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Population genomics for fruitflies

Aggressive drosophila prompt study of genetic make-up.

Researchers want to sequence the genomes of a swarm of the geneticist's favourite fly. Credit: OXFORD SCIENTIFIC/PHOTOLIBRARY.COM

Starve a fruitfly for a couple of hours, and it gets a little cranky. Pop it into a fruit-fly-sized ring, add seven other starving flies and just one piece of food, and you'll have a riot. “They stand up on their little hind legs and tussle,” says geneticist Trudy Mackay at North Carolina State University in Raleigh. “And then there's the wing slap,” adds her collaborator, Robert Anholt.

Researchers in Mackay's lab quantify aggressive behaviour by counting how often each fruitfly wrestles, slaps, or chases its competitors. They have uncovered a wide range of responses, even among members of the same species. One fly had 100 aggressive inter-actions in two minutes; others had as few as three. “Those are the pacifists,” says Mackay. “They sit there and share the food.” Anholt sums up the data succinctly: “There's enormous variation — from flies that are real wimps to flies that really beat the shit out of each other.”

It's that sort of variation that has inspired Mackay and her colleagues to propose an ambitious new drosophila genomics project: sequencing the genomes of 192 flies. The aim is to use this information to understand the genetic changes underlying the variation in behaviour and appearance in natural populations. By breaking free from lab strains that have spent decades living in vials on lumps of smelly, sterilized lab food, researchers hope to get a better glimpse of the evolutionary forces at work in fly populations. “The history of a population can leave a kind of footprint on the genome,” says fruit-fly researcher Esteban Hasson of the University of Buenos Aires. “Perhaps we will be able to map the mechanisms that shaped the variation found in these flies.”

The flies are all members of the same species — the classic genetic model organism Drosophila melanogaster — but, unlike some lab populations, they have been kept in the lab for only five years — since their ancestors were trapped at a farmers' market in Raleigh. They have been inbred for 20 generations in the lab to produce a collection of 'pure-bred' flies that are amenable to genetic analysis. Flies obtained from the wild have been used to study natural variation before, but the work can be arduous. Having full genome sequences promises to dramatically speed up the process, says Mackay.

This project, which was recently approved by the US National Human Genome Research Institute in Bethesda, Maryland, is expected to cost around US$4 million and to take about two years. Although similar projects are under way in other model organisms (see 'What's the magic number?'), most of those are smaller and will sequence only targeted regions of the genome. Even when a full genome is the goal, it is typically only a 'draft' sequence that contains a relatively high frequency of gaps and errors.

The drosophila project, in contrast, aims to produce high-quality sequence using two high-throughput sequencing methods with complementary strengths. The machines produced by Illumina of San Diego, California, are particularly good at detecting single base differences in the DNA sequence, whereas the sequencers from 454 Life Sciences of Branford, Connecticut, are better at finding regions in which large stretches of DNA have been inserted or deleted. “I'm after as much sequence as I can get, in a very greedy way,” says Stephen Richards of Baylor College of Medicine in Houston, Texas, who is an investigator on the drosophila project.

This approach will provide a useful testing ground, says population geneticist Philip Awadalla of the University of Montreal in Canada. Awadalla usually studies genetics in humans and in the malaria parasite, but says the analytical tools developed in the drosophila project could be useful for his work. Awadalla also plans to analyse the drosophila sequences once they become available. The small genome and the ease with which different strains of D. melanogaster can be characterized provide clear advantages over humans or other insects, he says.

Drosophila researchers are renowned for devising creative ways of studying their beloved flies. Researchers are already lining up to study Mackay's wild isolates, with plans to study learning and memory, wing morphology, body size, social behaviour, circadian rhythm and responses to different odours and drugs. Hasson will try to determine why some flies like to lay their eggs in grapes whereas others prefer oranges, and Anholt will test responses to alcohol using his 'inebriometer', a device that measures how quickly flies become woozy from ethanol fumes.

Richards says that similar projects in other insects, such as mosquitoes or honeybees, could be on the horizon. “The cost of sequencing is coming down so quickly; in the future it'll just be a normal grant proposal to do 500 insects,” he says.

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Ledford, H. Population genomics for fruitflies. Nature 453, 1154–1155 (2008). https://doi.org/10.1038/4531154a

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