Genome Transplantation - Coming to a Bacteria Bacterium Near You

Well, I was interviewed yesterday by the AP (see the AP article here) relating to an article in Science on Genome Transplantation by John Glass, Craig Venter, and crew and the Venter Institute. Their article is coming out in tomorrow's Science. Though this was not published in an Open Access journal, I think this one is definitely worth talking about and looking at.

Here is what they did, in a nutshell. Took one mycosplasma species (mycoplasma are bacteria that do not have cell walls and have very small genomes) and very carefully removed its chromosome. They then mixed this with a recipient mycoplasma that had some detectable genetic differences. And they then selected for cells that had a antibiotic resistance function found only in the "donor" genome. And they got some growth. And surprisingly, many of the cells that grew up appear to have COMPLETELY replaced the endogenous genome with the donor genome. Thus they use the term genome transplantation.

It seems like a pretty solid paper, although I still am not 100% convinced that these are not some relics of the original donor cells that simply made it through the genome extraction processes intact (this is very unlikely given their controls but still possible). Assuming that they really have genome transplantation, it is a pretty cool result.

Why? Well, it means that at least in some sense, they can use this as a tool in synthetic genomics. One of the big limitations of synthetic biology right now is how one would make a genome in vitro of a bacteria and then get this genome to "boot up" into a cell. For viruses, they can make genomes in the test tube and get the virus to be created because viruses are cellular parasites and all they have to do is get the DNA for the virus to be packaged in the right way into a cell or viral capsid. But for a bacteria, things are much different. The challenge has been how to get a recipient cell to boot up a new genome and delete its own or at least silence its own. And without going into all the gory details, this has proven challenging.

So - now genome transplantation. On the one hand, it can serve as a way to boot up a new genome. However, it probably has limited potential in many ways since to get the new genome to effectively replace the old one, it has to not only be replicated, but the machinery of the cell present in the recipient has to work well enough on all the key components of the donor genome to get the booting up to work. For example, all the promoters in the donor genome must be transcribed efficiently by the recipients machinery, at least for the RNA and protein synthesis machinery genes, so that the donor stuff can get made. And of course the replication origin and other replication features must all work as well. What this means is that I think genome transplantation will only work if the donor and recipient are very similar to each other for most of the housekeeping genes and functions. So this is not yet ready to work for all of synthetic biology. But it still seems pretty cool.