We have isolated clones from a genomic library of N2 that cross- hybridize at reduced stringency with probes from the
lin-12 gene. We sent one of the genomic clones, which had been partially sequenced to confirm that it did indeed contain a
lin-12 related gene, to Alan Coulson and John Sulston, who located the sequence on the physical map just to the right of
lin-12 by fingerprinting. The combination of map position and sequence data made us very suspicious that the cloned sequence might correspond to
glp-1, a gene that, like
lin-12, has been implicated in cell-cell interactions (Austin and Kimble, 1987; Priess et al., 1987). We sent the clone to Judith Austin and Judith Kimble, who had at about the same time by Southern blot analysis found
glp-1 allele alterations associated with cosmids in the region, and they then provided convincing evidence that our new sequence does correspond to the
glp-1 gene (see their article in this Newsletter). We also sent the clone to Andy Fire, who had been microinjecting cosmid DNA from the region in collaboration with Jim Priess (see his article in this Newsletter). DNA sequencing of both genomic and cDNA clones reveals a predicted
glp-1 product that is 50-60% identical with
lin-12 over extensive regions. Like
lin-12, the new sequence contains both EGF-like and nonEGF-like cysteine repeats in the predicted extracellular part of the protein as well as another repeated motif (also found in
cdc10, SWI6 and Notch ) in the presumed cytoplasmic portion . For example, we compare in the Figure part of the sequence encoded within a restriction fragment identified by Austin and Kimble as containing glp- 1 allele alterations with part of the ORF A exon of
lin-12 (an exon containing EGF-like repeats). These and more extensive sequence data not shown here suggest that
lin-12 and
glp-1 evolved from a common ancestor by gene duplication. Perhaps other developmentally important genes are members of this family. [See Figure 1]