Spots Before Your Eyes - Making Sense Of The Fly Genome
Wander in a south-westerly direction out of Cambridge city centre, down meandering streets and through fragrant college gardens, and you will come across an elegant wooden bridge. Local legend has it that the Mathematical Bridge at Queens' College was constructed by Isaac Newton in such a way that it is held aloft by the power of mathematics alone. The legend continues that inquisitive students once took it apart to see how it worked and - like all the king's horses and all the king's men - couldn't put it together without the aid of screws and nails. Less than half a mile east of the Mathematical Bridge, not far from where James Watson and Francis Crick unravelled the similarly exquisite structure of DNA, geneticists are likewise puzzling over the genome of the fruit fly, Drosophila melanogaster.
This remarkable insect, named after its penchant for rotting fruit, achieves more in its forty day lifespan than your average human does in seventy years. It can fly, coordinate six legs simultaneously and produce thousands of offspring, all in a body of half a centimetre in length. It has long been a tool of the biologist and offers insights into the principles of basic biology and the mechanisms of human diseases such as Parkinson's, Huntingdon's and cancer.
The genetic recipe for the fruit fly was first published in March 2000, consisting of around 120 billion individual letters and estimated to contain approximately 13,000 genes. Unfortunately, relatively speaking, that was the easy part. The challenge now is to understand how the actions of different genes combine to create a wing rather than a leg, produce Mr Fly instead of Mrs Fly, or allow flies to break down alcohol and avoid that 'morning after feeling'. In other words, how to put the bridge back together again.
Imagine messengers carrying blueprints from head office to the factory floor. It would be easier for an industrial spy to intercept many messages in one go rather than to reverse engineer many finished products. In a similar vein, attach the DNA sequences for many known genes to a glass slide, and we have what is known as a microarray or gene chip. To compare the genes being used in two different flies - for example, male versus female - we extract the messenger molecules from each fly and label them with a different coloured dye, red for males and green for females.
Due to the basic chemical properties of DNA, the messenger molecule for a particular gene will bind to the DNA sequence for that gene on the microarray. The end result is an image, reminiscent of a tiny Twister mat, with spots lit up in varying shades of traffic light colours. Measuring the colour of each spot gives us a relative measure of expression for each gene. In this case, bright red indicates a gene is being strongly used in males, bright green means it is strongly used in females and black means there is no difference between the two sexes.
In the FlyChip lab, we currently produce arrays containing approximately a third of all fruit fly genes and my aim is to extract biological knowledge from the mass of resulting data. Microarray experiments can be repeated for many flies in many different conditions. For example, sex specific genes can identified by looking for consistent results across several strains of fruit fly.
Of course, the legend of the Mathematical Bridge is just that - pure fiction. Isaac Newton died in 1727, twenty two years before the bridge was built by James Essex using screws to fasten the beams of wood together. At FlyChip, we are confident that microarrays will prove useful in uncovering the nuts and bolts of biology and that the story of the fly genome will come to a more successful conclusion.