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Fitness seascapes and the role of weak selection in adaptive evolution

Objective

A fitness landscape is like a landscape in physical space, but it maps genotypes (locations) to their fitness (elevation). The concept helps to frame Darwinian evolution as a process that drives a population towards peaks of high fitness. However, a rugged, multi-peaked landscape can prevent evolution of high fitness, because natural selection alone does not allow a population to traverse the valleys separating low from high peaks. Multiple recent experiments have revealed our ignorance about a fundamental aspect of Darwinian evolution. They show that most fitness landscapes are highly rugged, yet Darwinian evolution readily produces organisms with high fitness. SEASCAPES will study two possible solutions to this paradox. The first is environmental change, which can cause a fitness landscape to become a seascape with a dynamically changing topography. The second is weakly selected or neutral mutation – theory predicts that they can be steppingstones towards high fitness regions. My team and I will use cutting-edge experimental technology that combines high-throughput CRISPR-Cas9 genome-editing, in vivo fitness (growth rate) measurements in E. coli, and deep learning to map fitness landscapes of up to a hundred trillion (1014) genotypes, for five very different study systems that include proteins and regulatory DNA regions. We will map each landscape in two or more abiotic environments that include different carbon sources, antibiotics, and other stressors. We will join these maps with population genetic models to test three core hypotheses. First, changing environments can allow populations to discover high fitness regions even in rugged landscapes. Second, weakly selected mutations can lead to high fitness regions in such landscapes. Third, environmental change and weakly selected mutations synergize to enhance adaptive evolution. SEASCAPES will transform fitness landscape research, and resonate in fields as different as medicine and protein engineering.

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2025-ADG

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Host institution

UNIVERSITAT ZURICH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 491 985,00
Address
RAMISTRASSE 71
8006 Zurich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
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Total cost

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No data

Beneficiaries (1)