Drosophila melanogaster has been used as a model organism for experimental studies of multicellular eukaryotic biology for over a century. The group of Thomas Hunt Morgan was instrumental in developing Drosophila as an experimental system in the early 1900s. They were the first to demonstrate the linkage of genes to chromosomes, and they generated the first genetic linkage maps. In succeeding years, many groups have utilized Drosophila in studies of development, chromosome and genome biology, neurobiology and behavior, cell biology, population genetics, signal transduction, and gene regulation and function. Many significant advances in understanding the mechanisms and molecules that regulate these functions have come from Drosophila studies, as have discoveries of novel phenomena and biological processes.
The value of Drosophila as a model for other eukaryotic systems has been amply demonstrated by the fact that many genes and processes first discovered in Drosophila have proven to be conserved in other organisms, including humans. Perhaps the most striking example concerns the genes that regulate body patterning in Drosophila (the ‘homeotic’ genes), which also function in this capacity in mammals. In addition, genome projects have successfully sequenced and assembled most of the gene coding regions in flies and humans, and the comparative analysis shows that two-thirds of human disease related genes have significant Drosophila homologs.
There are many practical reasons for studying flies. There is a wealth of knowledge and tools related to Drosophila genetics, genomics, molecular biology, biochemistry, cell biology, development, and behavior, which can be used to perform experiments in a combinatorial and synergistic fashion. The entire eukaryotic component of the genome has been sequenced, assembled and annotated. Drosophila genetics is very sophisticated, and well suited for genetic screens and studies of gene interactions. Many mutations exist that affect a wide spectrum of functions, and fly genetics is facilitated by the availability of many mutations that exhibit visible phenotypes, such as eye color. Finally, biochemical and cell biological approaches are well developed and easy to utilize.
Combining different approaches provides answers that sole pursuit of an individual approach cannot accomplish. For example, despite the preeminence of molecular biology and biochemistry over the last half-century, genetics still plays a key role in the dissection of biological processes, by providing an essential link between genes, proteins, and their functions in the organism. Biochemical approaches can isolate protein complexes and subunits, and can identify protein domains with specific biochemical activities. Similarly, bioinformatics analysis of genome sequences can identify genes that encode proteins that are homologous to proteins known to play specific roles in other organisms. However, evaluating the consequences of mutating the protein, or specific domains, are necessary to determine what cellular or organismal events they regulate in the animal. Conversely, identification of a gene by isolation of a mutation that alters a specific biological process, based on phenotypic effects on the cell or the animal, does not by itself elucidate how the gene accomplishes its task at the molecular level. This is where biochemical and cell biological approaches become essential.
