Yeast and humans have been evolving along separate paths for 1 billion years, but there’s still a strong family resemblance, a new study demonstrates. After inserting more than 400 human genes into yeast cells one at a time, researchers found that almost 50% of the genes functioned and enabled the fungi to survive.
“It’s quite amazing,” says evolutionary biologist Matthew Hahn of Indiana University, Bloomington, who wasn’t connected to the study. “It means that the same genes can carry out the same functions after 1 billion years of divergence.”
Scientists have known for years that humans share molecular similarities with the microorganisms that help make our bread and beer. Our genome contains counterparts to one-third of yeast genes. And on average, the amino acid sequences of comparable yeast and human proteins overlap by 32%.
One example of shared genes piqued the interest of systems biologist Edward Marcotte of the University of Texas, Austin, and colleagues. Yeasts are single-celled and bloodless, yet they carry genes that orchestrate the growth of new blood vessels in vertebrates. In yeast, these genes help cells respond to stress. “That got us questioning the extent to which the yeast and human genes are doing the same thing,” Marcotte says.
To find out, he and his team decided to check systematically whether human genes can operate in yeast. The researchers picked 414 genes that the fungi can’t live without—genes that help control metabolism and dispose of cellular junk, for example. Then they slipped a human version of each gene into yeast cells whose own copy of the gene had been turned down, turned off, or removed. If the cells grew on culture plates, the team inferred that the human gene could fill in for its yeast equivalent.
The researchers determined that 176 of the human genes allowed yeast to survive the loss of a vital gene. “About half of these [genes] can be swapped … between humans and yeast and they still work,” Marcotte says. “It beautifully illustrates the common heritage of living things.”
He and his colleagues next asked what distinguishes the replaceable genes. They evaluated more than 100 possible influences, from the length of the gene to the abundance of its protein. The degree of DNA similarity didn’t necessarily indicate whether a human gene could stand in for a yeast gene, Marcotte and colleagues reveal online today in Science. Instead, they found, when a bunch of genes work closely together, either most of them are replaceable or most of them aren’t. For example, every gene in a pathway that instigates DNA copying was irreplaceable, but almost all the genes in the molecular pathway that in humans manufactures cholesterol could be swapped.
“I was impressed by the amount of work” the researchers put in, says molecular geneticist Bernard Dujon of the Institut Pasteur in Paris. Although the results of the study weren’t surprising, he says, “I’m glad somebody has done it.”
The team showed only that yeast equipped with human genes could survive, not that they were vigorous and could compete with unaltered strains, cautions Eugene Koonin, an evolutionary biologist at the National Center for Biotechnology Information in Bethesda, Maryland. Nonetheless, he says, the study provides strong support for the idea—which some researchers have challenged—that comparable genes in different organisms have similar functions.
Marcotte says the findings suggest further ways to harness yeast for research. Scientists often study individual human genes by inserting them into yeast cells. But they could also transplant groups of interacting genes, creating more humanlike yeast that would be useful for studying new drugs or molecular circuits that go awry in diseases.