Dense and pleiotropic regulatory information in a developmental enhancer

Timothy Fuqua, Jeff Jordan, Maria Elize Breugel, Aliaksandr Halavatyi, Christian Tischer, Peter Polidoro, Namiko Abe, Albert Tsai, Richard S. Mann, David L. Stern () and Justin Crocker ()
Additional contact information
Timothy Fuqua: European Molecular Biology Laboratory
Jeff Jordan: Janelia Research Campus
Maria Elize Breugel: European Molecular Biology Laboratory
Aliaksandr Halavatyi: European Molecular Biology Laboratory
Christian Tischer: European Molecular Biology Laboratory
Peter Polidoro: Janelia Research Campus
Namiko Abe: Columbia University
Albert Tsai: European Molecular Biology Laboratory
Richard S. Mann: Columbia University
David L. Stern: Janelia Research Campus
Justin Crocker: European Molecular Biology Laboratory

Nature, 2020, vol. 587, issue 7833, 235-239

Abstract: Abstract Changes in gene regulation underlie much of phenotypic evolution1. However, our understanding of the potential for regulatory evolution is biased, because most evidence comes from either natural variation or limited experimental perturbations2. Using an automated robotics pipeline, we surveyed an unbiased mutation library for a developmental enhancer in Drosophila melanogaster. We found that almost all mutations altered gene expression and that parameters of gene expression—levels, location, and state—were convolved. The widespread pleiotropic effects of most mutations may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse Drosophila larvae revealed apparent biases in the phenotypes influenced by the enhancer. Developmental enhancers may encode a higher density of regulatory information than has been appreciated previously, imposing constraints on regulatory evolution.

Date: 2020
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DOI: 10.1038/s41586-020-2816-5

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