In a biological first, an international team has inserted a man-made chromosome into brewer's yeast, producing a life form that thrives and successfully passes the designer genes on to its offspring.
The "synthetic" biology advance—the first synthesis of a working artificial chromosome in an organism more complex than a bacterium—opens the door wider to man-made microbes that may someday be designed to manufacture better fuels, food, and medicines. (Related: "Rewiring Life: Learning About Synthetic Biology.")
"We can shuffle genes into these chromosomes like a deck of cards," says Jef Boeke of the NYU Langone Medical Center's Institute for System Genetics, who led the study reported in the journal Science.
Comparing a chromosome to a chapter in a book filled with genes, Boeke said, "we have changed the letters of this chromosome [just] as we would in a book." (Related: "How to Turn Gut Bacteria Into Journalists.")
Chromosomes are the packages for genes. In plants, animals, and fungi like yeast, they are contained within a cell nucleus, which simpler microbes like bacteria do not have. People have 23 pairs of chromosomes, and yeasts have 16. Best known for their role in baking bread and brewing beer, yeasts share about a third of their genes with people.
Tolerant of genetic tinkering, yeast played a role in a previous synthetic biology breakthrough, when scientists led by J. Craig Venter assembled the first artificial bacterial genome inside yeast cells in 2009. And man-made DNA strips cooked up inside yeasts, so-called yeast artificial chromosomes (YACs), have been used to make gene maps for decades. Yeast was one of the first organisms to have its entire genome sequenced, in 1996.
The new study's "synIII" artificial chromosome implanted into brewer's yeast builds on this legacy. It crowns a seven-year "Build a Genome" project that involved more than 60 biologists in its assembly.
Essentially, the study researchers created a stripped-down, but still functional, third chromosome of brewer's yeast, which contains about 2.5 percent of the organism's total genes.
The scientists never inserted thousands of letters of repetitive genetic code seen in wild yeast from their artificial version of the chromosome. When they inserted it into living yeast cells, the synthetic chromosome was copied in the microbe's offspring along with their natural chromosomes through some 125 generations, proving its stability.
This is "a major step towards being able to design completely novel organisms," says Todd Kuiken of the Woodrow Wilson International Center for Scholars in Washington, D.C. "The research team has created what some might call the first synthetic cell that was designed, built and reproduced without a host cell present," he says, by email.
"This is significant as an example of synthetic genomics aimed well beyond making mere copies of chromosomes—the new trend being the making of significant functional changes—ideally changes useful for biotech productivity and safety," says Harvard biologist George Church, who was not part of the study.
Still awaiting scientists is the assembly of a complete artificial genome: man-made versions of all the chromosomes in a plant or animal, Church adds.
Brave New Biology
Ideally, synthetic biology will produce microbes with specific genetic codes embedded to cheaply churn out renewable fuels or medicines such as the antimalarial drug artemisinin.
Despite the excitement, only about 23 percent of U.S. respondents had heard a good deal about synthetic biology in a 2013 survey, Kuiken notes. About 30 percent said they had heard nothing at all.
The science has also conjured worries about bioterror bugs crafted to combine plague with other maladies, a worry that led leading members of the field to tackle ethics projects over the last decade, and is the subject of a report from the President's Bioethics Council.
"We are entering a new era in biotechnology," Boeke says. "This is just the beginning of a whole series of products in the works that spring from the ancient relationship between humans and yeast."
Follow Dan Vergano on Twitter.