The l(2)gl homologue of Drosophila pseudoobscura suppresses tumorigenicity in transgenic Drosophila melanogaster.

Mutations in the tumour-suppressor gene lethal(2)giant larvae (l(2)gl) of Drosophila cause malignant transformation of the optic centres of the larval brain and the imaginal discs. We report the cloning and sequencing of the l(2)gl gene from Drosophila pseudoobscura. Comparison of this sequence with D. melanogaster reveals a significant sequence conservation within the l(2)gl protein-coding domain and a strong sequence divergence in the 5' promoter region and in the introns. The deduced amino acid sequence of the D. pseudoobscura l(2)gl protein shows 17.7% divergence from D. melanogaster. However, despite these evolutionary differences, the D. pseudoobscura l(2)gl gene can fully suppress tumorigenicity and restore a normal development in l(2)gl-deficient D. melanogaster flies, although the rescued animals display poor viability and fertility. Furthermore, in D. melanogaster transgenic flies, the D. pseudoobscura l(2)gl protein is produced at a similar level as the D. melanogaster l(2)gl protein and displays an identical spatial pattern of expression. This shows that the highly divergent cis-regulatory elements of the D. pseudoobscura transgene can be fully recognized in D. melanogaster and lead to the synthesis of a transgenic protein that has enough specificity conserved for replacing the tumour-suppressor function normally fulfilled by the D. melanogaster l(2)gl protein.