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Lamarckism finds new lease of life in a prion

EVOLUTION can occur in a way never previously shown. Geneticists have discovered that the strange proteins called prions can temporarily give yeast cells new powers which can then be quickly, and permanently, assimilated into their chromosomes.

“This provides a novel way for organisms to try out different traits, survive and adapt to fluctuating environments,” says Susan Lindquist who led the work at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. The finding unexpectedly brings together the theories that Charles Darwin and his chief rival Jean-Baptiste Lamarck developed to explain evolution.

Translated into modern terms, Darwin’s theory of natural selection states that organisms with genes more suited to their environment survive, passing those genes on to their offspring, while those with unfit genes perish. In that way, a species becomes more attuned to its environment with each generation. Genes are involved in most matters of heredity, so Darwin was proved correct.

In contrast, Lamarck believed that organisms could acquire new traits during their lives which would then be inherited. His theory suggests that no change in DNA or genes is necessary, and neither is the culling force of natural selection. Various forms of this type of inheritance have been shown in recent years to occur in a variety of organisms, a mechanism known as “epigenetic”.

Now Lindquist has shown that in yeast at least there is another way that adaptive traits can be passed on, involving a combination of genetic and epigenetic inheritance. And it is triggered by prions, proteins that can change shape, assuming a conformation which coaxes other proteins to form that shape, too.

Lindquist examined the role of a protein called Sup35 in the yeast Saccharomyces cerevisiae which normally makes certain that “junk” regions of the genome are not used to make proteins. When Sup35 forms a prion it becomes sloppy in its work, allowing proteins to be made from previously unused pieces of DNA.

Lindquist’s team showed that a surprising proportion of yeast cells containing Sup35 prions, about 20 per cent, acquired new adaptive powers, such as resistance to the herbicide paraquat. Using sophisticated genetic techniques, her team was then able to remove the prion and show that the resistance also disappears. No change had occurred in the cell’s DNA. Instead the presence of the Sup35 prion meant that unused portions of the yeast genome were switched on to code for new protein regions that conferred resistance to the herbicide.

But even more surprising was what happened when these cells were mated to another strain with no paraquat resistance. Some of the progeny quickly acquired the ability to resist the herbicide – even when they did not contain the prion (Nature, DOI: 10.1038/nature02885). Lindquist believes that the reshuffling of genes that occurs in sexual reproduction allowed new genetic combinations to form that are resistant to the drug. “Without the prion, these cells would not have survived to mate and find those new genetic combinations,” she says. So the epigenetic inheritance supported by prions provided a route for selection of new gene combinations, mating Larmarckian and Darwinian notions of evolution.

Even so, prion researcher Yuri Chernoff of the Georgia Institute of Technology in Atlanta says it remains unclear whether this type of evolution occurs outside the laboratory, and in organisms other than yeast. “But that does not diminish the importance of this work in revealing a specific mechanism for this type of inheritance.” Lindquist points out that the Sup35 protein seems to have retained its ability to turn into a prion over some 400 million years of fungal evolution, suggesting the prion provided some advantage.

Experts already think other epigenetic mechanisms may have shaped the evolution of more complex organisms (èƵ, 28 November 1998, p 26). “I wouldn’t be surprised if this happens in people as well. This is the tip of the iceberg,” Lindquist says.

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