First functional 'designer chromosome' in yeast developed from scratch

Researchers have synthesized the first functional chromosome in yeast, an important step in the emerging field of synthetic biology, designing microorganisms to produce novel medicines, raw materials for food, and biofuels.

Jef Boeke, PhD, director of NYU Langone Medical Center's Institute for Systems Genetics, said it is the most extensively altered chromosome ever built. But the milestone that really counts is integrating it into a living yeast cell.

He said they have shown that yeast cells carrying this synthetic chromosome are remarkably normal. They behave almost identically to wild yeast cells, only they now possess new capabilities and can do things that wild yeast cannot.

The team reports used computer-aided design to build a fully functioning chromosome, which they call synIII, and successfully incorporated it into brewer's yeast, known scientifically as Saccharomyces cerevisiae.

The seven-year effort to construct synIII tied together some 273, 871 base pairs of DNA, shorter than its native yeast counterpart, which has 316,667 base pairs.

Dr. Boeke and his team made more than 500 alterations to its genetic base, removing repeating sections of some 47,841 DNA base pairs, deemed unnecessary to chromosome reproduction and growth. Also removed was what is popularly termed junk DNA, including base pairs known not to encode for any particular proteins, and "jumping gene" segments known to randomly move around and introduce mutations.

Other sets of base pairs were added or altered to enable researchers to tag DNA as synthetic or native, and to delete or move genes on synIII.

Yeast chromosome III was selected for synthesis because it is among the smallest of the 16 yeast chromosomes and controls how yeast cells mate and undergo genetic change. DNA comprises four letter-designated base macromolecules strung together in matching sets, or base pairs, in a pattern of repeating letters. "A" stands for adenine, paired with "T" for thymine; and "C" represents cysteine, paired with "G" for guanine. When stacked, these base pairs form a helical structure of DNA resembling a twisted ladder.

The study has been published online in the journal Science.