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Adaptive Ratchets and the Evolution of Molecular Complexity

Tom Röschinger1, Roberto Morán-Tovar2, Simone Pompei3, and Michael Lässig2,*

  • *Contact author: mlaessig@uni-koeln.de
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PRX Life 4, 023004 – Published 9 April, 2026

DOI: https://doi.org/10.1103/bhf2-3v22

Abstract

Biological systems have evolved to amazingly complex states, yet we do not understand in general how evolution operates to generate increasing genetic and functional complexity. Molecular recognition sites are short genome segments or peptides that can bind a cognate recognition target of sufficient sequence similarity, thereby inducing a target-dependent function. Such sites are simple, ubiquitous modules of sequence information, cellular physiology, and evolution. Here we show that recognition sites, if coupled to a time-dependent recognition target, can rapidly evolve to complex states with larger code length and smaller coding density than sites recognizing a static target. Such processes take place in a new mode of molecular evolution called an adaptive ratchet, characterized by asymmetric selection for code extensions and compressions. The underlying evolutionary model contains selection for recognition depending on the site-target binding affinity and mutations with a separation of timescales between changes of binding function and complexity changes. We show that ratchet evolution increases the number of mutational paths available for adaptive code changes, thereby accelerating the response to moving targets and facilitating refinement and innovation of recognition functions. We apply these results to the recognition of fast-evolving antigens by the human immune system. Our analysis shows how molecular complexity can evolve as a collateral to selection for function in a dynamic environment.

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PRX Life 4, 023004– Published 9 April, 2026
  • Received 24 December 2024
  • Accepted 13 March 2026
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