Saturday, January 31, 2015

Inheritance Without Genes? Yeast Does It With Proteins

The big hole in Darwin's theory of natural selection was the mechanism by which parents could transmit traits to their offspring, along with enough variation to allow selection to work. DNA seemed to be the answer, but new research shows it may not be the only way.

Inheritance Without Genes? Yeast Does It With Proteins

Scientists have long wondered why our brains contain proteins called prions, which from a medical standpoint seem like a huge liability. The prions in our brains make us vulnerable to mad cow disease and other brain wasting conditions that are caused by misfolded versions of these prions that clump up. It was a shock to the scientific community that any infection could be transmitted not by an organism but by a protein - an inanimate molecule. That discovery eventually led to a Nobel Prize for biologist Stanley Prusiner. 

Now, research published yesterday in the journal Nature shows that yeast cells carry prions that can enhance survival, helping the organisms adapt to stressful conditions. Prions not only spread disease, they can also pass traits from one generation to the next. In doing so, they may allow an alternative mechanim for evolution to proceed.  

Science News has a nice summary of the research, which used 700 strains of yeast to show that prions can pass on traits, possibly allowing the cells to "try out" changes without committing them to the genetic code. 

In yeast, prions cause a wide variety of new characteristics that are not wired into DNA but can still be passed on to daughter cells. The changes might act like prototypes that cells can try out before incorporating them into nucleic acid, scientists at the Whitehead Institute for Biomedical Research in Cambridge, Mass. report in the Feb. 16 Nature.

“This is opening up a whole new world of work for scientists and a whole new world for people to understand how evolution occurs,” says Yury Chernoff, a biologist at the Georgia Institute of Technology.

Meanwhile Nature offers a fascinating profile of the lead researcher on the project, Susan Lindquist. This passage explains the role of a prion called Hsp104, which tends to clump in fibers: 

 Short segments of these Sup35 fibres are passed to daughter cells and act as a template for more to form. Watching the yeast prions pass from mother cell to daughter cell was “pretty magical”, Lindquist says. Moreover, the results suggested that simple yeast cells could be used to study the proteins that cause neurodegenerative disorders in humans — another idea that colleagues found hard to swallow.

Many have suggested that the prions she has been observing are artefacts of laboratory culture techniques that force proteins to behave in unnatural ways. But in her most recent paper1, Lindquist has shown that about one-third of the 700 or so wild yeast strains she examined harboured prions. In almost half of those strains, the prion seems to confer a beneficial trait. For example, a strain isolated from white wine is resistant to acidic environments and to the anti-fungal drug fluconazole; and a strain harvested from Lambrusco grapes is resistant to a DNA-damaging agent. When the prions in these strains are eradicated or 'cured', these useful traits disappear.

Lindquist has also continued her studies of Hsp90. When, in the 1990s, she disabled, or knocked out, both copies of the gene that makes Hsp90 in fruitflies, the creatures died; but when she knocked out just one copy, something mysterious happened. Flies were born with a hodgepodge of physical deformities, such as shrunken or square eyes, shrivelled wings and crooked legs7.

Lindquist calls Hsp90 a “capacitor” for evolutionary change. Just as an electrical capacitor stores electrical energy, Hsp90 lets hidden variation build up in the genome. When an environmental stressor trips the switch, dramatic variations can be unleashed. She found the same kinds of effects in the plant Arabidopsis thaliana — upturned and extra roots, exotic leaf whorls and darker hues appeared when the heat-shock protein system was put under stress8. Lindquist suggests that studying this phenomenon would be a powerful approach for discovering hidden variation in plants — unlocking the basis of traits such as drought resistance or salt tolerance.

Darwin didn't know what the mechanism was for passing traits from parents to offspring. DNA seemed to offer the answer, but life may have adopted other mechanisms as well. DNA changes can carry traits on for hundreds of millions of years, but other mechanisms could create less stable but more flexible changes. 

It's not clear from this whether our prions can offer us any benefit, or wheher we inherited them from organisms that benefitted from them. Either way, it's an exciting line of research. 

About this blog
Faye Flam - writer
In pursuit of her stories, writer Faye Flam has weathered storms in Greenland, gotten frost nip at the South Pole, and floated weightless aboard NASA’s zero-g plane. She has a degree in geophysics from the California Institute of Technology and started her writing career with the Economist. She later took on the particle physics and cosmology beat at Science Magazine before coming to the Inquirer in 1995. Her previous science column, “Carnal Knowledge,” ran from 2005 to 2008. Her new column and blog, Planet of the Apes, explores the topic of evolution and runs here and in the Inquirer’s health section each Monday. Email Faye at fflam@phillynews.com. Reach Planet of the at fflam@phillynews.com.

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