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Bubble, bubble, toil and trouble – yeast dynasties give up their secrets

yeasty brew

Apologies to Shakespeare for the misquote (I've just learned to my surprise that it's actually "Double, double, toil and trouble"), but it's a too-perfect lead-in to geneticist Gavin Sherlock's recent study on yeast population dynamics for me to be bothered by facts.

Sherlock, PhD, and his colleagues devised a way to label and track the fate of individual yeast cells and their progeny in a population using heritable DNA "barcodes" inserted into their genomes. In this way, they could track the rise and fall of dynasties as the yeast battled for ever more scarce resources (in this case, the sugar glucose), much like what happens in the gentle bubbling of a sourdough starter or a new batch of beer.

Their research was published today in Nature.

From our release:

Dividing yeast naturally accumulate mutations as they repeatedly copy their DNA. Some of these mutations may allow cells to gobble up the sugar in the broth more quickly than others, or perhaps give them an extra push to squeeze in just one more cell division than their competitors.

Sherlock and his colleagues found that about one percent of all randomly acquired mutations conferred a fitness benefit that allowed the progeny of one cell to increase in numbers more rapidly than their peers. They also learned that the growth of the population is driven at first by many mutations of modest benefit. Later generations see the rise of the big guns - a few mutations that give carriers a substantial advantage.

This type of clonal evolution mirrors how a bacterium or virus spreads through the human body, or how a cancer cell develops mutations that allow it to evade treatment. It is also somewhat similar to a problem that kept some snooty 19th century English scientists up at night, worried that aristocratic surnames would die out because rich and socially successful families were having fewer children than the working poor. As a result, these scientists developed what's known as the "science of branching theory." They described the research in a paper in 1875 called "On the probability of extinction of families," and Sherlock and his colleagues used some of the mathematical principles described in the paper to conduct their analysis.

Sherlock's research is always fun to write about. In 2008, he and his colleagues published research describing how the present-day lager yeast strain originated from a Bavarian decree to brew beer only during the colder months, when the resulting brew was more tasty. And in 2012 they showed that wine-making yeast in use today is the result of a frenzy of indiscriminate coupling in wine vats during the past several centuries. (Giving me the opportunity to write what I believe are a couple of my best opening lines: "It all started with some unhappy Bavarians," and "Humans aren’t the only species that like to get busy with a glass of bubbly.")

Joking aside, this current research has only been possible in the past couple of years, due to advances in sequencing technology that allowed Sherlock and his colleagues to detect the presence of yeast families whose members make up only about one in every 100,000 cells in the population. As we describe in our release:

Monitoring cells present only in very small numbers allowed the researchers to see the full spectrum of growth and extinction rates in the population."Just because a family goes extinct doesn't mean it couldn't have been important," said Sherlock. "Even those with mildly beneficial mutations play a role, perhaps by preventing families with even less beneficial mutations from increasing in size."

Previously: Get sloshed, have sex? Wine-making has promoted a frenzy of indiscriminate mating in baker's yeast, according to Stanford researchers
Photo by Jim Champion

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