By Brent Wells, PhD
An international team of scientists headed by a group at the New York University Medical Center has created the world’s first eukaryotic synthetic chromosome, meaning they have literally engineered life from its smallest units. Intrigued? You should be.
This work, recently published in the journal, Science, was achieved in the common budding yeast, Saccharomyces cerevisiae; the very same little fellow that makes your bread rise and your beer ferment.
A chromosome, in case you were wondering, is a continuous grouping of a subset of your genes. All 20,000+ human genes are spread across 23 distinct chromosomes while yeast genes, about 6,000 of them, are spread across 16. The goal of this study was to choose one of those naturally occurring yeast chromosomes and replace it with one synthesized, from scratch, in the lab.
How do you synthesize a chromosome? The answer is bit-by-bit-by-bit and with plenty of cheap help.
The group started with small, overlapping oligonucleotides, which are very short pieces of DNA – about 70 base pairs in this case. Next, you need an army of undergrads trying to earn an A grade in their Building-A-Genome class, and whose parents are unknowingly paying for your research, to stitch all of these small pieces together into increasingly larger fragments. This is what I imagine building a weave for Rapunzel would be like. Final assembly is completed in the yeast cell where the natural chromosome is replaced, one chunk at a time, with corresponding pieces of synthetic chromosome via a process called homologous recombination.
This was not, however, a Gus Van Sant-Psycho-shot-for-shot remake of the original. The chromosome lost a little weight in the process, trimming down to 272,817 base pairs from 316,617. Remarkably, the synthetic yeast were just as viable as the naturally occurring strain, suggesting that there’s a lot of useless DNA floating around in our cells. Among the discarded bits were regions of non-coding DNA called introns as well as transposons. Transposons are DNA sequences that can actually jump around the genome carrying other pieces of DNA with them and which are thought to be a major driving force in evolution.
Speaking of evolution, the group also engineered in sequences that would allow them to randomly alter the genome by taking out non-essential genes in a process they call SCRaMbLE-ing. The removal of these genes allows the team to look at the effects of variable-scale genome size reduction on viability. In other words, they can induce a genome ‘scramble’ in millions of yeast cells at once, which will remove different subsets of genes in each, and look at which genes are gone in the ones that survive. This mimics genetic deletion events that can happen naturally during evolution and will help us understand how evolution may occur and the pressures that can lead to the traits it eventually fixes. You can also really speed up a notoriously slow process.
This is not the first time a synthetic genome has been attempted, or completed. Groups have had success with viral and bacterial genomes in the past, but this is the first instance of something on this scale. Other groups are currently working on more of the 16 yeast chromosomes with the goal of eventually creating a completely synthetic yeast cell.
Beyond the potential to understand mechanisms of evolution and just see if we can actually do it, generation of synthetic organisms have far-reaching commercial potential. Synthetic yeast could be used to generate more efficient bio-fuels, rare medicines for Malaria and Hepatitis and more. And it would be cheap – at least in principle; did I mention they are calling these ‘designer’ chromosomes? I can only assume the synthetic strain was code-named Fendi or Prada.
So, should you be worried about ingesting some synthetic yeast during your next trip to Dunkin’ Donuts or Subway? Hardly. Scientists have engineered fail-safes into the synthetic chromosomes that make it impossible for the yeast to live outside of special conditions provided only in the lab. Of course, they did the same thing on Isla Nublar in Jurassic Park and anyone that’s seen Jurassic Park II knows that Jeff Goldblum nailed it when he demanded ‘Nature always finds a way’. But to those alarmist naysayers saying ‘What about the potential for environmental catastrophe?’ Let me offer this recompense: ‘What about the potential for better beer!’