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Prions point to a new style of evolution
THIS WEEK
Andy Coghlan
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
Lifesaving prions Yeast can adapt to new environments by changing the way its DNA is read NORMAL YEAST CELL Sup35 protein starts and stops reading of DNA within ribosome DNA
START
STOP
RIBOSOME PROTEIN MADE EFFECT OF PRION When Sup35 becomes a prion it no longer “stops” DNA being read. The entire strand is read, producing novel proteins in a bid for survival Non-stop reading
NEW PROTEINS MADE 14 | NewScientist | 18 February 2012
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 seen it at work in 255 of 700 natural yeasts she and her is read as it spools through the colleagues have studied (Nature, ribosome. This generates new DOI: 10.1038/nature10875). proteins from sections of DNA Lindquist grew the yeast in a that are usually ignored (see hostile environment – either diagram, left). oxygen-depleted or abnormally The result is that the yeast acidic, for example – and then generates a hotchpotch of brandnew proteins without changing its exposed the survivors to a chemical that destroys prions. DNA in any way. Within that mix Many colonies withered, showing of new proteins could be some that the prions were responsible that are crucial for survival. Susan Lindquist at the “Yeast can generate a Whitehead Institute for Biomedical Research in Cambridge, hotchpotch of brand-new Massachusetts, first saw this proteins without changing process, which she calls its DNA in any way” “combinatorial evolution”, in 2004, while studying lab-grown for their competitive edge. Baker’s yeast (Saccharomyces What’s more, the prions are cerevisiae). passed down in mating, so “We’ve been saying this is really daughter cells will also make the cool and a way of producing new same suite of survivor proteins. traits for years, but other people “First and foremost it’s an have said it’s a disease of lab adaptive strategy,” says Lindquist. yeast,” she says. “It’s a great way of acquiring new Now she’s proved the sceptics [physical traits].” wrong by demonstrating beyond Lindquist says that it is even doubt that the same process possible for the production of happens in nature too. She has the new proteins to become
gene cox/spl/getty
Evolution’s third way down to prions
–Yeast get the edge with prions–
“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. n
Andy Coghlan
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
Lifesaving prions Yeast can adapt to new environments by changing the way its DNA is read NORMAL YEAST CELL Sup35 protein starts and stops reading of DNA within ribosome DNA
START
STOP
RIBOSOME PROTEIN MADE EFFECT OF PRION When Sup35 becomes a prion it no longer “stops” DNA being read. The entire strand is read, producing novel proteins in a bid for survival Non-stop reading
NEW PROTEINS MADE 14 | NewScientist | 18 February 2012
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 seen it at work in 255 of 700 natural yeasts she and her is read as it spools through the colleagues have studied (Nature, ribosome. This generates new DOI: 10.1038/nature10875). proteins from sections of DNA Lindquist grew the yeast in a that are usually ignored (see hostile environment – either diagram, left). oxygen-depleted or abnormally The result is that the yeast acidic, for example – and then generates a hotchpotch of brandnew proteins without changing its exposed the survivors to a chemical that destroys prions. DNA in any way. Within that mix Many colonies withered, showing of new proteins could be some that the prions were responsible that are crucial for survival. Susan Lindquist at the “Yeast can generate a Whitehead Institute for Biomedical Research in Cambridge, hotchpotch of brand-new Massachusetts, first saw this proteins without changing process, which she calls its DNA in any way” “combinatorial evolution”, in 2004, while studying lab-grown for their competitive edge. Baker’s yeast (Saccharomyces What’s more, the prions are cerevisiae). passed down in mating, so “We’ve been saying this is really daughter cells will also make the cool and a way of producing new same suite of survivor proteins. traits for years, but other people “First and foremost it’s an have said it’s a disease of lab adaptive strategy,” says Lindquist. yeast,” she says. “It’s a great way of acquiring new Now she’s proved the sceptics [physical traits].” wrong by demonstrating beyond Lindquist says that it is even doubt that the same process possible for the production of happens in nature too. She has the new proteins to become
gene cox/spl/getty
Evolution’s third way down to prions
–Yeast get the edge with prions–
“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. n