Wisdom from the fly.

Arguably, almost all research in Drosophila can be considered basic research, yet many of the most essential and fundamental concepts of human genetics were first decoded in the fly. Although the fly genome, which is organized into only four chromosomes, is approximately one-twentieth the size of the human genome, it contains roughly the same number of genes, and up to 75% of human disease-related genes have Drosophila homologues [1]. The fly was prized for its simplicity and utility even before such compelling homology with humans was apparent. Since Thomas Hunt Morgan began his seminal experiments over a century ago (Table 1), the Drosophila system has revealed countless key mechanisms by which cells function, including the factors that maintain chromatin and the signaling pathways that control cell fate determination and organism development. More recently, the fly has emerged as a critical neurobiological tool and disease model for a range of genetic disorders. In this review, we present a brief retrospective of Drosophila as an indispensable genetic system and discuss some of the many contributions, past and present, of this facile system to human genetics.