The fruit fly Drosophila melanogaster (loosely translated as “dusky syrup-lover”) was one of the first model organisms to be used in genetics. It was chosen in part because it is readily available from ripe fruit, has a short life cycle of the diploid type, and is simple to culture and cross in jars or vials containing a layer of food. Early genetic analysis showed that its inheritance mechanisms have strong similarities to those of other eukaryotes, underlining its role as a model organism. Its popularity as a model organism went into decline during the years when E. coli, yeast, and other microorganisms were being developed as molecular tools. However, Drosophila has experienced a renaissance because it lends itself so well to the study of the genetic basis of development, one of the central questions of biology. Drosophilds importance as a model for human genetics is demonstrated by the discovery that approximately 60 percent of known disease-causing genes in humans, as well as 70 percent of cancer genes, have counterparts in Drosophila.

Drosophila came into vogue as an experimental organism in the early twentieth century because of features common to most model organisms. It is small (3 mm long), simple to raise (originally, in milk bottles), quick to reproduce (only 12 days from egg to adult), and easy to obtain (just leave out some rotting fruit). It proved easy to amass a large range of interesting mutant alleles that were used to lay the ground rules of transmission genetics. Early researchers also took advantage of a feature unique to the fruit fly: polytene chromosomes. In salivary glands and certain other tissues, these “giant chromosomes” are produced by multiple rounds of DNA replication without chromosomal segregation. Each polytene chromosome displays a unique banding pattern, providing geneticists with landmarks that could be used to correlate recombination-based maps with actual chromosomes. The momentum provided by these early advances, along with the large amount of accumulated knowledge about the organism, made Drosophila an attractive genetic model.

Crosses in Drosophila can be performed quite easily. The parents may be wild or mutant stocks obtained from stock centers or as new mutant lines.

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To perform a cross, males and females are placed together in a jar, and the females lay eggs in semisolid food covering the jar’s bottom. After emergence from the pupae, offspring can be anesthetized to permit counting members of phenotypic classes and to distinguish males and females (by their different abdominal stripe patterns). However, because female progeny stay virgin for only a few hours after emergence from the pupae, they must immediately be isolated if they are to be used to make controlled crosses. Crosses designed to build specific gene combinations must be carefully planned, because crossing over does not take place in Drosophila males. Hence, in the male, linked alleles will not recombine to help create new combinations.

For obtaining new recessive mutations, special breeding programs (of which the prototype is Muller’s ClB test) provide convenient screening systems. In these tests, mutagenized flies are crossed with a stock having a balancer chromosome. Recessive mutations are eventually brought to homozygosity by inbreeding for one or two generations, starting with single F₁ flies.

Transgenesis. Building transgenic flies requires the help of a Drosophila transposon called the P element. Geneticists construct a vector that carries a transgene flanked by P-element repeats. The transgene vector is then injected into a fertilized egg along with a helper plasmid containing a transposase. The transposase allows the transgene to jump randomly into the genome in germinal cells of the embryo (see Chapter 15).

Targeted knockouts. Targeted gene knockouts can be accomplished by, first, introducing a null allele transgenically into an ectopic position and, second, inducing special enzymes that cause excision of the null allele. The excised fragment (which is linear) then finds and replaces the endogenous copy by homologous crossing over. However, functional knockouts can be produced more efficiently by RNAi.

Much of the early development of the chromosome theory of heredity was based on the results of Drosophila studies. Geneticists working with Drosophila made key advances in developing techniques for gene mapping, in understanding the origin and nature of gene mutation, and in documenting the nature and behavior of chromosomal rearrangements.

Their discoveries opened the door to other pioneering studies:

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