Worm Breeder's Gazette 13(1): 54 (October 1, 1993)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
mab-18 is defined by two recessive mutations, bx23 and bx79 ,which cause ray 4 and ray 6 fusion in the male tail of C. elegans. After deletion analysis of a cosmid which rescues mab-18 (see Worm Meeting Abstract, 1993), we used a 5.6 kb genomic fragment as a probe to screen the Chris Martin 1-2 kb cDNA library. Five overlapping cDNAs have been isolated; each of them have different sizes varying from 1.2 kb to 1.6 kb. We completely sequenced the longest 1.6 kb cDNA and sequenced the 5' and 3' ends of the other cDNAs. From this we assembled a 1851 bp sequence which contains a 936 bp 3'-untranslated region and a poly(A) tail, but apparently without a complete 5'-end. The cDNAs cover a region of the 5.6 kb fragment essential for the rescue of mab-18 .We searched Swiss-Prot protein sequence database with the coding region. It contains a homeo domain which has 58 out of 63 (92%) amino acids identical to the homeo domain of pax-6 protein of zebrafish and human (defined in Puschel et al, Development 114, 643, 1992). 4 out of 63 are similar amino acid changes. There is only one significant difference (see alignment below). The homeo domain lies at the 5'-end of our incomplete cDNA. Similarity between the sequence 3' of the homeo domain in mab-18 and pax-6 is of unknown significance. We don't know if mab-18 is a homologue of pax-6 ,as we don't yet have the paired domain, which lies 65 amino acids 5' of the homeodomain in pax-6 of zebrafish. The homeo domain of mab-18 might be the signal detected by Burglin et al (Nature, 341:239, 1989) with degenerate oligos to the paired homeo domain. Their signal was mapped on a cosmid which overlaps with mab-18 rescuing cosmids and their degenerate sequence included part of the mab-18 homeo domain sequence.
The pax (paired box) domain was first identified as a conserved amino acid sequence motif in a class of Drosophila developmental genes which included paired, gooseberry-paired and gooseberry-distal. In mouse, eight pax genes (pax 1-8) have been isolated based on the presence of paired domains. In addition to the common paired domain, some pax genes (pax 3, 4, 6, and 7) as well as the Drosophila genes also have complete homeo domains which are closely related to each other and distinct in sequence from homeo domains of other classes of homeo box proteins. Pax genes in vertebrates are highly conserved in protein sequence and expression pattern. In particular, the protein sequences of pax-6 genes of zebrafish and mouse share 97% identity along the whole length of the protein. Pax-6 is expressed in the brain and ventral spinal cord starting in the early developing nervous system. Mutations of pax-6 in mouse (Small eye) are semidominant and homozygous lethal at birth. mab-18 was isolated by screening mutations affecting ray development. We don't know the null phenotype of mab-18 yet.
