Idiosyncratic and dose-dependent epistasis drives variation in tomato fruit size

• 成果类型: Article
• 署名作者: Aguirre, Lyndsey; Hendelman, Anat; Hutton, Samuel F.; McCandlish, David M.; Lippman, Zachary B.
• 署名单位: Cold Spring Harbor Laboratory; Cold Spring Harbor Laboratory; State University System of Florida; University of Florida; Cold Spring Harbor Laboratory; Howard Hughes Medical Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13687
• DOI: 10.1126/science.adi5222
• 发表日期: 2023-10-20
• 页码: 315-320
• 关键词: quantitative trait variation; cryptic genetic-variation; cis-regulatory elements; molecular-mechanisms; architecture; EVOLUTION; arabidopsis; population; adaptation; redundancy

摘要

Epistasis between genes is traditionally studied with mutations that eliminate protein activity, but most natural genetic variation is in cis-regulatory DNA and influences gene expression and function quantitatively. In this study, we used natural and engineered cis-regulatory alleles in a plant stem-cell circuit to systematically evaluate epistatic relationships controlling tomato fruit size. Combining a promoter allelic series with two other loci, we collected over 30,000 phenotypic data points from 46 genotypes to quantify how allele strength transforms epistasis. We revealed a saturating dose-dependent relationship but also allele-specific idiosyncratic interactions, including between alleles driving a step change in fruit size during domestication. Our approach and findings expose an underexplored dimension of epistasis, in which cis-regulatory allelic diversity within gene regulatory networks elicits nonlinear, unpredictable interactions that shape phenotypes.