Why the fly?

The most common question I’m asked when I tell people that I work in fruit fly research, is why the fly? Why do so many researchers dedicate their time to studying flies?

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The fruit fly – Drosophila melanogaster  (‘Drosophila‘ by Katja Schulz is licensed under CC BY 2.0)

Drosophila melanogaster (more commonly known as the fruit fly) has been a prominent figure in a wide range of biological research for over 100 years. Thousands of researchers in labs across the world currently study the fruit fly, and work based upon them has led to the awarding of multiple Nobel Prizes.

The breadth of research that uses the fly is huge: evolution, ageing, genetics, disease, neuroscience etc. etc.

So the question remains, what is it about flies that makes them so useful?

The Fruit Fly

Most people probably know fruit flies as those tiny (and rather annoying) animals that hang around our fruit bowls in the summer. I find it rather entertaining that most of the top hits on entering ‘fruit fly’ into google are pest control sites detailing the top ways to eradicate them from your home.

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The life cycle of the fruit fly             (‘Drosophila melanogaster Life Cycle‘ by Image Editor is licensed under CC BY 2.0)

Yet, working with the fruit fly has a number of practical advantages that make it ideal for research. For one, they’re tiny (at around 3mm in length) and have a rapid life cycle, taking around 10 days to develop from an egg to an adult. Many experiments rely on being able to breed organisms of different genotypes (the complete set of genes of that organism) together and look at the offspring – this can be done rapidly in the fly as it breeds so quickly and in such great numbers. A female fruit fly will lay between 750 and 1500 eggs in her lifetime!

As flies are so small, it is possible to keep large numbers of them in even a very small lab. They will happily breed in small vials, and can be fed inexpensive foods. In a nutshell, they’re easy and cheap to keep and allow you to do experiments fast!

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Left – fruit fly next to a 20p piece for scale; Right – fruit flies and larvae/pupae kept in vials (the food is the brown layer at the bottom) (Left – ‘Drosophila melanogaster and a 20p Piece‘ by Mark Longair is licensed under CC BY-SA 2.0; Right – ‘aditl-109‘ by Robert Cudmore is licensed under CC BY-SA 2.0)

Also, fruit flies have the advantage of allowing us to do experiments that would be impossible to do in many other animals (e.g. mice, primates…) for ethical reasons.

An Illustrious History

For all the practical reasons to use Drosophila in research, the major reason they are so widely used today is historical. The success of early studies using fruit flies attracted many others to using them in their research.

Thomas H. Morgan

To give some examples, the work of Thomas H. Morgan and coworkers is some of the most famous. It was the success of their work that first brought the fruit fly to the wider biological community.

Morgan began his work on the fruit fly in a time when Gregor Mendel’s work on inheritance had recently been rediscovered. Mendel proposed laws for how different traits are inherited from one generation to the next, but gave no indication as to what the physical nature of these inherited factors might be. Many at the time were therefore working to try and tie down the physical nature of the gene – where and how was this information being inherited in the cell?

Morgan began conducting experiments with fruit flies, breeding them in large numbers in the ‘Fly Room’ at Columbia University. In 1910, he observed an abnormal fly with white eyes, in contrast to the usual red. After a series of breeding experiments, he realised that this trait (white eyes) was being inherited in a sex-linked way. He noticed that its inheritance matched with the inheritance of the X chromosome, providing the first correlation between a specific trait and a specific chromosome.

L0060920 The physical basis of heredity
Diagrams of a mating scheme between white and red eyed flies from The physical basis of heredity by Thomas Hunt Morgan (‘L0060920‘ by Wellcome Images is licensed under CC BY 4.0)

Morgan, along with others in his lab (most notably A. H. Sturtevant, C. B. Bridges and H. J. Muller), made valuable contributions to the ‘chromosomal theory’ of inheritance, i.e. that chromosomes carry genes that determine specific traits. The work of this lab was incredibly important to our modern understanding of genetics and inheritance. [Morgan was awarded the Nobel Prize in Physiology or Medicine in 1933; with Muller later receiving it in 1946]

Lewis, Nϋsslein-Volhard, Wieschaus

Another example of important work conducted using the fruit fly is that of Lewis, Nϋsslein-Volhard and Wieschaus – this work resulted in them being awarded a Nobel Prize in 1995.

A key question in biology is how do genes determine the body plan of an organism? How do we go from genes to the actual form of the organism?

Nϋsslein-Volhard and Wieschaus wanted to discover the genes involved in turning a fly egg into an embryo. In order to do this they conducted a large ‘genetic screen’: this involved feeding mutagenic substances to flies to cause damage to their various genes. After, they looked at the larvae produced to see the effects of these mutations on the process of development from the egg. This identified a wide range of genes that are important in this process.

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Image of a Drosophila larva about 22 hours old. The vertical bands are patches of ‘denticles’ (small spiny projections) that help the larva to grip onto the surface and move itself along. (‘DrosophilaKutikula‘ via Wikimedia Commons is licensed under CC BY-SA 3.0)

Edward B. Lewis also worked on the fruit fly, focusing on the ‘homeotic genes’. He demonstrated that these were present as a complex with genes nearest the start controlling the development of fly segments closest to the head, and genes towards the end controlling segments furthest from the head. The principles he established have since been found to hold true for a wide range of organisms, including mammals.

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Left – sketch of the effect of mutating the Ultrabithorax gene (a homeotic gene) in the fruit fly. Another thorax forms bearing a second pair of wings. Right – picture of the effect of mutating the Antennapedia gene (another homeotic gene). This causes legs to form in place of the usual antennae. (Left – ‘Drosophile normale et bithorax‘ by Rachgo20 via Wikimedia Commons is licensed under CC BY-SA 4.0; Right – ‘Mutation Antennapedia’ by toony via Wikimedia Commons is licensed under CC BY-SA 3.0)

Both of these sets of work identified genes that control the process of development from an egg to an adult organism. This work on the fly was a leap forward in our understanding of how genes determine the form of an organism.

A growing community

These are just a few examples of important discoveries that have been made using the fruit fly. As a result of the ease of doing research with Drosophila and also the success of studies using them, the community of researchers that work on them has grown massively.

As more researchers work on the fly, more resources and techniques become available that make it great for research. E.g. the genome of Drosophila has been sequenced and there are large databases of genes and other experimental results on websites such as FlyBase.

Also, there’s a wide range of genetic tools that allow us to precisely manipulate the genes of the fly, in a way that’s not possible in many other animals. Various stock centres across the world also maintain different strains of flies, providing a repository of useful genotypes for research. This allows labs to order and exchange flies, allowing them to research new areas.

Conservation

So flies are a great system for biological research, but are the principles discovered in flies relevant to other organisms?

Luckily for us, the answer is often yes. Many genes that are present in flies have similar forms in many organisms, including humans. For example, out of the genes in humans that have been linked to disease, it is estimated that as many as 75% are conserved to some extent in the fruit fly.

As an example, take the ‘hedgehog’ gene. This gene was discovered in flies in the Nϋsslein-Volhard and Wieschaus screen that I mentioned above. Mutations in this gene resulted in embryos that were covered with denticles (which are small spiny projections) hence the name ‘hedgehog’. This gene has a key role in controlling what types of cell form in different areas of the embryo. Similar genes have since been found in humans, notably ‘sonic hedgehog’ (an example of the wonderful weirdness of gene names) that also serves a role in development.

Finally, Drosophila lies in a sweet spot for complexity – it’s a simpler system than many animals (e.g. having fewer genes (and only 4 chromosomes)) which makes it easier to gain a foothold on understanding many biological processes. For many, this can then be generalised and studied

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A fruit fly brain with some neurons labelled with GFP (green). The fly brain is made up of about 100,000 neurons! (‘Drosophila multi-photon imaging’ by ZEISS Microscopy is licensed under CC BY-NC-ND 2.0)

in organsims where these processes are more complex. Still, Drosophila is complex enough that it has many fascinating properties to study. To take some examples from Neuroscience, Drosophila have relatively small brains (made up of about 100,000 nerve cells (neurons)) which makes them amenable to study, but they still show complex behaviours such as courtship, sleep and learning. This makes them an ideal system to start to understand the basis of such behaviours in the brain.

 


The fruit fly – Drosophila melanogaster – has been used to great effect for over 100 years. The success of early experiments using the fly, coupled with the ease with which it can be used has led to a large community of Drosophila researchers in the modern day. It continues to be used to study an astounding array of different subjects – and we won’t be done with the fruit fly for many years yet! There’s still so much that this tiny fly can tell us about biology.

References / suggestions for further reading

droso4schools – https://droso4schools.wordpress.com/why-fly/ – excellent website with information on the fruit fly, the videos at the bottom of this page are really nice introductions

modENCODE – http://modencode.sciencemag.org/drosophila/introduction – an introduction to the use of fruit flies in research

FlyBase – http://flybase.org/ – An online database of Drosophila genes and genomes

Scitable by Nature Education – https://www.nature.com/scitable/topicpage/thomas-hunt-morgan-and-sex-linkage-452 – a great overview of Morgan’s work on the white eyed flies

nobelprize.org – http://www.nobelprize.org/nobel_prizes/medicine/laureates/1933/ and http://www.nobelprize.org/nobel_prizes/medicine/laureates/1995/ – overviews of the work of Morgan, as well as Lewis, Nϋsslein-Volhard, Wieschaus that led to them being award Nobel Prizes

Khan Academy – https://www.khanacademy.org/science/biology/developmental-biology/signaling-and-transcription-factors-in-development/a/homeotic-genes – A nice overview of homeotic genes in the fruit fly

Rubin, G. M. & Lewis, E. B. T HE DROSOPHILA GENOME A Brief History of Drosophila’s Contributions to Genome Research. 287, 2216–2218 (2000) DOI: 10.1126/science.287.5461.2216 – a brief overview of Drosophila’s use in research

Letsou, A., Bohmann, D. & Morgan, T. H. Small Flies — Big Discoveries : Nearly a Century of Drosophila Genetics and Development DEVELOPMENTAL. 526–528 (2005). DOI: 10.1002/dvdy.20307 – another nice overview of the history of fruit flies in research

Wieschaus, E. & Christiane, N. The Heidelberg Screen for Pattern Mutants of Drosophila : A Personal Account. (2016). DOI: 10.1146/annurev-cellbio-113015-023138 – review of the screen performed by Nϋsslein-Volhard and Wieschaus (written by themselves!)

Johnston, D. S. The art and design of genetic screens: Drosophila Melanogaster (2002) DOI: 10.1038/nrg751 – a nice overview of the use of Drosophila for genetic screens

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