瑞士洛桑大学Sebastian Soyk研究组运用碱基编辑，修复了番茄花调节基因中的有害驯化突变。相关论文于2025年1月2日发表于国际学术期刊《自然—遗传学》杂志。

研究人员发现番茄转录因子SP2抑制因子（SSP2）中的有害突变，这种突变在驯化种质中非常普遍，并削弱了DNA与全基因组靶标的结合。研究发现，在调节芽和花序结构的过程中，SSP2的作用与其同系物SSP的作用存在部分冗余。

然而，冗余性在番茄驯化过程中受到影响，该现象在近缘物种Physalis grisea中则完全丧失，在该物种中，只有一个直向同源物调控嫩枝分枝。研究人员应用碱基编辑技术直接修复了栽培番茄中的有害突变，获得的植株生长紧凑，果实产量较高。该工作证明有害变异导致现有基因型对表型调整敏感的原因，并解释了基因组编辑修复有害突变是如何实现可预测作物改良的。

据悉，作物基因组会积累有害突变-这种现象被称为驯化成本。曾设想通过精准基因组编辑来消除这些潜在的有害突变，但目前还缺乏相应的实验报道。

附：英文原文

Title: Repairing a deleterious domestication variant in a floral regulator gene of tomato by base editing

Author: Glaus, Anna N., Brechet, Marion, Swinnen, Gwen, Lebeigle, Ludivine, Iwaszkiewicz, Justyna, Ambrosini, Giovanna, Julca, Irene, Zhang, Jing, Roberts, Robyn, Iseli, Christian, Guex, Nicolas, Jimnez-Gmez, Jos, Glover, Natasha, Martin, Gregory B., Strickler, Susan, Soyk, Sebastian

Issue&Volume: 2025-01-02

Abstract: Crop genomes accumulate deleterious mutations—a phenomenon known as the cost of domestication. Precision genome editing has been proposed to eliminate such potentially harmful mutations; however, experimental demonstration is lacking. Here we identified a deleterious mutation in the tomato transcription factor SUPPRESSOR OF SP2 (SSP2), which became prevalent in the domesticated germplasm and diminished DNA binding to genome-wide targets. We found that the action of SSP2 is partially redundant with that of its paralog SSP in regulating shoot and inflorescence architecture. However, redundancy was compromised during tomato domestication and lost completely in the closely related species Physalis grisea, in which a single ortholog regulates shoot branching. We applied base editing to directly repair the deleterious mutation in cultivated tomato and obtained plants with compact growth that provide an early fruit yield. Our work shows how deleterious variants have sensitized modern genotypes for phenotypic tuning and illustrates how repairing deleterious mutations with genome editing may allow predictable crop improvement.

DOI: 10.1038/s41588-024-02026-9

Source: https://www.nature.com/articles/s41588-024-02026-9