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.

Humans Are Small, Too.

Cathy Savage, Scott R. Townsend, Yuan Tu, Richard W. Padgett

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