Mar 28 2014

Synthetic Yeast

Synthetic biology is an emerging field with incredible potential. The idea is to build genomes from the ground up. Craig Venter made the first breakthrough in synthetic biology four years ago when his team created the first artificial bacterial genome. Now another team has made similar progress with yeast, which is eukaryotic (meaning the cells keep their DNA in a nucleus).

To be clear, these teams have not made life entirely from scratch, not even the genome. In Venter’s case he started with an existing bacterium, and then recreated its genome with some changes, and inserted it into a bacterium whose DNA had been removed.

In the latest research, the scientists have created one of the yeast’s 16 chromosomes. Again, they did not build it from scratch but started with the wild chromosome and then made significant changes. They therefore have 15 chromosomes to go, but there is no reason they should not get there.

Some argue that this is not really artificial life, and they have a point- but this is just a semantic argument. They have gone beyond inserting or deleting single gene to making massive changes to the genome, or in this case to a single chromosome. At what point something becomes “artificial” is a bit arbitrary.

In any case, the technology is potentially very powerful. The research that has been done so far is an important proof of concept. What the latest study shows is that a significantly altered chromosome can be added to a yeast cell and the yeast will survive and even reproduce. The new chromosome seems to work fine.

One significant aspect of the changes they made is this:

The new chromosome, known as SynIII, involved designing and creating 273,871 base pairs of DNA – fewer than the 316,667 pairs in the original chromosome.

The researchers removed huge chunks of DNA that they deemed “junk.” There is somewhat of a controversy over whether or not junk DNA (DNA that does not code for proteins or serve a known regulatory function) is truly inactive or unnecessary, or if it simply has unknown regulatory functions.  The ultimate test of this question is to remove apparent junk DNA and see what happens. If this early experience with yeast holds true in later research, it would strongly suggest that junk DNA is truly junk.

The obvious practical application of this technology once it sufficiently develops is bioengineering life forms to perform industrial tasks. Yeast is a good target because it is used in many industries already (brewing and baking). Yeast species could theoretically be engineered to manufacture medicines and vaccines, biofuels, plastics, and other material.

Cells are living factories, and they can potentially be harnessed for mass production.

Of course, all revolutionary technology will create some anxiety. In a 2012 survey one third of Americans indicated that they felt synthetic life should be banned until it is better understood. Surveys are tricky, but at least it indicates there is some anxiety out there about synthetic life.

Any new technology with the potential for great benefits is likely to also have the potential for abuse and great harm. This technology can be used to create biological weapons, for example. There is also the issue of unintended consequences.

None of this, in my opinion, is a reason not to move forward. Partly we can just let the science sort itself out. If regulations are needed to reduce the risk of abuse or accident, that does not seem like an extreme challenge.

We are likely still years away from practical applications of this technology, but it seems to be moving forward nicely.


19 responses so far

19 Responses to “Synthetic Yeast”

  1. ca1879on 28 Mar 2014 at 9:49 am

    I’m fine with all of this – up to the point where the lead researcher starts shopping for high voltage gear and a secluded castle.

  2. Flailon 28 Mar 2014 at 10:36 am

    I have a question for folks that have a better grasp of the biology and genetics involved with this. I feel like I know just enough about this stuff to ask silly questions, so hopefully someone has a non-silly answer for me.

    I know that brewers often have to monitor the random mutations in yeast over generations, because they can alter the flavor of the beers they produce. Would removing vast swaths of this “junk” DNA make any progress to reducing these random genetic mutations, or would it make the mutations “worse” in that they would occur solely in the “non-junk” portions of the DNA that remained?

  3. Bronze Dogon 28 Mar 2014 at 1:59 pm

    @Flail: I’m a layman when it comes to biology, but as I understand it, junk DNA’s de facto purpose is essentially a buffer to limit mutations to functional genes. So I’d be more worried a junkless genome would have a greater risk of getting broken in some way or another unless they can lower the mutation rate.

    A while back, I had an idea for a mech game (more like remote controlled & AI robot infantry than the huge mechs, really) where I was trying to go for some level of realism, and one thing I had in mind was engineered bacteria that produce biodiesel to power the robots and/or their chargers.

  4. Heptronon 28 Mar 2014 at 10:08 pm

    I am inclined to agree with Bronze Dog about the Junk DNA thing. My understanding (not knowing tons about genetic engineering) was that the junk DNA could serve as a sort of back-up in case there’s a copy error. It seems to me that removing the junk DNA and then having a copy error would potentially render the yeast useless.

    As an aside, biotech is awesome! I got my master’s degree in Biochemical Engineering working on bioproduction of succinic acid. Typical production of succinic acid starts with the partial oxidation of butane to form maleic anhydride. This reaction requires strict control of the oxygen in the system so it doesn’t blow up, and the reaction takes place at a around 150°C and 2atm.
    Bioproduction of succinic acid uses bacteria at 37°C and 1atm.
    There’s even a bio-succinic acid plant under construction in my city, so hopefully it’s on it’s way.

  5. BillyJoe7on 29 Mar 2014 at 12:45 am

    Bronze Dog & Heptron,

    One could argue that “junk DNA” that does something is not junk DNA.

    Removing the “junk DNA” from the artificially created chromosome produced a normal replicating yeast. Therefore it could be concluded that the “junk DNA” they removed really is junk DNA. Of course they would need to study a large number of generations to be certain that the junk DNA was never used to replace damaged DNA.

  6. tmac57on 29 Mar 2014 at 12:20 pm

    It’s more than a little unsettling to me how easy it has become to perform bioengineering experiments by even rank amateurs and kitchen chemists,who are not required to exercise the safety standards that academic and industry labs must follow. The potential benefits for this kind of research seem almost unlimited,but the risks are also quite large. Maybe we are being too careless with the way this technology is being rolled out. It may already be too late to do anything about it now though because the information is already out there.

  7. etatroon 30 Mar 2014 at 1:37 am

    I have always envisioned “junk” DNA as being selectively advantageous because it serves as a basis for genetic diversity and increases the rate at which changes in body plan, increases in complexity, and creation of new niches. For example, a particular gene is duplicated but serves no function, it persists because there’s no cost to carrying it along … then a transcription factor site, a translation start site, or a DNA demethylation or something happens, and the duplicated gene … which may have undergone some mutation at a background rate starts to be translated to a protein, and perform some function similar to, but not exactly the same as it’s ancestor. This could have a deleterious or positive effect on the organism’s survival. It could be in a part of he genome that causes it to function in a specific cell, tissue, or time of development. Expanding the combinatorial possibilities would have an advantage to carrying along the DNA. As Steve has mentioned before, we only think it’s “junk” because we don’t Yet know what it does. The DNA exceeding the bare minimum for survival of an individual is not necessarily carrying along “junk”, but rather, keeping a (selected for) reservoir (for lack of a better term) of diversity.

  8. etatroon 30 Mar 2014 at 1:47 am

    TMAC, is there any particular reason that you consider New York University Medical Center’s Institute for Systems Genetic to be rank amateurs and kitchen sink chemists?

  9. BillyJoe7on 30 Mar 2014 at 2:32 am


    Your first and second sentences appear to be in conflict:

    “I have always envisioned “junk” DNA as being selectively advantageous”
    “it persists because there’s no cost to carrying it along”

    As do your first and third sentences”

    “I have always envisioned “junk” DNA as being selectively advantageous”
    “This could have a deleterious or positive effect on the organism’s survival”

  10. BillyJoe7on 30 Mar 2014 at 2:51 am

    And this bit:

    “The DNA exceeding the bare minimum for survival of an individual is not necessarily carrying along “junk”, but rather, keeping a (selected for) reservoir (for lack of a better term) of diversity”

    I’m not sure how an organism can select for DNA that does nothing. I suppose if there was a mutation that caused an organism to eject “junk” DNA that mutation would be selected against, but I can’t see how DNA that does nothing can be selected for – while it is doing nothing. If cannot be selected for because of some function it might perform in the future.

    Oh, and this:

    “there’s no cost to carrying it along”

    I’m not sure this is correct either. Imagine if 99% of the DNA was junk DNA. This has to be replicated in every cell in the body. This surely would incur some cost. It seems to me that, despite the cost of carrying it along, there is no mechanism for ejecting it and, therefore, it gets carried along to fortuitously serve some purpose in the future.

  11. Draalon 30 Mar 2014 at 11:29 am

    If there are any in-depth questions regarding genetically engineering yeast I can field them. The yeast artificial chromosome project has been ongoing for at least the last 6-10 years (look up Saccharomyces cerevisae v2.0 project). The methods they use are based on well establish procedures.

    “I know that brewers often have to monitor the random mutations in yeast over generations, because they can alter the flavor of the beers they produce. Would removing vast swaths of this “junk” DNA make any progress to reducing these random genetic mutations, or would it make the mutations “worse” in that they would occur solely in the “non-junk” portions of the DNA that remained?”

    Genetic drift is a well known issue in brewing beer. It has been occurring ever since man has realized the use of yeast in alcohol fermentation. Selection pressures like temp, wort content, flocculation, attenuation, alcohol tolerance, etc. have evolved S cerevisiae into the hundreds of strains that are used today for. For a more detailed explanation, read Chris White’s book “Yeast”, (he’s the head biologist and founder at White Labs).
    Brewers usually ‘repitch’ yeast from a previous fermentation (collecting yeast is called cropping, either top or bottom cropping) into a new fermentation to achieve consistent results and save money. However, overtime mutations accumulate and can alter the quality of the beer. A limit is often set for how many times the yeast is repitched, depends on the brewer (~15 times; the record is something like 300+). One reason that the yeast mutate so frequently is because these industrial strains are polyploids, that is they have multiple copies of each chromosome (often 7 copies or greater). Yeast has also an INCREDIBLE ability to undergo homologous recombination, either with itself (eg., DNA repair) or during mating (yes, yeast has ‘genders’); chromosomes exchange parts during meiosis.
    Brewer’s address this issue through a number of ways. Yeast can be stored in freezers for many many years; an original batch can be split up and used to inoculate cultures for years to come. Yeast can be re-isolated as single colonies and several colonies can be tests simultaneously to identify the ‘best’ strain and junk the rest. Yeast can be grown in defined culture conditions that would favor a preferred phenotype (like fastest growers) before addition to the fermentor.

    Laboratory strains are more stable genetically. They are often maintained as haploids (single copy of each chromosome) which basically eliminated the ability for genetic drift due to homologous recombination between copies of nearly identical chromosomes. Same as in industry, strains are frozen for long term storage and single colony isolation procedures are common. Additionally, DNA repair enzymes can be targeted to further decrease the ability of the yeast to undergo recombination. DNA sequencing tools are available to verify genome sequences.

    Example of homologous recombination (O = native sequence, X = mutation)
    Parental gene 1: OOOXOOOOOOOOOOOOO
    Parental gene 2: OOOOOOOOOOOXOOOOO

  12. Draalon 30 Mar 2014 at 11:44 am

    So to answer the original question…
    Maybe. However, it could go the other way. The ‘junk’ DNA may provide unknown functions.

    Other more immediate considerations is the cost associated with engineering a yeast brewing strain. For one, it would cost a moderate amount to have a proper bio lab running in the brewery (all the big guys do). Engineered strains would likely require FDA approval (huge barrier in time and money). Just as important or more so, it would get the GMO label. Beer makers know that GMO’s are not popular and they would be make a huge gamble in selling a GMO beer. (the irony is the yeast are highly genetically modified organisms resulting from thousands of years of selection).

  13. etatroon 30 Mar 2014 at 3:17 pm

    BillyJ – I think you misunderstood me. You put together sentences and said they conflict, conflating the meaning. Anyhow. An organism doesn’t select, the environment does. I didn’t write this to start an argument, but share my understanding of it. What I meant was there is an advantage to having a bunch of DNA as a reservoir for generating diversity. My understanding also is the most of the “junk” DNA is retrotransposons, replicating and moving around chunks of the genome; duplicating whole genes (into pseudogenes) and piecing together genetic modules with structural and regulatory elements; if it becomes translated and has a deleterious effect (say, the organism dies), then that particular combination of modules doesn’t work; if it becomes translated and has a beneficial effect, well ….

    This works both ways, though. It is also true that some species have “devolved,” meaning that they are simpler than their ancestors (in both body plan and genes); I think this happens more frequently with parasites. I think an example would be an ancestral roundworm that lived before mammals; the roundworm parasites that inhabit mammals are simpler than their ancestors that inhabited ponds & dirt.

    I read somewhere that if an alien all of the life on Earth, stuck it in a blender, and analyzed the DNA, they would conclude that the major replicating entity on Earth were retrotransposons.

  14. tmac57on 30 Mar 2014 at 7:34 pm

    etatro- I didn’t mean to give the impression that I was worrying about the New York University research group. There are amateur groups known as Bio-hackers who,similar to the early computer hacker groups,are entering the field because of intellectual curiosity,or maybe because of the inability to do research at a company or university or whatever.They probably are well meaning and educated (maybe geeky) and curious scientists or wanna be scientists that group source and probe biological and genetic engineering frontiers,and might be the next Steve Jobs if lucky.But they also might be the equivalent of the most notorious of the computer hackers of our age.

    Here is a NYT article about a more benign group of ‘home brew’ aspiring bioengineers :

    It doesn’t take too much imagination to see what might go wrong here.

    Oh,and the last couple of years has shown that even high level bioengineering labs can pose troubling questions about their work and publishing the methods for modifying a couple of flu strains.

  15. BillyJoe7on 31 Mar 2014 at 6:33 am


    Yes, an unfortunate slip of the tongue.
    The environment selects the beneficial mutations.

    But my point was that the environment cannot select for DNA that does nothing. It cannot select for junk DNA. It cannot look forward and see that it might come in useful in the future. However, as you seem to be suggesting in your response, the so called junk DNA is not really junk DNA. Most of what is called junk DNA actually does do something and therefore can be selected for (by the environment!)

    And, yes, I was not arguing either, just clarifying.

  16. Flailon 31 Mar 2014 at 9:50 am


    Thank you so much for your response. Your explanation of homologous recombination makes sense.. I never realized yeast are so complicated.

    I hadn’t thought about the GMO label and all of the regulatory rigmarole that would be required to use modified yeast in brewing. Fascinating stuff!

  17. Steven Novellaon 31 Mar 2014 at 1:01 pm

    To clarify – junk DNA is not determined solely by a lack of a known function. Scientists also determine if there is any selective pressure on the DNA sequence by seeing if it is drifting along with the background mutation rate or if any sequences are conserved through selective pressure. If there is zero apparent selective pressure, that is also consistent with the DNA being junk.

    Theoretically, selective pressures could favor DNA regulatory mechanisms that allow junk to hang around, without selecting for any particular sequences within the junk.

  18. etatroon 31 Mar 2014 at 5:09 pm

    Theoretically, selective pressures could favor DNA regulatory mechanisms that allow junk to hang around, without selecting for any particular sequences within the junk.
    That’s what I meant, thanks for finding meh words. I think we will find (if we look … maybe it’s been done) the selective pressures favoring DNA reg. mechanisms that allow junk DNA to hang around happen for K-selected species. I think I learned about “junk DNA” and retrotransposons / gene duplication stuff in freshman biology and it totally blew my imagination away.

    As far as mechanisms for expelling DNA, since we’ve been observing it, it happens all the time in humans during meiosis, it just happens to lead to disease states. Isn’t that the origin of the Y chromosome? A “degenerate” X-chromosome …. it sticks around because it has the SRY gene that leads to maleness. One could argue the whole chromosome is just a vector for the SRY gene. Or the existential question: is my whole life just a vector for the SRY gene?

  19. SteveAon 01 Apr 2014 at 7:40 am

    Flail: “I know that brewers often have to monitor the random mutations in yeast over generations, because they can alter the flavor of the beers they produce. Would removing vast swaths of this “junk” DNA make any progress to reducing these random genetic mutations, or would it make the mutations “worse” in that they would occur solely in the “non-junk” portions of the DNA that remained?”

    If you stuck 1,000 ballons in a field, and 800 of the ballons were black (representing junk DNA) and 200 white (representing the good stuff), and if you then threw in a couple of handfuls of darts (mutations), then the chances of any of the white balloons being hit would stay the same regardless of how many black balloons you took away or added.

    Assuming this is a decent anology, the aswer to your question is that it would make no difference.

Trackback URI | Comments RSS

Leave a Reply

You must be logged in to post a comment.