The New Genome on the Block

The world is abuzz with the announcement by Craig Venter and colleaguesthat they have successfully booted up a synthetic bacterial genome.

I need to really read the paper but I have skimmed it and spotted a few things. For example, this is a really impressive feat of gene synthesis but even so a mutation slipped in which went unnoticed until one version was tested. Even bugs need debuggers!

It is also a small but important step. Describing it as a man-made organism is in some ways true and some ways not. In particular, any die-hard vitalists (which nobody will admit to being, though there are clearly huge number of health food products sold using vitalist claims) will point out that there was never a time when there wasn't a living cell -- the new genome was started up within an old one.

It is fun to speculate about possible next directions. For example, they booted a new Mycoplasma genome within another Mycoplasma cell -- different species, but very similar to the host. Clearly one research direction will be to try to create increasingly different genomes. A related one is to try to bolt on entire new subsystems. A Japanese group tried fusing B.subtilis (a heavily studied soil bug) with a cyanobacterium to see if they could build a hybrid which retained the photosynthetic capabilities of the cyano; alas they got only sickly hybrids that didn't do much of interest. Could you add in photosynthesis to the new bug? Or a bacterial flagellum? Or some other really complex more-than-just-coupled-enzymes subsystem?

But as someone with a computer background -- and someone who has thought off-and-on about this topic since graduate school (mostly off, to be honest), to me a really interesting demonstration would be a dual-boot genome. Again, in this case the two bacterial species were very similar, so their major operational signals are the same. Consider two of the most important systems which do vary widely from bacterial clade to clade (the genetic code is, of course, near universal -- though Mycoplasma do have an idiosyncratic variation on the code): promoters and ribosome binding sites. Could you build the second genome to use a completely incompatible set of one of these (later both) and successfully boot it? Clearly what you would need is for the host genome -- or an auxillary plasmid -- to supply the necessary factors. Probably the easier one would be to have the synthetic genome use the ribosomal signals of the host but a different promoter scheme. In theory just expressing the sigma factor for those promoters would be sufficient -- but would it be? To me this would be a fascinating exercise!

Now, I did claim dual-boot. A true dual-boot system could use both. That is much trickier, but particularly on the transcriptional side it is somewhat plausible -- just arrange the two promoters in tandem. Ribosome binding sites would need to be hybrids, which isn't as striking a change.

There are even more outlandish proposals floating out there -- synthetic bugs with very different genetic codes (perhaps even non-triplet codes) or the ultimate synthetic beast -- one with the reverse handedness to all its chiral molecules. Those are clearly a long ways off, but today's announcement is another step in these directions.