Barbazuk W B, Johnsen R C, Baillie D L
Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, Canada.
Genetics. 1994 Jan;136(1):129-43. doi: 10.1093/genetics/136.1.129.
The Caenorhabditis elegans rol-3(e754) mutation is a member of a general class of mutations affecting gross morphology, presumably through disruption of the nematode cuticle. Adult worms homozygous for rol-3(e754) exhibit rotation about their long axis associated with a left-hand twisted cuticle, musculature, gut and ventral nerve cord. Our laboratory previously isolated 12 recessive lethal alleles of rol-3. All these lethal alleles cause an arrest in development at either early or mid-larval stages, suggesting that the rol-3 gene product performs an essential developmental function. Furthermore, through the use of the heterochronic mutants lin-14 and lin-29, we have established that the expression of rol-3(e754)'s adult specific visible function is not dependent on the presence of an adult cuticle. In an attempt to understand rol-3's developmental role we sought to identify other genes whose products interact with that of rol-3. Toward this end, we generated eight EMS induced and two gamma irradiation-induced recessive suppressors of the temperature sensitive (ts) mid-larval lethal phenotype of rol-3(s1040ts). These suppressors define two complementation groups srl-1 II and srl-2 III; and, while they suppress the rol-3(s1040) lethality, they do not suppress the adult specific visible rolling phenotype. Furthermore, there is a complex genetic interaction between srl-2 and srl-1 such that srl-2(s2506) fails to complement all srl alleles tested. These results suggest that srl-1 and srl-2 may share a common function and, thus, possibly constitute members of the same gene family. Mutations in both srl-1 and srl-2 produce no obvious hermaphrodite phenotypes in the absence of rol-3(s1040ts); however, males homozygous for either srl-1 or srl-2 display aberrant tail morphology. We present evidence suggesting that the members of srl-2 are not allele specific with respect to their suppression of rol-3 lethality, and that rol-3 may act in some way to influence proper posterior morphogenesis. Finally, based on our genetic analysis of rol-3 and the srl mutations, we present a model whereby the wild-type products of the srl loci act in a concerted manner to negatively regulate the rol-3 gene.
秀丽隐杆线虫rol-3(e754)突变是影响总体形态的一类常见突变的成员，可能是通过破坏线虫的角质层来实现的。rol-3(e754)纯合的成年线虫表现出围绕其长轴的旋转，这与左手扭曲的角质层、肌肉组织、肠道和腹侧神经索有关。我们实验室先前分离出了12个rol-3的隐性致死等位基因。所有这些致死等位基因都会导致幼虫早期或中期发育停滞，这表明rol-3基因产物执行着重要的发育功能。此外，通过使用异时性突变体lin-14和lin-29，我们已经确定rol-3(e754)成年特异性可见功能的表达不依赖于成年角质层的存在。为了理解rol-3的发育作用，我们试图鉴定其他其产物与rol-3产物相互作用的基因。为此，我们产生了8个经EMS诱导和2个经γ射线照射诱导的rol-3(s1040ts)温度敏感（ts）幼虫中期致死表型的隐性抑制子。这些抑制子定义了两个互补群srl-1 II和srl-2 III；并且，虽然它们抑制rol-3(s1040)的致死性，但它们不抑制成年特异性可见滚动表型。此外，srl-2和srl-1之间存在复杂的遗传相互作用，使得srl-2(s2506)不能与所有测试的srl等位基因互补。这些结果表明srl-1和srl-2可能具有共同的功能，因此可能构成同一基因家族的成员。在没有rol-3(s1040ts)的情况下，srl-1和srl-2的突变均不会产生明显的雌雄同体表型；然而，srl-1或srl-2纯合的雄性表现出异常的尾部形态。我们提供的证据表明，srl-2的成员在抑制rol-3致死性方面并非等位基因特异性的，并且rol-3可能以某种方式影响正确的后部形态发生。最后，基于我们对rol-3和srl突变的遗传分析，我们提出了一个模型，即srl基因座的野生型产物以协同方式负调控rol-3基因。
