1. ¹Institute of Developmental Biology and Molecular Medicine and School of Life Science, Fudan University, Shanghai 200433, China
2. ²Howard Hughes Medical Institute and Department of MCDB, University of Colorado, Boulder, CO 80309-0347, USA
3. ³Department of Immunology, Duke University Medical Center, Durham, NC 27708, USA
4. ⁴Howard Hughes Medical Institute and Department of Genetics, Yale University School of Medicine, 295 Congress Avenue, BCMM236, New Haven, CT 06536, USA

Correspondence: Kejing Deng, E-mail: dengkj@fudan.edu.cn; Tian Xu, Tel: +1-203-737-2623; Fax: +1-203-737-1762 E-mail: tian.xu@yale.edu

Received 13 June 2008; Accepted 16 June 2008.

Abstract

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.