New Type Of DNA-Free Inheritance In Yeast Is Spread By A "Mad Cow" Mechanism

May 30, 1997

Researchers at the University of Chicago's Howard Hughes Medical Institute have found that a protein molecule able to transmit a genetic trait without DNA or RNA in yeast is able to string itself together into long fibers much like those found in the brain in "mad cow" and human Creutzfeldt-Jakob diseases.

The finding is reported in the May 30 issue of the journal Cell.

Scientists have suspected that in the neurodegenerative diseases of mammals such as sheep scrapie, mad cow disease (or bovine spongiform encephalopathy) and the kuru disease of the Papua New Guinea tribes, a normal protein in the brain can somehow become twisted and then corrupt other, healthy molecules of the same protein to do likewise a process much like the seeding of a crystal. The improperly folded protein molecules seem to spin themselves together into fibers, which grow as other molecules are recruited.

The infectious protein particles are called prions, and their existence has been hotly debated for 30 years, since researchers showed that diseased brain tissue remained infectious even after treatment with radiation that would have destroyed any DNA or RNA.

Last year the Chicago team led by Susan Lindquist, Ph.D., professor of molecular genetics and cell biology, showed that prion-like proteins exist in yeast. In the mammalian brain, whose cells do not divide, prions pass between cells and function as infectious agents; in yeast, they produce heritable changes in metabolism from one generation to the next as the cells divide. The change is easy to see, because in one case the cells are red and in the other white.

"That a genetic property carried by protein shape can be responsible for inheritance from generation to generation or for an infection is a revolutionary concept," Lindquist said.

Lindquist's group focused on a yeast protein called sup35, part of the normal yeast machinery for making all the other proteins in the cell. In certain strains which appear to have identical DNA to normal strains the sup35 protein doesn't work. They showed that the defective trait can be propagated by this faulty protein, without any DNA or RNA serving as the genetic blueprint. They now show that even in the test tube, the purified yeast protein can knit together into fibers that have the same staining properties and molecular architecture as the amyloid plaques seen at autopsy in the brains of animals and humans that have died of transmissible spongiform encephalopathies. They also show that the formation of fibers from normal protein molecules is greatly speeded up by the presence of defective ones.

"Instead of a vague conceptual model for this new type of inheritance, we now have a detailed molecular mechanism for this mysterious process," Lindquist says, "and this seems to be closely related to the mechanism behind these devastating neurodegenerative diseases."

Although the yeast sup35 protein and the mammalian prion protein are not at all related to each other the yeast pose no risk to consumers of bread or beer the researchers think that in-depth analysis of the yeast prion-like elements and other proteins that help them fold up may lead to new approaches to therapies for neurodegenerative diseases.

"From the molecular standpoint, this looks like the changes you get in the mammalian prion," said research associate John Glover, Ph.D., lead author on the Cell paper. "This gives us a clear structural basis for understanding how these things behave in the cell," he said.

The researchers said it is much cheaper and easier to study genetic mechanisms in yeast than in animals.

Lindquist said that the ability of certain proteins to confer heritable properties by changing their shape may underlie other unexplained genetic phenomena. A similar protein misfolding that is not infectious seems to cause Alzheimer's disease.

Other authors on the Cell paper include electron microscopist Anthony Kowal, graduate students Eric Schirmer and Jia-Jia Liu, and research associate Maria Patino, Ph.D. The research was funded by the Howard Hughes Medical Institute and the National Institutes of Health.

University of Chicago Medical Center

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.