Beer: Yeast DNA study reveals the natural history of lager

Scientists use DNA to figure out a lot of useful stuff: whether a drug will work to fight a certain form of cancer, who committed a crime, the ancient history of a fragment of fossilized bone.

Now a team led by biologists at the University of Wisconsin-Madison are putting genetic analysis to work to get to the bottom of a different sort of compelling question: the evolution of lager beer.

Sequencing the DNA of a recently discovered type of yeast believed to be key to brewing lagers, University of Wisconsin-Madison evolutionary geneticist Chris Todd Hittinger and colleagues were able to identify genetic signatures of domestication in modern lager yeast. They were also able to resolve a question about the two major lager yeast lineages, Frohberg and Saaz, discovering that the two had separate origins, not a single precursor, as some groups had hypothesized.

The researchers' study was published Tuesday in the journal Molecular Biology and Evolution

Hittinger and colleagues have been circling the globe for years chasing the origins of lager, a long-standing mystery. For centuries, people had brewed ale using the same type of yeast they used to make wine and to bake bread: a species known as Saccharomyces cerevisiae. Eventually, around the 15th century,  Bavarian monks found a way to make lager in cooler temperatures, using a hybridized yeast. But no one was sure what other yeast strain had mixed with the ale yeast to make the lager hybrid.

In 2011, Hittinger's team figured it out: a species called Saccharomyces eubayanus, discovered, oddly enough, on the sides of beech trees in chilly Patagonia, in South America. ("We knew it had to be out there somewhere," Hittinger said at the time.)

Preliminary genetic analysis of S. eubayanus showed it was a close match to the non-S. cerevisiae portions of lager yeast ,but the scientists didn't know much more about it. In years since, Hittinger's lab and other groups have continued searching for S. eubayanus, finding plenty of it in the Southern Hemisphere but only a few samples in the Northern Hemisphere, including strains in Wisconsin and in China.

It still hasn't ever been sighted in Europe, and scientists don't really know how it might have made its way there and made its way into lager yeast, Hittinger said.

"The biogeography is still very much a mystery," he said.

The new research, a high-quality catalog of the DNA in S. eubayanus, didn't provide an answer either.  But it helped shed light on other questions the scientists had about lager yeast.  For instance, Hittinger said, the scientists wanted to see whether lager yeast displayed typical genetic signs of domestication, such as the increased rates of evolution that had been seen in other types of domesticated organisms, such as plants and animals. Comparing lager yeast DNA with S. eubayanus DNA showed that certain genes had in fact evolved more rapidly in the domesticated yeast -- some of the genes were involved in carbon metabolism, which would have been implicated in cultivating yeast and and brewing beer.

The genome analysis also allowed the team to pin down the origins of the Saaz and Frohberg lager yeast lineages, concluding that they first emerged from different S. cerevisiae sources, both of which hybridized separately with similar strains of S. eubayanus. The Saaz strain has largely fallen out of favor with beer makers, Hittinger said, and this new evidence shows that there is a genetic basis for those properties that make it less desirable.

Conversely, he wondered what other yeast strains, lurking undetected in nature, might harbor genes that could make beers better.

"There's a lot of diversity that's been left on the table," he said of the strains used in industrial brewing settings today. "It raises the question: In the entire population, are there additional variants that might be useful? Is it an accident of history what gets hybridized?"

Hittinger said his lab would continue studying beer yeast DNA and searching for S. eubayanus specimens from the Northern Hemisphere to better understand the "biogeographic diversity that somehow gave rise to lager."

He's also planning to apply the research to creating biofuels. Just as S. eubayanus genes helped ale yeast make beer in cold conditions they otherwise couldn't tolerate, a different set of borrowed genes might be able to help yeast withstand toxins involved in making biofuels.

"It's the same idea," Hittinger said.

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