The interplay of additivity, dominance, and epistasis on fitness in a diploid yeast cross

We used a double barcoding system to generate and phenotype a panel of ~200,000 diploid yeast segregants that can be partitioned into hundreds of interrelated families. This experimental design enabled the detection of thousands of genetic interactions and many loci whose effects vary across families. Traits were largely specified by a small number of hub loci with major additive and dominance effects, and pervasive epistasis. Genetic background commonly influenced both the additive and dominance effects of loci, with multiple modifiers typically involved. The most prominent dominance modifier was the mating locus, which had no effect on its own. Our findings show that the interplay between additivity, dominance, and epistasis underlies a complex genotype-to-phenotype map in diploids.

本研究采用双条形码系统（double barcoding system），完成了约20万个二倍体酵母分离株的构建与表型分型，该分离株队列可被划分为数百个相互关联的家系。该实验设计支持检测数千个遗传互作位点与诸多基因座（locus，复数形式loci），这些基因座的效应在不同家系间存在显著差异。多数性状由少量枢纽基因座决定，此类基因座兼具显著的加性效应与显性效应，且存在广泛的上位性（epistasis）互作。遗传背景通常会影响基因座的加性与显性效应，且这类调控往往涉及多个修饰基因。最突出的显性效应修饰因子为交配型基因座（mating locus），其本身并不会产生独立的表型效应。本研究结果表明，加性效应、显性效应与上位性之间的相互作用，构成了二倍体生物中复杂基因型-表型映射格局的基础。