ANALYSIS OF MUTATIONS IN THE SQT-1 AND ROL-6 COLLAGEN GENES OF CAENORHABDITIS-ELEGANS

Different mutations in the sqt-1 and rol-6 collagen genes of Caenorhab ditis elegans can cause diverse changes in body morphology and display different genetic attributes. We have determined the nucleotide alter ations in 15 mutant alleles of these genes. Three mutations in sqt-1 a nd one in rol-6 that cause dominant right-handed helical twisting (RRo l) of animals are arginine to cysteine replacements. These mutations a re all within a short conserved sequence, on the amino terminal side o f the Gly-X-Y repeats, that is found in all C. elegans cuticle collage ns. A recessive RRol mutation of rol-6 is a replacement of one of the same conserved arginines by histidine. In contrast, three sqt-1 mutati ons that cause recessive left-handed helical twisting (LRol) are repla cements of a conserved carboxyterminal cysteine residue with either ty rosine or serine. These results suggest that disulfide bonding is impo rtant in collagen organization and that a deficit or surplus of disulf ides may cause cuticle alterations of opposite handedness. In contrast to other collagens, glycine replacement mutations in the Gly-X-Y repe ats of sqt-1 cause very mild phenotypes. Nonsense mutations of both sq t-1 and rol-6 cause nearly, but not totally, wild-type phenotypes. A n onsense mutation in sqt-1 suppresses the phenotype of rol-6 RRol mutat ions, suggesting that rol-6 collagen function is dependent on the pres ence of sqt-1 collagen. Mutations of sqt-1 are not suppressed by a rol -6 nonsense mutation, however, indicating that sqt-1 collagen can func tion independently of rol-6.