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| Main Authors: | , , , , |
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| Format: | Preprint |
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2025
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| Subjects: | |
| Online Access: | https://arxiv.org/abs/2507.11973 |
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| _version_ | 1866916845602209792 |
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| author | Russo, Christopher Joel Husain, Kabir Ranganathan, Rama Pincus, David Murugan, Arvind |
| author_facet | Russo, Christopher Joel Husain, Kabir Ranganathan, Rama Pincus, David Murugan, Arvind |
| contents | Biological systems, with many interacting components, face high-dimensional environmental fluctuations, ranging from diverse nutrient deprivations to toxins, drugs, and physical stresses. Yet, many biological control mechanisms are `simple' -- they restore homeostasis through low-dimensional representations of the system's high-dimensional state. How do low-dimensional controllers maintain homeostasis in high-dimensional systems? We develop an analytically tractable model of integral feedback for complex systems in fluctuating environments. We find that selection for homeostasis leads to the emergence of a soft mode that provides the dimensionality reduction required for the functioning of simple controllers. Our theory predicts that simple controllers that buffer environmental perturbations (e.g., stress response pathways) will also buffer mutational perturbation, an equivalence we test using experimental data across ~5000 strains in the yeast knockout collection. We also predict, counterintuitively, that knocking out a simple controller will \emph{decrease} the dimensionality of the response to environmental change; we outline transcriptomics tests to validate this. Our work suggests an evolutionary origin of soft modes whose function is for dimensionality reduction in and of itself rather than direct function like allostery, with implications ranging from cryptic genetic variation to global epistasis. |
| format | Preprint |
| id |
arxiv_https___arxiv_org_abs_2507_11973 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Simple biological controllers drive the evolution of soft modes Russo, Christopher Joel Husain, Kabir Ranganathan, Rama Pincus, David Murugan, Arvind Biological Physics Biological systems, with many interacting components, face high-dimensional environmental fluctuations, ranging from diverse nutrient deprivations to toxins, drugs, and physical stresses. Yet, many biological control mechanisms are `simple' -- they restore homeostasis through low-dimensional representations of the system's high-dimensional state. How do low-dimensional controllers maintain homeostasis in high-dimensional systems? We develop an analytically tractable model of integral feedback for complex systems in fluctuating environments. We find that selection for homeostasis leads to the emergence of a soft mode that provides the dimensionality reduction required for the functioning of simple controllers. Our theory predicts that simple controllers that buffer environmental perturbations (e.g., stress response pathways) will also buffer mutational perturbation, an equivalence we test using experimental data across ~5000 strains in the yeast knockout collection. We also predict, counterintuitively, that knocking out a simple controller will \emph{decrease} the dimensionality of the response to environmental change; we outline transcriptomics tests to validate this. Our work suggests an evolutionary origin of soft modes whose function is for dimensionality reduction in and of itself rather than direct function like allostery, with implications ranging from cryptic genetic variation to global epistasis. |
| title | Simple biological controllers drive the evolution of soft modes |
| topic | Biological Physics |
| url | https://arxiv.org/abs/2507.11973 |