evolutionary dynamics. A noteworthy empirical finding was that the mutational load of bacteria in the mouse gut remains low even in the presence of mutator genotypes, indicating that weak selection dominates during the adaptation of bacteria in the mouse gut (Ramiro et al., Plos Biology, 2020). We also discovered that epigenetic mechanisms in yeast can provide a selective advantage in fluctuating environments (Stajic et al., GBE, 2021).
Our theoretical work extended to models of chromosomal inversions, demonstrating that small-effect deleterious mutations can accumulate rapidly in inversions, potentially leading to recessive lethal systems (Berdan et al., Plos Genetics, 2021). Furthermore, we developed and analyzed models of how populations under high mutation pressure could avoid extinction through evolutionary rescue mechanisms (Bank et al., Frontiers in Virology, 2023).
Aim 4: Hybridization Dynamics
The consequences of epistasis during hybridization were the final central theme of this project. Here, we developed new models to understand how hybridization influences evolutionary trajectories. For instance, we demonstrated that cryptic epistasis in fitness landscapes could enable speciation even in the presence of gene flow (Blanckaert et al., Phil Trans B, 2020). We also examined the extinction probability of hybrid populations, showing that genomic architecture plays a critical role in hybrid survival (Blanckaert et al., Evolution, 2023).
Our methodological innovations in this Aim extended to statistical approaches. We developed a method to detect hybrid incompatibilities using genomic data, which we applied to studies of fish hybrid populations (Li et al., Plos Genetics, 2022). Our new method overcomes the limitations of previous approaches by distinguishing between linkage disequilibrium from physical linkage and from hybrid incompatibilities, providing a promising tool for the identification of intrachromosomal hybrid incompatibilities.
