TY - JOUR T1 - Dense encoding of developmental regulatory information may constrain evolvability JF - bioRxiv DO - 10.1101/2020.04.17.046052 SP - 2020.04.17.046052 AU - Timothy Fuqua AU - Jeff Jordan AU - Maria Elize van Breugel AU - Aliaksandr Halavatyi AU - Christian Tischer AU - Peter Polidoro AU - Namiko Abe AU - Albert Tsai AU - Richard S. Mann AU - David L. Stern AU - Justin Crocker Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/04/18/2020.04.17.046052.abstract N2 - Gene regulatory changes underlie much of phenotypic evolution. However, the evolutionary potential of regulatory evolution is unknown, because most evidence comes from either natural variation or limited experimental perturbations. Surveying an unbiased mutation library for a developmental enhancer in Drosophila melanogaster using an automated robotics pipeline, we found that most mutations alter gene expression. Our results suggest that regulatory information is distributed throughout most of a developmental enhancer and that parameters of gene expression—levels, location, and state—are convolved. The widespread pleiotropic effects of most mutations and the codependency of outputs may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse drosophilids reveal mainly stasis and apparent biases in the phenotypes influenced by this enhancer. Developmental enhancers may encode a much higher density of regulatory information than has been appreciated previously, which may impose constraints on regulatory evolution.Quote “Rock, robot rockRock, robot rockRock, robot rock”Daft Punk (2005)Competing Interest StatementThe authors have declared no competing interest. ER -