Worm Breeder's Gazette 10(3): 44

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lin-12 and glp-1 Encode Very Similar Potential Transmembrane Proteins

John Yochem and Iva Greenwald

Figure 1

The lin-12 and glp-1 genes have each been implicated in certain cell-
cell interactions during C.  elegans development (Greenwald et al., 
1983; Austin and Kimble, 1987; Priess et al., 1987).  Evidence was 
presented in the previous issue of the Gazette that these genes are 
related at the sequence level (Yochem and Greenwald, p.  84; Austin 
and Kimble, p. 85; Fire and Priess, p. 86).  The complete DNA 
sequencing of genomic and cDNA clones of glp-1 has now been finished, 
permitting an overall comparison with the complete sequence of lin-12 (
Yochem et al., 1988).  Iin-12 and glp-1 appear to have evolved from a 
common ancestor, since several splice junctions are conserved and 
their products are strikingly similar (the overall identity is about 
50%), although the glp-1 product contains only ten copies of the EGF-
like motif found 13 times in lin-12, and is therefore smaller (1295 
versus 1429 amino acids).  The predicted primary products are aligned 
below in schernatic form relative to a strongly hydrophobic stretch of 
amino acids which could serve as a membrane spanning domain.  Both 
products contain a somewhat similar sequence ('T + Y-encoded sequence')
that does not completely resemble EGF after their first copy of the 
EGF-like motif, three copies of a cysteine-rich sequence ('LNR') that 
does not resemble EGF, and six copies of a motif (Breeden and Nasmyth, 
1987) in their cytoplasmic regions that is also present in two yeast 
gene products (Schizosaccharomyces pombe cdc10, Saccharomyces 
cerevisiae SWI6).  The lin-12 and glp-1 products also have an 
intriguing overall resemblance to the product predicted for the 
Drosophila Notch gene (Wharton et al., 1985; Kidd et al., 1986 ), 
which has also been implicated in cell-cell interaction during 
development.  The lin-12 and glp-l gene products are much more closely 
related to each other than to the Notch product, and the extent of 
divergence suggests that Notch is not a counterpart of either.  A more 
reasonable consideration is that these genes define a new family with 
individual members possessing related but distinct functions during 
development.
[See Figure 1]

Figure 1