Widespread epistasis among beneficial genetic variants revealed by high-throughput genome editing
Widespread epistasis among beneficial genetic variants revealed by high-throughput genome editing
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DOI：
10.1016/j.xgen.2023.100260
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发表时间：
2023-04-12
期刊：
影响因子：
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通讯作者：
Fraser, Hunter B.
中科院分区：
文献类型：
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作者：
Ang, Roy Moh Lik;Chen, Shi-An A.;Fraser, Hunter B.
任何遗传变异的表型效应都可以通过其他基因组位点的变异来改变。这些遗传相互作用被称为上位性，它们塑造了每个物种的基因型-表型图，但它们的起源仍然知之甚少。为了研究这一点，我们采用高通量基因组编辑来测量四种酿酒酵母菌株中1，826种天然多态性变体的适应性效应。大约31%的变异影响适应性，其中24%具有指示上位性的菌株特异性适应性效应。我们发现，有益的变体更有可能表现出遗传相互作用，并且这些相互作用可以通过特定的性状如絮凝能力来介导。这项工作表明，适应性进化往往涉及权衡，其中一个变体只在某些遗传背景中是有益的，这可能解释了为什么许多有益的变体仍然是多态的。总之，我们提供了一个框架，以了解影响单核苷酸分辨率上位性的因素，揭示了广泛的上位性之间的有益的变异。
The phenotypic effect of any genetic variant can be altered by variation at other genomic loci. Known as epistasis, these genetic interactions shape the genotype-phenotype map of every species, yet their origins remain poorly understood. To investigate this, we employed high-throughput genome editing to measure the fitness effects of 1,826 naturally polymorphic variants in four strains of Saccharomyces cerevisiae. About 31% of variants affect fitness, of which 24% have strain-specific fitness effects indicative of epistasis. We found that beneficial variants are more likely to exhibit genetic interactions and that these inter-actions can be mediated by specific traits such as flocculation ability. This work suggests that adaptive evolution will often involve trade-offs where a variant is only beneficial in some genetic backgrounds, potentially explaining why many beneficial variants remain polymorphic. In sum, we provide a framework to understand the factors influencing epistasis with single-nucleotide resolution, revealing widespread epistasis among beneficial variants.