Researchers Create Artificial Eukaryotic Chromosome
Researchers led by Dr Jef Boeke of NYU Langone Medical Center’s Institute for Systems Genetics have synthesized the first functional chromosome in brewer’s yeast known scientifically as Saccharomyces cerevisiae.
Over the last five years, scientists have built bacterial chromosomes and viral DNA, but this is the first report of an entire eukaryotic chromosome, the thread-like structure that carries genes in the nucleus of all plant and animal cells, built from scratch.
The study also marks one of the most significant advances in yeast genetics since 1996, when scientists initially mapped out yeast’s entire DNA code, or genetic blueprint.
Dr Boeke and his colleagues built a fully functioning chromosome, which they call synIII, and successfully incorporated it into Saccharomyces cerevisiae.
The effort to construct synIII tied together some 273, 871 base pairs of DNA, shorter than its native yeast counterpart. The 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.
Yeast shares roughly a third of its 6,000 genes – functional units of chromosomal DNA for encoding proteins – with humans.
The scientists were able to manipulate large sections of yeast DNA without compromising chromosomal viability and function using a so-called scrambling technique that allowed the scientists to shuffle genes like a deck of cards, where each gene is a card.
“We can pull together any group of cards, shuffle the order and make millions and millions of different decks, all in one small tube of yeast. Now that we can shuffle the genomic deck, it will allow us to ask, can we make a deck of cards with a better hand for making yeast survive under any of a multitude of conditions, such as tolerating higher alcohol levels,” said Dr Boeke, who is the senior author of a paper published in the journal Science.
Using the scrambling technique, researchers will be able to more quickly develop synthetic strains of yeast that could be used in the manufacture of rare medicines, such as artemisinin for malaria, or in the production of certain vaccines, including the vaccine for hepatitis B, which is derived from yeast. Synthetic yeast, they say, could also be used to bolster development of more efficient biofuels, such as alcohol, butanol, and biodiesel.
“The study will also likely spur laboratory investigations into specific gene function and interactions between genes, in an effort to understand how whole networks of genes specify individual biological behaviors,” Dr Boeke said.