Andersen Erik C, Saffer Adam M, Horvitz H Robert
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Genetics. 2008 Aug;179(4):2001-12. doi: 10.1534/genetics.108.092197. Epub 2008 Aug 9.
Many mutations cause obvious abnormalities only when combined with other mutations. Such synthetic interactions can be the result of redundant gene functions. In Caenorhabditis elegans, the synthetic multivulva (synMuv) genes have been grouped into multiple classes that redundantly inhibit vulval cell fates. Animals with one or more mutations of the same class undergo wild-type vulval development, whereas animals with mutations of any two classes have a multivulva phenotype. By varying temperature and genetic background, we determined that mutations in most synMuv genes within a single synMuv class enhance each other. However, in a few cases no enhancement was observed. For example, mutations that affect an Mi2 homolog and a histone methyltransferase are of the same class and do not show enhancement. We suggest that such sets of genes function together in vivo and in at least some cases encode proteins that interact physically. The approach of genetic enhancement can be applied more broadly to identify potential protein complexes as well as redundant processes or pathways. Many synMuv genes are evolutionarily conserved, and the genetic relationships we have identified might define the functions not only of synMuv genes in C. elegans but also of their homologs in other organisms.
许多突变只有在与其他突变结合时才会导致明显的异常。这种合成相互作用可能是基因功能冗余的结果。在秀丽隐杆线虫中，合成多外阴（synMuv）基因已被分为多个类别，它们以冗余方式抑制外阴细胞命运。同一类中有一个或多个突变的动物会经历野生型外阴发育，而任何两个类别的基因都发生突变的动物则具有多外阴表型。通过改变温度和遗传背景，我们确定单个synMuv类别中大多数synMuv基因的突变会相互增强。然而，在少数情况下未观察到增强作用。例如，影响Mi2同源物和组蛋白甲基转移酶的突变属于同一类别，并未表现出增强作用。我们认为，这类基因在体内共同发挥作用，并且至少在某些情况下编码相互发生物理作用的蛋白质。遗传增强方法可以更广泛地应用于识别潜在的蛋白质复合物以及冗余的过程或途径。许多synMuv基因在进化上是保守的，我们所确定的遗传关系可能不仅定义了秀丽隐杆线虫中synMuv基因 的功能, 还定义了其他生物体中其同源物的功能。
