Synthetic biologist create first man-made yeast chromosome

By on April 2, 2014

Yeast has been used by humans since earliest stages of modern society. We manipulated its characteristics to make our bread rise and to make our alcohol taste good. Now, we are taking our relationship with yeast to a whole new level.

Manipulating yeast characteristics is one thing but Jef Boeke, a researcher with New York University’s medical center and his team, has created a functional yeast chromosome from scratch.

Unlike previous attempts at synthesizing genes and DNA, the new method is much more powerful. For example, Boeke and his team can use a technique they call “genome scrambling system” to shuffle the yeast genes like a deck of cards to create various new features and abilities.

It comes as no surprise that this remarkable step in synthetic biology would first come with yeast chromosomes.

“We have this ancient industrial relationship with this organism,” Boeke stated.

Additionally, synthesizing DNA is not new. In 2010 the J. Craig Venter Institute built all the DNA of a bacteria from scratch.

This recent step in synthetic biology made the leap, however, from the prokaryotic world with bacteria to the eukaryotic world with yeast.

Eukaryotic cells are far more complex, as, unlike prokaryotes, they contain nuclei, copious amounts of “junk DNA,” and large protein processing mechanisms. The road to building this synthetic DNA was no small task.

The entire project took the researchers seven years, most of which was used to manually piece the DNA “letters” – adenine, thymine, guanine, and cytosine – together. Knowing this, the researchers tackled one of the smallest chromosomes of yeast available – chromosome III of brewer’s yeast. This chromosome, normally 316,617 base pairs long, is responsible for controlling cell mating.

The group used computer software to create a modified version of chromosome III with over 500 changes, resulting in a chromosome III that consists of only 272,871 base pairs. One of the important changes made was the removal of junk DNA, which is not known to encode any proteins.

Another was the inclusion of the so-called jumping genes that have the ability to move around the chromosome randomly. Most importantly, though, was the inclusion of DNA tags to separate their synthetic from the native once they placed their synthetic chromosome into an actual yeast cell.

Most of the “leg work” in putting the letters together was done by a group undergraduate of students at Johns Hopkins University for a class project. The project was very successful, and Boeke describes the completed chromosome as “remarkably normal” and that it “behave[s] almost identically to wild yeast cells.” With one synthetic chromosome completed, the team is setting its sight on eventually synthesizing all 16 chromosomes.

Amidst all the excitement over being able to synthesize the chromosome, Boeke believes the true discovery lies in the DNA-scrambling technology. He believes the technology will allow bioengineers to make yeast that are more efficient and hardier, and the ability to “write” DNA into organisms can open up many doors to the scientific future.

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