Oddballs in Every Way

WHAT AUDREY GASCH SAW IN HER PETRI DISH MADE NO SENSE. The assistant professor of genetics was just getting a research program launched on the genetic mechanisms of yeast, the fungi that naturally convert sugars into alcohols like wine and beer. But she was having trouble with a lab-bred strain of Saccharomyces ceravisiae, a type of yeast studied by scientists for nearly a century. It just couldn’t hold its liquor. After producing relatively small amounts of alcohol, the cells shut down, too stressed by the alcohol around them to go on.

“We thought, ‘Hold on, yeast naturally produce alcohol, so they should be able to handle this kind of environment,’ ” says Gasch BS’94. “Either what we thought about nature was wrong, or something about this lab strain was wrong.”

To figure out which, Gasch began studying strains of yeast collected from all over the planet, including yeasts found growing in an Italian winery, a Trinidadian rum distillery and even a patch of Wisconsin soil. In the lab, she subjected the wild strains to tests to see how much alcohol they could tolerate. Her conclusion: Strains of yeast raised in labs are wimps.

“They’re really oddballs in just about every way that we look,” she says. “So what’s happened is that lab scientists have inadvertently been selecting a strain that is very friendly for genetic experiments, but not very representative of what’s in nature. They’ve evolved to live in the lab.”

Scientists have long known that animals that they raise in labs are a more domesticated bunch. A white-haired lab mouse will often sit patiently in a lab technician’s palm, a model of pink-eyed civility. “If you ever catch a mouse in your house, you know that’s not how they behave,” says Bret Payseur, an assistant professor of genetics who studies both wild and lab mice in his lab. To some extent, all model organisms—from mice to fruit flies to tomatoes and corn—have been changed by our studying them. Over generations, they’ve grown accustomed to the perks and hardships of life in the lab.

Some researchers are beginning to explore just how different lab species are from their wild relatives—and what that may mean for the research we perform on them. Beth Dumont, a graduate student in Payseur’s lab, has found that DNA recombination rates can vary widely among mice that live in the wild, which she thinks reflects divergent patterns in their evolution.

“Something really interesting is going on with regard to recombination in house mice,” says Dumont. “In subspecies that are about as diverged from each other as humans are from chimpanzees, recombination rates vary by about 30 percent.” That suggests that far greater genetic diversity may have evolved within species than one might guess from studying their lab counterparts.

That doesn’t mean that studies on lab mice aren’t useful. “A big reason why we can study wild mice is that we know so much about them from lab studies,” says Payseur. “If you want to understand natural selection, that’s best done in a natural environment. But there are things you can do in a lab that you can’t do in the wild. What we try to do is use them in combination.”

Ultimately, Gasch had the same idea. Her team is now using wild yeast as a platform for engineering lab strains that can better stand up to the pressures of a hard life. Toughening up yeast could aid the industrial production of ethanol, which requires fungi to perform in hot, caustic surroundings.

“We’re finding that it makes sense to look to nature first,” says Gasch. “There’s a lot of genetic diversity out there that isn’t reflected by these happy little lab strains.”