Discovery has implications for beer history – and medicine

It doesn’t take a genome sequencer to figure out that lager brewing began in Bavaria in the 15th century. But the origin of the yeast that makes lager beer remained a mystery – until now.

Molecular geneticists knew that lager yeast is a hybrid created by the fusion of an ale yeast and a fairly distant relative – about as distant from ale yeast as human is from chicken. The species that joined with ale yeast was assumed to provide the ability to ferment at cold temperatures, the hallmark of lager production.

But no one could find it. Then a team of scientists on three continents went to work.

“It was fun trying to track down the mystery yeast,” says Mark Johnston, Ph.D., chair of the Department of Biochemistry and Molecular Genetics at the University of Colorado School of Medicine. “But it also was important.”

Johnston worked with scientists from the New University of Lisbon in Portugal and the Institute for Biodiversity and Environment Research in Bariloche, Argentina. Their findings were published this week in the Proceedings of the National Academy of Sciences.

“People have been hunting for this thing for decades,” says Chris Todd Hittinger, a member of the Colorado team, now a professor at the University of Wisconsin-Madison.

The researchers didn’t set out to find where lager beer came from. But the secret ingredient in the beer popped up in a broader search for new yeasts.

The detective work began in Europe, which seemed logical, but no yeasts there fit the profile. They found what turned out to be the missing piece an ocean away in the Southern beech woodlands of Patagonia.

The new yeast was hustled off to the University of Colorado School of Medicine where Hittinger and Jim Dover in Johnston’s lab sequenced its genome.

They named it Saccharomyces eubayanus. It likes the cold, and its DNA sequence looks like that of the unidentified component of the lager yeast genome.

The Colorado team also identified genetic mutations in the lager yeast hybrid distinctive from the genome of the wild lager yeast. Those changes – which likely took place in a brewing environment where evolution is amped up by the great abundance of yeast – accumulated since those first immigrant yeasts melded with their ale cousins 500 years ago, and refined the lager yeast’s ability to metabolize sugar and malt and to produce sulfites, transforming an organism that evolved on beech trees into a beer-making machine.

How did yeast get from South America to the caves and monasteries of Bavaria where lager beer was born? They don’t know. But lager beer brewing began at about the same time as the rise of trans-Atlantic trade, so the yeast may have hitched a ride on a sailing ship, perhaps on a piece of wood or in the stomach of a fruit fly.

That cold-loving hybrid then evolved into the modern lager yeasts that are used today in breweries throughout the world, acquiring several genetic changes that altered their sugar and sulfur metabolism.

“We pursued this mostly just because we want to figure out how things work and why things are the way they are,” Johnston says. “But there's more to it. What we’ve learned about relatively simple organisms like yeast has helped scientists understand the human genome and how variations in the DNA sequence lead to disease. So, remarkably, our experience working out DNA sequences differences in the genomes of brewing yeasts could help us tackle the more difficult challenge of personalized medicine – using knowledge of an individual’s human genome sequences to improve health care.”