The “Awesome Power” of Yeast: An Almost Perfect Match

The “Awesome Power” of Yeast: An Almost Perfect Match

Posted by Biomechanism 

(Biomechanism.com)– Yeast has been known and loved by human beings since ancient times. When added to mashed-up wheat, it makes bread rise. When added to squashed grapes, it produces wine. Its warm, slightly fruity smell is the smell of live cells at work. Even a slim package of “active dry” yeast contains roughly 35 billion cells of Saccharomyces cerevisiae (baker’s or brewer’s yeast), and as soon as these cells find food, they produce fermentation bubbles—the bubbles that cause dough to rise or beer to foam.

The 3-D structures of many yeast and mammalian proteins are nearly identical. Here the structure of the yeast actin (yellow) is superimposed on the structure of the mammalian actin, a muscle protein (blue), and fits almost perfectly. Image: Sergey Vorobiev

Yeast is also plentiful. When you eat grapes, you swallow millions of live yeast cells that were feasting on sugar on the grapes’ surface. Yeast is cheap. It’s easy to grow—yeast cells double every 90 minutes when food is available, and billions of them will fit in a few petri dishes.

Not only are these cells alive (until oven heat kills them), they can do almost everything that human cells do to survive: transmit signals from the cell’s surface to its nucleus, manufacture thousands of proteins, create a cellular scaffolding, repair DNA in the nucleus, and so on. And although yeast cannot make tissues and does not have a brain, it is universally recognized as the best model organism for studies of anything that goes on inside a single cell.

Researchers speak glowingly of the “awesome power” of yeast genetics to solve problems in biology. “It’s so easy with yeast!” says Randy Schekman, an HHMI investigator at the University of California, Berkeley. He points out that “genetic surgery has been possible in yeast for 20 years. You can stitch bits of DNA from a normal yeast cell onto a plasmid, the plasmid will carry this DNA into a mutant yeast cell, and the normal yeast gene will replace the mutant one at precisely the right place.”

It’s also very quick. The yeast genome has so few genes—6,000, compared with the estimated 40,000 genes in mice and humans–and the tools for manipulating these genes are so highly developed that yeast experiments can generally be performed in days or weeks. Similar experiments in mice might take years—if they could be done at all.

Another great virtue of yeast is that its genes have very few of the bothersome introns (intervening sequences of DNA) that interrupt the coding sequences of mammalian genes. This makes it “easy to recognize where the genes are in yeast and what their boundaries are, just by looking at the genome sequence,” Pat Brown explains. He notes that approximately 70 percent of the yeast genome codes for protein—a huge amount, compared with only 5 percent of the human genome. (The function of the remaining 95 percent of the human genome is still unknown.)

Despite these differences, large numbers of yeast genes closely resemble those of mice and humans. They also produce nearly identical proteins. “You can generally take a yeast protein and an equivalent human protein and superimpose their 3-D structures, and they will be crystallographically the same,” says David Botstein. In his studies of actin, a protein, Botstein found that “not only is actin conserved [unchanged by evolution] from yeast to humans but most of the proteins that interact with actin in yeast are also conserved, and so are their interactions.”

Philip Hieter of the University of British Columbia in Vancouver, a pioneer of what he calls “comparative genomics,” remembers that when he gave talks about yeast in the 1980s, “there was a lot of skepticism. People didn’t appreciate how similar yeast was to mammals. But the next 10 years showed that all the basic pathways within cells are much more conserved than anybody expected at the time.

So if you examine a new human protein—a protein involved in a human disease, let’s say—and you find that it matches a yeast protein, this brings up the entire biochemical pathway.” For a biomedical scientist, that’s like hitting a jackpot.