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Learning the Shape of Evolutionary Landscapes: Geometric Deep Learning Reveals Hidden Structure in Phenotype-to-Fitness Maps

Manuel Razo-Mejia1, Madhav Mani2,3,*, and Dmitri A. Petrov1,4,5,†

  • *Contact author: madhav.mani@gmail.com
  • †Contact author: dpetrov@stanford.edu

PRX Life 4, 013030 – Published 6 March, 2026

DOI: https://doi.org/10.1103/zyj4-qt72

Abstract

Elucidating the complex relationships between genotypes, phenotypes, and fitness remains one of the fundamental challenges in evolutionary biology. Part of the difficulty arises from the enormous number of possible genotypes and the lack of understanding of the underlying phenotypic differences driving adaptation. Here we present a computational method that takes advantage of modern high-throughput fitness measurements to learn a map from high-dimensional fitness profiles to a low-dimensional latent space in a geometry-informed manner. We demonstrate that our approach using a Riemannian Hamiltonian variational autoencoder outperforms traditional linear dimensionality reduction techniques by capturing the nonlinear structure of the phenotype-fitness map. When applied to simulated adaptive dynamics, we show that the learned latent space retains information about the underlying adaptive phenotypic space and accurately reconstructs complex fitness landscapes. We then apply this method to a dataset of high-throughput fitness measurements of Escherichia coli under different antibiotic pressures and demonstrate superior predictive power for out-of-sample data compared to linear approaches. Our work provides a data-driven implementation of Fisher's geometric model of adaptation, transforming it from a theoretical framework into an empirically grounded approach for understanding evolutionary dynamics using modern deep learning methods.

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PRX Life Collection on adaptation and learning

PRX Life presents a special collection on ‘Biological systems that learn’, curated by the organizers of the National Institute for Theory and Mathematics in Biology (NITMB) workshop together with early-career researchers. The papers in this collection illustrate how living systems acquire functions, showing it is useful to describe them as tunable matter with many individually adjustable degrees of freedom characterizing microscopic properties. Drawing inspiration from AI and non-biological systems that can acquire desired functions, the featured research highlights the timeliness of the topic and its potential to drive unifying frameworks for emergent collective function in living tunable matter.

Every article in this collection is subject to a rigorous peer review process, upholding the high standards applied to all papers in the journal. The PRX Life editorial team manages peer review and makes all editorial decisions.

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