Fruit flies in the laboratory

Although generally considered a pest by farmers because they lay their eggs in ripening fruit, in the laboratory the fruit fly has proved to be one of the most useful tools for studying a whole range of biological processes, from ecology to alcoholism.

There are many qualities of the fly that make it such a desirable organism to study.

There are many qualities of the fly that make it such a desirable organism to study. It has a short life cycle, simple reproduction and is relative inexpensive to maintain. However, the most useful characteristic of flies, particularly to human genetics research, is the close similarity between the genes of flies and humans.

History of the fly

The story of the fruit fly as a model organism begins in the early years of the 1900s. At this time Gregor Mendel’s work on inheritance had been rediscovered, but scientists still had a very limited understanding about how inheritance worked.

American embryologist Thomas Hunt Morgan is considered the founding father of Drosophila research, and arguably the father of genetics in the USA. Thomas started working with Drosophila in 1908. He was most interested in studying its embryology, the science of the development from fertilisation to formation of an embryo.

Speculation that chromosomes might in some way be linked to an organism’s characteristics spurred Thomas’ interest in inheritance. At that time he was very sceptical of Mendel’s laws of inheritance and did not agree with Darwin’s ideas about natural selection. However, he was about to make a finding that would change his opinions completely.

Chromosomal theory of inheritance

After a frustrating and fruitless two-year search for Drosophila with different characteristics, white-eyed flies suddenly appeared among Thomas Morgan’s normal, red-eyed flies. To find out more about these white-eyed flies, Thomas carried out crosses between them and the red-eyed flies. Through these early experiments he found that all of the white-eyed flies being produced were males, there were no white-eyed females at all.

Inheritance of the white-eye trait might have a basis in the chromosomes, more specifically, the sex chromosomes.

After further crosses Thomas observed that the female flies only showed the white-eyed trait if they inherited two copies of the mutant genes, but males only needed one copy of the mutant gene to have white eyes. This suggested to him that inheritance of the white-eye trait might have a basis in the chromosomes, more specifically the sex chromosomes. At that time, little was known about the sex chromosomes, although it was thought that one of the Drosophila’s four chromosome pairs was likely to be involved in sex determination.

Thomas continued his work looking at a number of different traits in the Drosophila and in 1915 he published his theory Mechanism of Mendelian Heredity, acknowledging that he agreed with Mendel’s concept of dominant and recessive traits. In his work he introduced the concept of genes carrying hereditary information and explained the discovery that certain characteristics were linked to sex. He also revealed that different combinations of traits arise from changes occurring in the chromosomes during reproduction.

Thomas Morgan received the Nobel Prize for Medicine in 1933.

In 1933 Thomas Morgan received the Nobel Prize for Medicine for his work in establishing the chromosomal theory of inheritance. His work with the Drosophila heralded a flurry of fundamental discoveries about inheritance.

Body structure and development

Between the 1940s and early 1970s, Drosophila research continued to be productive. Different mutants were made in which the function of one or some genes were altered or removed completely. New techniques were also developed to make it easier to handle flies in the laboratory. Important foundations were laid during this time, yet the relationship between heredity and development went unresolved. There was a long period where it wasn’t clear whether the fly was going to yield anything of true significance.

In the late 1970s and 1980s Drosophila research hit top gear.

Then, in the late 1970s and 1980s, genetics, embryology and molecular biology came together in a glorious union, and Drosophila research hit top gear. The new science of molecular biology brought with it the ability to manipulate DNA, and researchers could finally get at the genes behind fly mutants. Particularly influential were mutations studied by Ed Lewis, which caused strange transformations of the body structure.

The ‘bithorax complex’ (see illustration below) is a group of genes, located on chromosome 3, believed to control the separation of the middle (abdominal) and rear segments of the fly’s body. Mutations in the genes in the bithorax complex lead to flies with two sets of wings or legs on abdominal segments.

The ‘antennapedia’ complex (see illustration below) is a group of genes responsible for formation and differentiation of the head and front (thoracic) segments of the fly’s body. Mutations found in these genes resulted in flies with legs where antennae should be. The strangeness of these changes was in fact a clue to the crucial role of the genes in the bithorax and antennapedia complexes, for they turned out to be groups of master control genes that programme the final body structure of the fly.

Around this time, Christiane Nüsslein-Volhard and Eric Wieschaus began working together on the fruit fly in a small laboratory at the European Molecular Biology Laboratory in Heidelberg, Germany. They examined thousands of mutated embryos with disrupted development and, as a result, identified a series of new genes that drive the early development and the formation of body parts of the organism.

These new genes included genes whose product is transferred from mother to embryo (maternal-effect genes) and genes which are expressed by the embryo itself (zygotic ‘segmentation’ genes). The maternal-effect genes are involved in specifying major body axes (anterior-posterior and dorsal-ventral), while the segmentation genes (‘gap’ genes, ‘pair-rule’ genes and ‘segment polarity’ genes) define the different segments along the anteroposterior axis of the developing embryo.

It is thought that more than 75 per cent of genes involved in human disease have counterparts in the fly.

Since 1999, the genome sequence of Drosophila has been available, and researchers are using high-throughput DNA sequencing technologies to look at patterns of gene and protein expression. From comparisons with the human genome, it is thought that more than 75 per cent of genes involved in human disease have counterparts in the fly.

Nearly a century on from Drosophila’s entrance on the world stage of biological research, this tiny fly has become one of the most well understood organisms there is.