Worm Breeder's Gazette 13(5): 74 (February 1, 1995)
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.
Waksman Institute, Piscataway, NJ 08855
In the last gazette, we reported evidence that sma-2 and sma-4 encode novel, but related, TGF-b signalling components that act in the same pathway as the BMP receptor, daf-4. We also noted that one other sequence was present in the database which showed a high degree of similarity with these two genes, particularly with sma-2. Since this third homolog mapped to the predicted location of sma-3, which acts in the same signalling pathway as sma-2 and sma-4, we hypothesized that sma-3 also encodes a related signalling molecule. We have now shown that the cosmid R13F6 that contains the predicted homolog can rescue a sma-3 mutant, lending support to our hypothesis. Final verification awaits the identification of molecular lesions in sma-3 alleles. More recent database searches have revealed that this gene family is not limited to the nematode. A random human cDNA sequence reported by Genethon, France represents the first identified vertebrate member (see Figure). Although the sequence contains only ca.55 amino acids, the homology is readily apparent (~80percent similar to sma-2). Also of interest is a recently reported Drosophila gene, Mothers against dpp (Mad) (Sekelsky et al, Genetics, in press; J. Sekelsky and W. Gelbart, pers.comm.). This gene was identified in Dr. Gelbart's lab in two different genetic screens for modifiers of dpp (a TGF-b like ligand). The phenotypic characterization of Mad shows that it acts in the dpp signalling pathway; its sequence illustrates that it encodes another homolog of SMA-2, SMA-3, and SMA-4 (-70percent similar to sma-2 for over 400 amino acids). This result reinforces the hypothesis that these proteins function in TGF-b signalling pathways. The sequences of the identified fly and human homologs are more similar to sma-2 than to sma-3; and sma-4 encodes an even more divergent homolog. This analysis suggests that these genes diverged before the divergence of worm, flies, and humans, and makes it likely that multiple homologs will be present in these and other organisms as well. We have considered naming this family the SMALL proteins or the MAD proteins, but each of this names may be ambiguous. Specifically, there are other sma genes in C. elegans that have not yet been cloned and are likely to encode unrelated products; and there is also a family of proteins identified by their common MADS box motif. Instead, we propose the term DWARFIN for this family of gene products, in reference to the Small phenotype associated with these genes in C elegans.