The Puzzle of Fitness Landscapes

The European Research Council’s ERC Advanced Grants are among Europe’s most prestigious research awards. They support established researchers with outstanding scientific track records. Evolutionary biologist and UZH professor Andreas Wagner has been awarded one of these grants for his research project Fitness Seascapes and the Role of Weak Selection in Adaptive Evolution. The project will receive EUR 2.5 million in funding.

Over the next five years, Wagner and his team will investigate fundamental questions of biological fitness. In this context, “fitness” refers not to physical performance, but to evolutionary success: how well can an organism survive and pass on its genes to future generations?

The research project focuses on fitness landscapes, a central concept in evolutionary biology. In these landscapes, genetic variants are mapped out across an abstract surface and represented as elevation. “A fitness landscape is analogous to a landscape in physical space,” says Wagner. “Each location represents a genotype, a genetic variant. The elevation shows its ability to survive and reproduce – in other words, its biological fitness.” This concept helps frame evolution as a process that drives a population toward peaks of high fitness.

“Several recent experiments have shown that our understanding of a fundamental aspect of Darwinian evolution is inadequate,” says Wagner. This is because most fitness landscapes are highly rugged. Evolution would therefore often get stuck on a low peak, even though there are higher ones nearby. However, Darwinian evolution readily produces organisms with high fitness.

The Seascapes project will study two possible solutions to this paradox. The first is environmental change, which can transform a static fitness landscape into one with a dynamically changing topography – such as a seascape with constantly shifting wave crests and troughs. The second is neutral mutation, which does not alter fitness, but can serve as a steppingstone toward high fitness regions, allowing organisms to bypass lower peaks.

The researchers will use cutting-edge technologies, including genome editing and artificial intelligence (AI), to map the fitness landscapes of up to 100 trillion genotypes. Their analyses will be conducted for five very different study systems, including proteins and regulatory DNA regions. The research team will map each landscape in two or more environments that contain different carbon sources, antibiotics and other stressors, and they will then combine these maps with population genetic models to test three core hypotheses. Wagner’s ambitions for the project are high: “The Seascapes project could fundamentally change our understanding of evolution and resonate in fields as different as medicine and protein engineering.”