A model relationship
University of Arizona biologist Noah Whiteman wasn’t looking for treasure in the dog park where he regularly exercised his hyper Hungarian sporting dog, Tilla, during his postdoc days at Harvard between August 2006 and January 2010. But that’s what he found when he spotted mustard-yellow flowers with bumpy leaves while following Tilla down an embankment. A naturalist at heart, Whiteman let Tilla off her leash and bent down to take a closer look at the plants. “On the lowest leaf I saw these weird mines,” Whiteman recounts, “I had bags with me for picking up dog shit and I put a ton of these leaves in them.”
Back in the lab he classified the plants as relatives of Arabidopsis, and from the mines he picked out insect larvae burrowed into the leaves. After the larvae metamorphosed, he identified the adult flies—an arduous process that included dissecting their microscopic genitalia. They were scaptomyzan flies, which belong to family Drosophilidae, best known for including the geneticists’ go-to model, Drosophila melanogaster. Unlike most of their family mates, scaptomyzans eat living plants, instead of microbes on rotting tissue. There in the urban wilds, Whiteman had found two model organisms (or at least close kin) living in unison. “Tilla’s been with me for all my great finds,” he says.
For decades, ecologists have studied coevolution, symbiosis, and parasitism by conducting field observations and experiments. In labs, molecular biologists have genetically manipulated solitary model organisms to uncover the genes underlying their physiology and behavior. But Whiteman is part of a new hybrid breed of researchers called ecological genomicists who want to know how the genes of one organism interact with the genes of another. In the dog park that spring, Whiteman stumbled on a scientific treasure—an eminently tractable genomic ecosystem.
Arabidopsis was the first plant to have its genome sequenced, and 12 Drosophila species, which geneticists have studied for a century, now have sequenced genomes. With this ecosystem model, Whiteman can use modern genomic approaches to tease out the molecular basis for the arms race between hosts and parasites.
Thomas Mitchell-Olds, an ecological geneticist at Duke University, says that Whiteman’s discovery typifies the approach necessary to push the field of ecological genomics forward. “People need to get away from air conditioning and iPods and get their knees dirty in order to answer scientific questions,” he says.
“The generation of scientists I find myself in is different than the one before,” says Whiteman, “and to some extent it’s ground that’s never been walked on.”
Whiteman brought the ecosystem out of the dog park and into the lab. He sequenced whole scaptomyzan transcriptomes to profile gene expression at each stage of the fly’s development and ordered Arabidopsis knockouts lacking the genes that make predator-deterring mustard oils. Scaptomyzans reared on the knockout plants hardly expressed genes that aligned with detoxification proteins in D. melanogaster, suggesting that the flies strongly turn on these genes when plant toxins abound. Whiteman also found that injecting Arabidopsis with chitin (a glucose polymer derived from insect exoskeletons), fungal cell walls, or worm eggs, drove the plants to activate genes that break down chitin as well as genes for other defense compounds. In response, the expression level of fly detoxification genes soared.
In his University of Arizona lab, Whiteman is now pushing his system further by using genetic tools designed for the study of D. melanogaster. By inserting genes encoding detoxification enzymes into D. melanogaster, he’ll try to turn this microbe-munching lab fly into a plant eater. If that doesn’t do it, perhaps inserting leaf-mining genes will change the fly’s lifestyle. “A main question is: How is living on a plant that’s trying to kill you different from living on a plant that’s rotting,” he says. “And what are the consequences genomically for the fly?” He’s preparing to have the Scaptomyza flava genome sequenced next year at Baylor College of Medicine in Houston, Texas.
“Microarray studies just give you correlations,” explains Fred Ausubel, a molecular biologist at Harvard Medical School. “What you really want to do is have a genome and the tools to manipulate genes to see how mutations affect interactions.”
As more genomes are sequenced each year, the chances of stumbling on another natural genetic model system improve. A dog, however, just might help chase it from the bush.