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

Aguirre, Lyndsey, Hendelman, Anat, Hutton, Samuel F, McCandlish, David M, Lippman, Zachary B (October 2023) Idiosyncratic and dose-dependent epistasis drives variation in tomato fruit size. Science, 382 (6668). pp. 315-320. ISSN 0036-8075

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DOI: 10.1126/science.adi5222


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.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > quantitative biology
organism description > plant
bioinformatics > quantitative biology > quantitative genetics > quantitative epistasis
bioinformatics > quantitative biology > quantitative genetics
organism description > plant > tomato
CSHL Authors:
Communities: CSHL labs > Lippman lab
CSHL labs > McCandlish lab
School of Biological Sciences > Publications
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 20 October 2023
Date Deposited: 31 Oct 2023 19:59
Last Modified: 29 Feb 2024 18:22
PMCID: PMC10602613
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