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Synthetic DNA – now in yeast!

The views expressed are those of the author and are not necessarily those of Scientific American.


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iGEM season is here and so to get into the spirit of things I thought I’d see if any interesting synthetic biology news had happened recently. It turns out that while I’ve been getting all excited about bacteria, people doing research on yeast have managed something pretty spectacular – they’ve replaced a whole section of a yeast chromosome with artificial DNA (ref. 1).

This may not sound too exciting to those who remember that recently Craig Venter swapped the entire genome of a bacteria for synthetic DNA, but with the yeast there are several vital differences. Firstly, the yeast genome is much bigger, usually over an entire order of magnitude larger than the bacterial genome. Secondly whilst the bacterial genome is in one circular loop, the yeast DNA is divided up into linear chromosomes, much like in human cells.

chromosome

A cartoon of a single chromosome, with one arm (the amount synthesised) surrounded by a red box. Image modified from wikimedia commons

The researchers decided to concentrate on yeast as it is one of the best studied eukaryotes on the planet. Because of its use in brewing, baking and other industries, as well as how easy it is to grow, yeast has been studied and examined more  conclusively than most bacteria. Working with the smallest arm on chromosome IX (haploid yeast has 16 chromosomes in total) they designed a section of synthetic DNA which would confer no phenotypic differences upon the yeast.

The DNA was then synthesised according to the design pattern and inserted as a large chunk into normal yeast, where the synthetic DNA replaced the non-synthetic section of the genome. The yeast could grow normally and healthily with this partially-synthetic genome.

budding yeast cell

A yeast cell in the act of 'budding'. The small circle attached is a daughter cell which will break off and grow to full size.

The great thing about synthetic genes is that you can design them to do all sorts of interesting things once they’re inside the organism. The ability that the researchers conferred upon the section of yeast genome was the ability to ‘scramble’. At the addition of certain enzymes, the man-made genome would slice itself up, chopping and changing the genes to produce novel sections of DNA. This can be compared to re-shuffling a deck of cards; the samegenes are still all present, but in new and exciting combinations.

As this is the largest section of eukaryote DNA ever synthesised, this work has fascinating potential. I got in touch with Professor Boeke and he was kind enough to explain what he saw as the future potential of his work. Firstly, to “study fundamental biology problems difficult to answer in other ways” such as the minimal size of a yeast genome and how the structure of a yeast chromosome relates to its function and gene expression. Secondly “to help make yeast more flexible as a fermentation system for efficiently manufacturing useful products, such as medicines, vaccines and biofuels.”

Much as I love bacteria, I am willing to admit the their potential for large scale fermentation is limited. With yeast there is already a whole industry dedicated to the collection of the products of fermentation, and the development of the most efficiently fermenting yeast. The introduction of synthetic genes to make natural products would be taking advantage of this huge fermentation power and is a wonderful argument for continuing research into the synthetic manipulation of yeast.

Many thanks to Professor Boeke for helping to explain the research and for providing a quote on the future potential of this work. His lab homepage can be found here.

Dymond JS, Richardson SM, Coombes CE, Babatz T, Muller H, Annaluru N, Blake WJ, Schwerzmann JW, Dai J, Lindstrom DL, Boeke AC, Gottschling DE, Chandrasegaran S, Bader JS, & Boeke JD (2011). Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature PMID: 21918511

S.E. Gould About the Author: A biochemist with a love of microbiology, the Lab Rat enjoys exploring, reading about and writing about bacteria. Having finally managed to tear herself away from university, she now works for a small company in Cambridge where she turns data into manageable words and awesome graphs. Follow on Twitter @labratting.

The views expressed are those of the author and are not necessarily those of Scientific American.





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  1. 1. SacoHarry 8:21 am 09/19/2011

    That last sentence is what gets me. “The introduction of synthetic genes to make natural products…” The former, by definition, cannot lead to the latter!

    Link to this
  2. 2. S.E. Gould in reply to S.E. Gould 9:30 am 09/19/2011

    Thanks for your comment. Just to clarify that a little, by “natural products” I mean things like antibiotics, oils, vitamins and other compounds that are made in the natural world. By introducing synthetic DNA (i.e for enzymes not naturally found in yeast) these products can be synthesised inside the yeast. The synthetic genes code for non-yeast enzymes that make natural protein (or lipid-based) products.

    Hope that makes a bit more sense!

    Link to this
  3. 3. jgrosay 4:19 pm 09/19/2011

    The DNA inserted seems being just a synthetic copy of the one existant in nature. The true qualitative jump will be when somebody succeeds in the insertion of modifyed or improved shyntetic genes, coming from purposedly design, not from a Meccano-like activity as ordinary genetically modifyed organisms. Or are they doing it already ?

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  4. 4. S.E. Gould in reply to S.E. Gould 6:17 am 09/20/2011

    Certainly in bacteria people are designing new and improved genes and inserting them. A couple of summers ago I designed a gene for a purple pigment in bacteria by taking each gene from a system, modifying them to make them more effective in E. coli (the bacteria we were working with) and then putting them one after the other and inserting them all at once. Worked very well.

    Even in the system described in this post it wasn’t just an identical piece of DNA, but a designed one. The new DNA could be scrambled, allowing further research to be carried out. Normal yeast DNA can’t be scrambled like that – the DNA was purposefully designed for that ability.

    Link to this

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