Dense and pleiotropic regulatory information in a developmental enhancer
| Autor: | Timothy Fuqua, Richard S. Mann, Jeff Jordan, Maria Elize van Breugel, Albert Tsai, Namiko Abe, Aliaksandr Halavatyi, Christian Tischer, Peter Polidoro, David L. Stern, Justin Crocker |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.disease_cause
Article Evolution Molecular 03 medical and health sciences 0302 clinical medicine medicine Animals Drosophila Proteins Enhancer Gene 030304 developmental biology Homeodomain Proteins Genetics Regulation of gene expression 0303 health sciences Mutation Binding Sites Multidisciplinary Base Sequence biology Gene Expression Regulation Developmental biology.organism_classification Phenotype Evolvability Drosophila melanogaster Enhancer Elements Genetic Larva Evolutionary developmental biology 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | 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. A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution. |
| Databáze: | OpenAIRE |
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