Prions point to a new style of evolution

THE rogue proteins behind variant CJD, the human form of mad cow disease, have revealed their benign side. Prions, it seems, lie at the heart of a newly discovered form of near-instant evolution that provides life with a third way to adapt to potentially lethal environments. Crucially, it involves neither genetic nor epigenetic changes to DNA.

The conventional view is that new traits can only evolve if DNA itself changes in some way. The classic way to do this is by mutating the genetic code itself. More recently, researchers have discovered that molecules can clamp onto DNA and prevent some parts of the sequence from being read, leading to genetic changes through a process that is known as epigenetics.

Yeast breaks the mould. In challenging conditions, it can instantly churn out hundreds of brand-new and potentially lifesaving proteins from its DNA, all without changing the genes in any way. Instead, yeast alters the way its DNA is read. The tiny fungi convert a special type of protein called Sup35 into a prion.

Sup35 normally plays an important role in the protein production line. It makes sure that the ribosomes within cells, in which the proteins are built, start and stop reading a DNA strand at just the right points to generate a certain protein.

When Sup35 transforms into a prion, it no longer performs that role. With this quality control missing, the entire gene sequence is read as it spools through the ribosome. This generates new proteins from sections of DNA that are usually ignored (see diagram).

The result is that the yeast generates a hotchpotch of brand-new proteins without changing its DNA in any way. Within that mix of new proteins could be some that are crucial for survival.

Susan Lindquist at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, first saw this process, which she calls "combinatorial evolution", in 2004, while studying lab-grown Baker's yeast (Saccharomyces cerevisiae).

"We've been saying this is really cool and a way of producing new traits for years, but other people have said it's a disease of lab yeast," she says.

Now she's proved the sceptics wrong by demonstrating beyond doubt that the same process happens in nature too. She has seen it at work in 255 of 700 natural yeasts she and her colleagues have studied (Nature, DOI: 10.1038/nature10875).

Lindquist grew the yeast in a hostile environment - either oxygen-depleted or abnormally acidic, for example - and then exposed the survivors to a chemical that destroys prions. Many colonies withered, showing that the prions were responsible for their competitive edge.

What's more, the prions are passed down in mating, so daughter cells will also make the same suite of survivor proteins.

"First and foremost it's an adaptive strategy," says Lindquist. "It's a great way of acquiring new [physical traits]."

Lindquist says that it is even possible for the production of the new proteins to become "hard-wired" into the genome, through mutation in the genetic code, although she has yet to see this happen.

Other researchers are impressed. "It is truly amazing," says Yury Chernoff of the Georgia Institute of Technology in Atlanta, and one of the researchers who previously suspected that combinatorial evolution was a lab artefact.

"It means that 'protein mutations', or prions, have a strong impact on [the physical appearance of an organism], so not all evolution is occurring through a DNA change," Chernoff says.

Right now, it is unclear whether combinatorial evolution is a quirk of yeast biology or a more general fact of life, but researchers are hopeful that the latter is true.

"Prions could very well play an important role in natural evolution," speculates Rong Li at the Stowers Institute for Medical Research in Kansas City, Missouri, who recently found that yeast can also evolve by shuffling chromosomes.