Multiple epistatic DNA variants in a single gene affect gene expression in trans.
Multiple epistatic DNA variants in a single gene affect gene expression in trans.
复制标题
单个基因中的多个上位 DNA 变异会影响反式基因表达。
DOI：
10.1093/genetics/iyab208
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发表时间：
2022
期刊：
影响因子：
3.3
通讯作者：
Albert,FrankW
中科院分区：
文献类型：
--
作者：
Lutz,Sheila;VanDyke,Krisna;Feraru,MatthewA;Albert,FrankW
DNA variants that alter gene expression intransare important sources of phenotypic variation. Nevertheless, the identity oftrans-acting variants remains poorly understood. Single causal variants in several genes have been reported to affect the expression of numerous distant genes intrans. Whether these simple molecular architectures are representative oftrans-acting variation is unknown. Here, we studied the large RAS signaling regulator geneIRA2, which contains variants with extensivetrans-acting effects on gene expression in the yeastSaccharomyces cerevisiae. We used systematic CRISPR-based genome engineering and a sensitive phenotyping strategy to dissect causal variants to the nucleotide level. In contrast to the simple molecular architectures known so far,IRA2contained at least seven causal nonsynonymous variants. The effects of these variants were modulated by nonadditive, epistatic interactions. Two variants at the 5′-end affected gene expression and growth only when combined with a third variant that also had no effect in isolation. Our findings indicate that the molecular basis oftrans-acting genetic variation may be considerably more complex than previously appreciated.
