What is it about?

Some parts of biological networks exert more regulatory control than others. Identifying these is essential to understanding biology. For instance, master regulator genes control essential cellular processes in metabolism and development, and keystone species control ecosystem stability. These key regulators have more direct, pairwise interactions with other genes or species than average, but this approach misses interactions that change in different contexts. Because context-dependent effects are prevalent in biology, we developed an approach that identifies regulators of interactions in the entire network. The approach uses the mathematical concept of epistasis on fitness landscapes. This approach reveals master regulator genes and keystone microbiome species that affect evolutionary trajectories and lifespan of the host, respectively.

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Why is it important?

Our own health and the health of our planet changes in different contexts. Determining the key regulators of biological systems at all scales is important for developing remedies when problems arise.


The Red Queen hypothesis, which was put forward in the 1970s, positioned evolution as a sort of arms race driven by competition between co-evolving species. But our work indicates that the continuous genetic innovation seen in long-term evolution experiments might not be caused by competition but could actually be due to the mutation of key genes, leading to continuous alteration of the fitness landscape.

Will Ludington
Carnegie Institution for Science

Read the Original

This page is a summary of: Master regulators of biological systems in higher dimensions, Proceedings of the National Academy of Sciences, December 2023, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2300634120.
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