Noble Luke M, Miah Asif, Kaur Taniya, Rockman Matthew V
Institut de Biologie, École Normale Supérieure, CNRS 8197, Inserm U1024, PSL Research University, F-75005 Paris, France
Center for Genomics and Systems Biology, Department of Biology, New York University, NY, 10003.
G3 (Bethesda). 2020 Jul 7;10(7):2385-2395. doi: 10.1534/g3.120.401336.
Genetic background commonly modifies the effects of mutations. We discovered that worms mutant for the canonical gene, identified by Brenner in 1974, do not roll in the genetic background of the wild strain CB4856. Using linkage mapping, association analysis and gene editing, we determined that N2 carries an insertion in the collagen gene that acts as a recessive enhancer of rolling. From population and comparative genomics, we infer the insertion is derived in N2 and related laboratory lines, likely arising during the domestication of , and breaking a conserved protein. The ancestral version of also modifies the phenotypes of four other classical cuticle mutant alleles, and the effects of natural genetic variation on worm shape and locomotion. These results underscore the importance of genetic background and the serendipity of Brenner's choice of strain.
遗传背景通常会改变突变的影响。我们发现，1974年由布伦纳鉴定出的经典基因发生突变的线虫，在野生菌株CB4856的遗传背景中不会翻滚。通过连锁图谱分析、关联分析和基因编辑，我们确定N2在胶原蛋白基因中存在一个插入片段，该片段作为翻滚的隐性增强子。从群体和比较基因组学中，我们推断该插入片段在N2及相关实验室品系中衍生而来，可能在该品系驯化过程中出现，并破坏了一种保守蛋白。该基因的祖先版本还会改变其他四个经典表皮突变等位基因的表型，以及自然遗传变异对线虫形状和运动的影响。这些结果强调了遗传背景的重要性以及布伦纳选择菌株的偶然性。
