We have identified and cloned the Caenorhabditis elegans
dpy-2 and
dpy-10 genes and determined that they encode collagens. Genetic data suggested that these genes are important in morphogenesis and possibly other developmental events. These data include the morphologic phenotypes exhibited by mutants, unusual genetic interactions with the
sqt-1 collagen gene, and suppression of mutations in the
glp-1 and
mup-1 genes. The proximity of the
dpy-2 and
dpy-10 genes (3.5 kilobase) and the structural similarity of their encoded proteins (41% amino acid identity) indicate that
dpy-2 and
dpy-10 are the result of a gene duplication event. The genes do not, however, appear to be functionally redundant, because a
dpy-10 null mutant is not rescued by the
dpy-2 gene. In addition, full complementation between
dpy-2 and
dpy-10 can be demonstrated with all recessive alleles tested in trans. Sequence analysis of several mutant alleles of each gene was performed to determine the nature of the molecular defects that can cause the morphologic phenotypes. Glycine substitutions within the Gly-X-Y portion of the collagens can result in dumpy (Dpy), dumpy, left roller (DLRol), or temperature-sensitive DLRol phenotypes.
dpy-10(
cn64), a dominant temperature-sensitive DLRol allele, creates an Arg-to-Cys substitution in the amino non-Gly-X-Y portion of the protein. Three
dpy-10 alleles contain Tc1 insertions in the coding region of the gene.
dpy-10(
cg36) (DRLol) creates a nonsense codon near the end of the Gly-X-Y region. The nature of this mutation, combined with genetic data, indicates that DLRol is the null phenotype of
dpy-10. The Dpy phenotype results from reduced function of the
dpy-10 collagen gene. Our results indicate that a variety of molecular defects in these collagens can result in severe morphologic changes in C. elegans.