THE L(2)GL HOMOLOG 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 seq uencing of the l(2)gl gene from Drosophila pseudoobscura. comparison o f this sequence with D. melanogaster reveals a significant sequence co nservation within the l(2)gl protein-coding domain and a strong sequen ce divergence in the 5' promoter region and in the introns. The deduce d amino acid sequence of the D. pseudoobscura l(2)gl protein shows 17. 7% divergence from D. melanogaster. However, despite these evolutionar y differences, the D. pseadoobscura l(2)gl gene can fully suppress tum origenicity and restore a normal development in l(2)gl-deficient D. me lanogaster 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 patter n of expression. This shows that the highly divergent cis-regulatory e lements 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 f unction normally fulfilled by the D. melanogaster l(2)gl protein.