Scrambled Yeast: Breakthrough or Just More Hype?

Posted by Emily Beitiks September 15, 2011
Biopolitical Times
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An article in Nature this week describes the successful synthesis of DNA, producing a new “arm” to a yeast chromosome through a process called “scrambling.” Because this research was conducted on yeast, which have more complex chromosomes than those previously synthesized, the NSF suggests that this is “a significant advancement for the field of synthetic biology.” 

The NSF press release describes the scrambling process this way:

...the synthesized DNA in the arm was "scrambled;" this process involved adding a chemical to the yeast culture that caused major changes to gene-sized blocks of nucleotides in the synthesized DNA. By scrambling, some genes were lost and the order of other genes was shuffled.

This entire process was then repeated in various yeast cultures to produce a multitude of modified arms--just as shuffling and randomly removing cards from multiple decks would produce a multitude of different decks. Because of resulting differences in the scrambled genetic codes of the yeast cultures, these cultures displayed trait differences.

"We were able to track the changes we made relative to the native yeast and isolate scrambled derivatives from the semi-synthetic yeast," said Boeke. "We thereby generated a wide range of different derivatives from the semi-synthetic strain. Some scrambled strains grew as well as the native yeast and some did not." Such variation yielded insights into the relationships between DNA structure and trait expression in yeast.”

But is this achievement really as noteworthy as they suggest? Some scientists who follow developments in synthetic biology closely would say “no.” Professor of Cell Biology and Anatomy Stuart Newman responds to the above passage and shares his doubts:

This is a perfect illustration of the fact that almost nothing is known about the relation of a genome to a complex phenotype. (This is not the same thing as the relation of a gene to a protein sequence – a lot of this is understood). Here is an abstract of a paper from a few years ago on scrambling gene regulation in E. coli. The degree to which it made no difference to the phenotype was amazing: http://www.ncbi.nlm.nih.gov/pubmed/18421347

In other words, changes at the genome level that you would expect to be significant sometimes make remarkably little difference to the way the organism develops. The alluring notion that synthetic biology "breakthroughs" will soon enable us to rebuild genomes to desired phenotypic ends seems to be out of sync with the true state of our knowledge. Readers/buyers/believers beware.

Newman’s conclusion:

The bottom line is that there is no theory behind synthetic biology. It’s just boys with toys.

Previously on Biopolitical Times: