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Gene networks and evolution

Samuel Scarpino

Northeastern University

The evolution of diverse phenotypes both involves and is constrained by molecular interaction networks. When these networks influence patterns of expression, we refer to them as gene regulatory networks (GRNs). Here, we develop a model of GRN evolution analogous to work from quasi-species theory, which is itself essentially the mutation–selection balance model from classical population genetics extended to multiple loci. With this GRN model, we prove that—across a broad spectrum of selection pressures—the dynamics converge to a stationary distribution over GRNs. Next, we show from first principles how the frequency of GRNs at equilibrium is related to the topology of the genotype network, in particular, via a specific network centrality measure termed the eigenvector centrality. Finally, we determine the structural characteristics of GRNs that are favoured in response to a range of selective environments and mutational constraints. Our work connects GRN evolution to quasi-species theory—and thus to classical populations genetics—providing a mechanistic explanation for the observed distribution of GRNs evolving in response to various evolutionary forces, and shows how complex fitness landscapes can emerge from simple evolutionary rules.

Samuel V. Scarpino, PhD is the Director of AI + Life Sciences at Northeastern University and a Professor of the Practice in Health and Computer Sciences. He holds appointments in the Institute for Experiential AI and the Network Science, Global Resilience, and Roux Institutes. Prior to joining Northeastern, Scarpino was the Vice President of Pathogen Surveillance at The Rockefeller Foundation. He has 10+ years of experience translating research into decision support and data science/AI tools across diverse sectors from public health and clinical medicine to real estate and energy. From 2017 to 2020, he was Chief Strategy Officer and head of data science at Dharma Platform, a social impact, technology startup, and in 2020 co-founded a data science initiative called Global.health, which was backed by Google.org and The Rockefeller Foundation. For his contributions to complex systems science, he was made a Fellow of the ISI Foundation in 2017, an External Professor at the Santa Fe Institute in 2020, and an External Faculty member of the Vermont Complex System Center in 2021.

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