February 06, 2008

"New life" pt. 2 and the minimal genome

ResearchBlogging.orgIn my last post I discussed why "new" or "man-made" life wouldn't really be all that new and I ended with the suggestion that the road towards making "new" synthetic life might be a goal all in itself. I would like to elaborate a little bit on that and then write something about why Mycoplasma genitalium is so interesting in this respect.

The end of creating "synthetic organisms" (a term used loosely) would be something like "engineered" bacteria that would produce specific substances or maybe even catalyze particularly interesting biochemical reactions. This is not that different from what we're already capable of doing, granted it would be in a larger scale. Putting synthesized DNA, especially designed for a purpose, into living cells and having them express that DNA is common practice in molecular biology, even though it has its limitations. You can buy the cells from catalogs and the whole process is carried out with ready-made kits by just following the instructions in the box.

The strength of producing "synthetic organisms" would be that you could create entire systems and not just get the bacterium to produce one or a few substances. You could design the biochemical cellular environment of that organism on a larger scale and gear it towards one preset goal. This is because theoretically you could control every aspect of that organism's genome: not only everything that the cell produces but also how it regulates itself. But the key thing to look out for here is "every aspect". We are still far away from having a complete understanding of how genomes are made up. So a scenario where we have absolute control of an organism's biochemical processes seems far ahead in the future - another reason why the headlines of "new" or "man-made" life are exaggerations - but getting there we will undoubtedly have to learn more about how evolution has built genomes and what exactly is needed to constitute a functioning genome. A very exciting prospect.

It's in this regard that Mycoplasma genitalium is important. It has the smallest known genome of any self-replicating organism and it's one of the simplest free-living bacteria there are. It only has 482 protein-coding genes, compared to us humans' approx. 20,000 (at the last count). In 1995 it became the second genome to be sequenced for this reason and no doubt this is what makes it such a good candidate to be the stepping stone towards the creation of a "synthetic" organism. By looking at Mycoplasma we can deduce what the minimal requirements are for a genome to work: how many genes are necessary for sustaining life?

At the last count in Mycoplasma genitalium from 2006, 387 out of 482 protein-coding genes and 43 structural RNA genes are essential for the growth of this bacterium. This was deduced by mutating gene after gene, making them useless one after the other, and seeing whether or not the mutant bacteria could live and grow. The real interesting number though, is 110. 110 of the 387 essential genes still have unknown function. The genes have been identified in the DNA, but it's still unknown what they do or what hypothetical proteins are produced from them.

So we're not yet in a time where we know every aspect of what an organism does, not even one of the simplest ones, and we're not yet in a time where we can design an entire viable genome in our interest and thus control every aspect of an organisms biochemical processes, or in other words, "play god".

If or when that day comes, there's no doubt that many exciting and useful applications will be available to us. But let's not forget that during the process we will have acquired a wealth of knowledge about ourselves and indeed life itself that will be difficult to overestimate. Then the answer to the question whether or not we should "create life" (again, using the term very loosely) just because we can, gains a whole new dimension.

Glass, J.I. (2006). Essential genes of a minimal bacterium. Proceedings of the National Academy of Sciences, 103(2), 425-430. DOI: 10.1073/pnas.0510013103

Gibson, D.G., Benders, G.A., Andrews-Pfannkoch, C., Denisova, E.A., Baden-Tillson, H., Zaveri, J., Stockwell, T.B., Brownley, A., Thomas, D.W., Algire, M.A., Merryman, C., Young, L., Noskov, V.N., Glass, J.I., Venter, J.C., Hutchison, C.A., Smith, H.O. (2008). Complete Chemical Synthesis, Assembly, and Cloning of a Mycoplasma genitalium Genome. Science DOI: 10.1126/science.1151721

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