Török I, Hartenstein K, Kalmes A, Schmitt R, Strand D, Mechler B M
Department of Developmental Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Oncogene. 1993 Jun;8(6):1537-49.
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.
果蝇肿瘤抑制基因致死（2）巨幼虫（l(2)gl）的突变会导致幼虫大脑视中枢和成虫盘的恶性转化。我们报告了从拟暗果蝇中克隆和测序l(2)gl基因的情况。将该序列与黑腹果蝇进行比较，发现在l(2)gl蛋白质编码域内有显著的序列保守性，而在5'启动子区域和内含子中有很强的序列差异。拟暗果蝇l(2)gl蛋白的推导氨基酸序列与黑腹果蝇相比有17.7%的差异。然而，尽管存在这些进化差异，拟暗果蝇l(2)gl基因仍能完全抑制致瘤性，并在l(2)gl缺陷的黑腹果蝇中恢复正常发育，尽管获救的动物生存力和繁殖力较差。此外，在黑腹果蝇转基因果蝇中，拟暗果蝇l(2)gl蛋白的产生水平与黑腹果蝇l(2)gl蛋白相似，并显示出相同的空间表达模式。这表明拟暗果蝇转基因中高度 divergent 的顺式调控元件在黑腹果蝇中能被完全识别，并导致合成一种具有足够保守特异性的转基因蛋白，以取代通常由黑腹果蝇l(2)gl蛋白履行的肿瘤抑制功能。 （注：原文中“divergent”未准确翻译，推测是想表达“不同的、有差异的”之类意思，这里按此理解翻译为“divergent 的顺式调控元件”，但需结合原文更准确语境确定其确切含义）
