David J. Jordan | Searcharxiv

arXiv2023

Canalisation and plasticity on the developmental manifold of Caenorhabditis elegans

How do the same mechanisms that faithfully regenerate complex developmental programs in spite of environmental and genetic perturbations also permit responsiveness to environmental signals, adaptation, and genetic evolution? Using the nematode Caenorhabditis elegans as a model, we explore the phenotypic space of growth and development in various genetic and environmental contexts. Our data are growth curves and developmental parameters obtained by automated microscopy. Using these, we show that among the traits that make up the developmental space, correlations within a particular context are predictive of correlations among different contexts. Further we find that the developmental variability of this animal can be captured on a relatively low dimensional phenoptypic manifold and that on this manifold, genetic and environmental contributions to plasticity can be deconvolved independently. Our perspective offers a new way of understanding the relationship between robustness and flexibility in complex systems, suggesting that projection and concentration of dimension can naturally align these forces as complementary rather than competing.

q-bio.QM↗

arXiv2022

Processive and Distributive Non-Equilibrium Networks Discriminate in Alternate Limits

We study biochemical reaction networks capable of product discrimination inspired by biological proofreading mechanisms. At equilibrium, product discrimination, the selective formation of a "correct" product with respect to an "incorrect product", is fundamentally limited by the free energy difference between the two products. However, biological systems often far exceed this limit, by using discriminatory networks that expend free energy to maintain non-equilibrium steady states. Non-equilibrium systems are notoriously difficult to analyze and no systematic methods exist for determining parameter regimes which maximize discrimination. Here we introduce a measure that can be computed directly from the biochemical rate constants and which provides a necessary condition for proofreading. Non-equilibrium systems can discriminate using binding energy (energetic) differences or using activation energy (kinetic) differences, but in both cases, proofreading is optimal when dissipation is maximized, so long as the necessary condition we introduce is satisfied. We show that these constraints can be in opposition and that this explains why the error rate is a non-monotonic function of the irreversible drive in the original proofreading scheme of Hopfield and Ninio. Finally, we introduce mixed networks, in which one product is favored energetically and the other kinetically. In such networks, sensitive product switching can be achieved simply by spending free energy. Biologically, this corresponds to the ability to select between products by driving a single reaction without network fine tuning. This may be used to explore alternate product spaces in challenging environments.

physics.bio-ph↗