Fruit Fly: Drosophila

Drosophila melanogaster, a common fruit fly, was one of the first model organisms used in genetic research, and continues to be one of the most important. Thomas Hunt Morgan (1866-1945) developed Drosophila as a model system in 1909. Morgan, along with his students, Calvin Bridges, Alfred Sturtevant, and Hermann Muller, made some of the most important discoveries in genetics through their work with Drosophila. Among these were the genetic explanation of sex linkage (the location of a gene on a sex chromosome); proof that genes are contained on chromosomes; and the demonstration that genes are arranged on a chromosome in a linear order with fixed, measurable distances between them, the principle that underlies genetic mapping.

Like other good model organisms, Drosophila is easy to rear in the laboratory. It has a short life cycle, lasting about two weeks, and produces many offspring. Each female can lay hundreds of eggs. These traits make it ideal for isolating mutants and carrying out many genetic crosses rapidly.

Mutants are the cornerstone of genetic analysis. To find a mutation one must be able to recognize an observable physical trait, or phenotype, such as a change in anatomical structure or behavior. At first glance, watching a tiny fruit fly landing on a rotting banana, one may be hard pressed to imagine that anyone could spot an anatomical variant, much less begin to study such a complex subject as behavior. Observed through a low-powered microscope, however, Drosophila is a sculptural masterpiece of bristles, segments, colors, and mosaic patterns. By studying Drosophila mutants, scientists have devised ways to genetically dissect the cellular bases of these phenotypes, as well as such startlingly complex behaviors as learning, memory, and even sleep.

A feature of a model organism that aids geneticists is a small genome size and a small number of chromosomes, since the less DNA there is to sort through, the easier it is to find genes. Drosophila's genome, containing about 180 million base pairs, is approximately one-twentieth the size of the human genome. There are four pairs of chromosomes: the X and Y sex chromosomes, and autosomes 2, 3, and 4. The complete nucleotide sequence of the gene-rich portion of the genome was determined in 2000. The genome is estimated to encode approximately 13,000 genes.

Drosophila molecular geneticists make wide use of transposons. These are short segments of DNA that, when injected into a cell, can insert themselves into the chromosomal DNA at random positions. Using recombinant DNA methods, a researcher can splice any gene into a transposon, which can then serve as a vector for introducing the gene into a fly.

Alternatively, transposon insertion can be used to cause mutations in genes. While much of the chromosomal DNA consists of sequences that code for non-protein elements, such as introns and "spacer" sequences between genes, a transposon may become inserted directly into a protein-coding sequence. This usually alters the amino acid sequence of the protein encoded by a gene, rendering the gene product dysfunctional. Even without knowing which gene was mutated, or where in the genome it is located, a researcher can make use of the transposon insertion as a "molecular tag" to rapidly identify the gene. Since the sequence of the transposon is known, a DNA probe can be designed to detect it (and therefore find the gene which it has mutated) by molecular hybridization methods.

An unusual phenomenon of the chromosomes in certain of Drosophila's tissues provides a powerful tool for determining the positions of individual genes. The chromosomes in the fruit fly's salivary gland cells replicate Because of their ablity to produce large amounts of offspring in a short amount of time, fruit flies were ideal specimens for early genetic experiments. several hundred times without separating from each other by mitosis and cell division. Instead, the newly replicated DNA strands line up parallel to one another to form a tight bundle, called polytene chromosomes. Polytene chromosomes are less condensed than normal metaphase chromosomes, and can be around 2 millimeters long, large enough to easily be examined in detail under a low-power microscope. When stained with certain dyes, polytene chromosomes display characteristic banding patterns along their length. Drosophila geneticists have made maps of the banding patterns and have learned to use them as landmarks to help them locate genes of interest. Polytene chromosomes make Drosophila an excellent organism for the sub-branch of genetics known as cytogenetics, which is genetic analysis through directly visualizing the chromosomes themselves.

One of the most important areas of research to come from studies on Drosophila is that of embryonic development. By analysis of mutants, developmental biologists have elucidated a complex and precise picture of how genes orchestrate the development of a fertilized egg into an adult fly. Many of the genes exercising the master control over these processes encode transcription factors, which are proteins that regulate when and where particular genes are transcribed to produce messenger RNA. The initial set of genes in the hierarchy acts in the oocyte, even before it is fertilized by a sperm. Their main function is to define the spatial polarity of the oocyte, determining which is the front and rear (posterior and anterior polarity), and which is the belly and back (dorsal and ventral polarity). These genes, in turn, activate genes that divide the embryo into segments and subsegments, which will eventually become the body segments of the adult animal. Later-acting genes, termed homeotic genes, act within each segment to define its identity, for example a wing or a leg. Remarkably, the genes and regulatory pathways involved in Drosophila development are highly conserved (that is, very similar genes and pathways are present), not only in other invertebrates, but also in mammals, including humans.