A large-scale functional approach to uncover human genes and pathways in Drosophila.
We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been established. In all, 51 lines are capable of eliciting a phenotype suggesting that the human genes are functional. These heterologous genes are functionally relevant as we have found a similar mutant phenotype caused either by a dominant negative mutant form of the human ribosomal protein L8 gene or by RNAi downregulation of the Drosophila RPL8. Significantly, the Drosophila RPL8 mutant can be rescued by wild-type human RPL8. We also provide genetic evidence that Drosophila RPL8 is a new member of the insulin signaling pathway. In summary, the functions of many human genes appear to be highly conserved, and the ability to identify them in Drosophila represents a powerful genetic tool for large-scale analysis of human transcripts in vivo.
Xu
Rong
R
Institute of Developmental Biology and Molecular Medicine and School of Life Science, Fudan University, Shanghai 200433, China.
Deng
Kejing
K
Zhu
Yi
Y
Wu
Yue
Y
Ren
Jing
J
Wan
Min
M
Zhao
Shouyuan
S
Wu
Xiaohui
X
Han
Min
M
Zhuang
Yuan
Y
Xu
Tian
T
D000818:Animals; D030801:Animals, Genetically Modified; D018076:DNA, Complementary / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005796:Genes; D017344:Genes, Insect; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012269:Ribosomal Proteins / Q000235:genetics
D018076:DNA, Complementary; D012269:Ribosomal Proteins; C075184:ribosomal protein L8, rat