Worm Breeder's Gazette 12(2): 60 (January 1, 1992)

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.

HOM-C gene homologies just outside of the homeobox:

Stephen Salser, Bruce Wang, Cynthia Kenyon

Figure 1

UCSF, San Francisco, CA 94143

mab-5 belongs to a cluster of homeobox genes in C. elegans that appear to be evolutionarily related to the Antennapedia-type HOM-C genes of flies and vertebrates. All of the members of the C. elegans cluster have Antennapedia-class homeoboxes characteristic of the HOM-C genes. In addition, weak biases in these homologies suggest that the order of the genes along the chromosome may be conserved between insects, vertebrates, and nematodes. We have examined the regions just upstream and downstream of the homeobox to see if further homologies are informative.

In the following comparison we have included the Drosophila genes lab, Dfd, Antp, and AbdB; the mouse homologs Hox 2.9, Hox 2.6, Hox 2.2, and Hox 2.5, and the C. elegans genes ceh-13 , ceh-15 , mab-5 ,and ceh-11 .Comparisons are to a consensus sequence derived from these 12 genes (X is assigned to any position not conserved in greater than 33% of the proteins). Dashes indicate identity to the consensus, and gaps have been inserted to permit alignment of both the homeobox and the upstream hexapeptide motif. Identities between the C. elegans genes and their putative homologs have been boxed. (Identities not characteristic of any particular class have been boxed with a dotted line.)

[See Figure 1]

1) Homologies in the homeoboxes themselves placed the C. elegans genes into the four classes defined by the fly and vertebrate genes, however some of the assignments were weak. Furthermore, since other members of the vertebrate clusters were not included in this comparison it is possible they will provide further insight into the evolutionary relationships of the HOM-C genes.

2) A conserved hexapeptide ' VYPWMK" has been previously noted upstream of the homeoboxes of many HOM-C genes. This sequence is present upstream of genes of the lab, Dfd, and Antp classes, but is not present in genes of the AbdB class. Interestingly, this sequence is present in ceh-25 and mab-5 .We do not know if ceh-13 or ceh-11 contain this motif.

3) The region flanking the hexapeptide is rich in homologies specific to the particular gene classes. Members of the Antp class contain a proline just upstream of the hexapeptide. Members of the Dfd class contain a basic-aliphatic-histidine motif just downstream of the hexapeptide. Members of the lab class appear to instead contain a hydrophobic-lysine-arginine motif in this position.

4) The three amino acids immediately downstream of the homeobox may also be informative. AbdB and ceh-11 both contain QR following the homeobox. Members of the lab class share a glutamic acid residue.

Together, these additional homologies strengthen the argument for evolutionary conservation between worm and fly/vertebrate HOM-C clusters.

Figure 1