Zhang Jinqiu, Chen Feiyu, Li Xianghua
Zhejiang University-University of Edinburgh Institute, Zhejiang University, Haining, China.
Faculty of Biomedical Sciences, School of Medicine and Veterinary Medicine, University of Edinburgh Institute, Edinburgh, United Kingdom.
Front Genet. 2024 Feb 28;15:1366917. doi: 10.3389/fgene.2024.1366917. eCollection 2024.
Mapping genetic variations to phenotypic variations poses a significant challenge, as mutations often combine unexpectedly, diverging from assumed additive effects even in the same environment. These interactions are known as epistasis or genetic interactions. Sign epistasis, as a specific type of epistasis, involves a complete reversal of mutation effects within altered genetic backgrounds, presenting a substantial hurdle to phenotype prediction. Despite its importance, there is a limited systematic overview of the mechanistic causes of sign epistasis. This review explores the mechanistic causes, highlighting its occurrence in signalling cascades, peaked fitness landscapes, and physical interactions. Moving beyond theoretical discussions, we delve into the practical applications of sign epistasis in agriculture, evolution, and antibiotic resistance. In conclusion, this review aims to enhance the comprehension of sign epistasis and molecular dynamics, anticipating future endeavours in systematic biology engineering that leverage the knowledge of sign epistasis.
将基因变异与表型变异进行映射是一项重大挑战，因为突变常常以意想不到的方式组合，即使在相同环境中也会偏离假定的加性效应。这些相互作用被称为上位性或基因相互作用。符号上位性作为一种特定类型的上位性，涉及在改变的遗传背景下突变效应的完全逆转，这给表型预测带来了巨大障碍。尽管其很重要，但对符号上位性的机制原因的系统概述却很有限。本综述探讨了其机制原因，强调了它在信号级联、适应度峰值景观和物理相互作用中的出现。超越理论讨论，我们深入研究了符号上位性在农业、进化和抗生素抗性方面的实际应用。总之，本综述旨在增强对符号上位性和分子动力学的理解，期待未来在系统生物学工程中利用符号上位性知识的努力。
