'Partly human yeast' may hold key to some genetic diseases

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Image of a yeast cell. Photo credit: Col Ford and Natasha de Vere. Image rights: Creative Commons

It is a central axiom of biology that all living things on the planet are – however distantly – related.

A fascinating new study is proposing new ways to combat genetic diseases, taking advantage of humankind’s surprisingly strong common ancestry... with baker’s yeast.

“It doesn’t look anything at all like humans, but yeast is a very, very distant cousin, separated a billion years ago,” Prof. Edward Marcotte of the the Department of Molecular Biology at the University of Texas at Austin tells Yahoo Canada.

“But we still share a lot of genes in common.”

Around 4,000 genes, it turns out. That’s one-fifth of the 20,000 genes that make up the human genome.

“The test that we did was to take yeast cells, break the yeast gene, and provide it with DNA from the human equivalent,” Marcotte explains. “We put in the corresponding human DNA, then asked whether the human DNA could keep the cells alive?”

“We tested a little under 500 such pairs of genes between humans and yeast, and almost half of them work perfectly well.”

Image of a 'humanized' yeast cell. Illustration: Jacqui Tabler.

The possibilities for medical research are intriguing. If human genes associated with a particular genetic condition could be successfully transplanted into yeast, the yeast could then be used to test new drugs.

“This gives us, essentially, a test tube to test whether different versions of that human gene are functional or not,” he continues. “Yeast grow overnight – very, very rapidly. And it’s very simple to go in and manipulate all aspects of their DNA. They only have a single cell, so it’s a much faster process to do all of these tests.”

There is a lot of trial and error in any form of genetic testing or research. Yeast has a formidable flexibility that makes exact targeting simple.

“We could, in principle, use these strains to try to discover drugs that are active to either turn up or turn down a specific human gene, or against different versions of the human gene.”

It’s not yet known which specific genetic conditions could be treated this way. The 20 per cent genetic overlap between humans and yeast is useful, but far from all-encompassing. Many ailments and diseases will remain, for now, unaffected.

“Within that overlap we have got, for example, a lot of the cholesterol biosynthesis genes. You think of cholesterol as something you take in in your diet. But it’s actually a critical part of your cells’ membranes that helps them keep their shape and form and function. You make cholesterol within your body to help your cells stay healthy. And that system was one of the ones that was almost completely replaceable, gene by gene, in the yeast we had given the human genes.”

Encouragingly, there has already been some drug-development success.

“On the drug side, we have one case, a few years ago, where we were actually able to discover a new drug from yeast,” says Marcotte. “We now have an FDA-approved vascular disrupting agent. So that’s a reasonable prospect for moving forward.”

Similar work is being done in other areas of gene transplantation, as well.

“The strategy is starting to be used for cancer chemotherapy,” he notes. “There are a number of institutions around the world trying to set in place the ability to take a biopsy of somebody’s tumour, figure out what mutations they have, and then build those mutations into a fly or a worm. Then they can do drug screens on them, to know what drugs that tumour might respond to.”