The UNC-119 family of neural proteins is functionally conserved between humans, Drosophila and C-elegans

C. elegans animals mutant for the unc-119 gene exhibit movement, sensory an d behavioral abnormalities. Consistent with a nervous system role, unc-119 reporter genes are expressed throughout the C. elegans nervous system. The UNC-119 protein has strong sequence similarity to the predicted protein fro m a human gene, HRG4/HsUNC-119, whose transcript is abundant in the retina. Using these similarities, we have identified a Drosphila homolog. DmUNC-11 9, which is expressed in the Drosophila nervous system. The pre-dieted C. e legans, human and Drosophila gene products are conserved across two domains . Expression of portions of HRG4/HsUNC-119 or DmUNC-119, directed by the un c-119 promoter, can fully rescue the C. elegans unc-119 mutant phenotype. W e rested the ability of portions of HRG4/HsUNC-119 to rescue, and found tha t its function in C. elegans requires the conserved carboxyl terminus, whil e the dissimilar amino terminus is dispensable. UNC-119, HRG4 and DmUNC-119 constitute members of a new class of neural genes whose common function ha s been maintained through metazoan evolution.