We are the only life we know. We have 20 canonical amino acids, 5 canonical nucleotides, and we relate the two via a genetic code where the exceptions prove the rule of its common origin. Boring.

But effective. Life is parsimonious because evolution is parsimonious. Shortest path to best fitness wins. In a fitness landscape that has foothills undulating up into mountains, that’s great. In a landscape where there is a distant Olympus, though, rising starkly from the plains, not so much.

This is where we come in. We are at a stage in our evolution where we can control evolution. How cool is that? And not on the bazillion year scale where organisms make oxygen which makes new organisms. No, we can begin to change the base set of chemistry right now.

I’ve been fascinated by this all my career, ever since I was a graduate student and read the coolest-paper-you’ve-never-heard-about: “Membership mutation of the genetic code: loss of fitness by tryptophan” (Wong (1983), PNAS, 80:6303; note to Jeff, you still need better PR!). This paper describes the evolution of the unSubtilis, a strain that can use 4-fluorotryptophan in place of tryptophan throughout its entire proteome. That’s right, a completely unnatural organism. At first I believed this result must just be wrong, but when I got my own lab I got the Wong strain, and we proved to our own satisfaction that it in fact grew well with only 4fW in the medium. We then tried to make an unColi of our own, but without the same type of success (Bacher and Ellington (2001), J Bact, 183:5414). Still, new chemistries are not evolutionarily inaccessible. Mostly they get adopted piecemeal (see selenocysteine or pyrrolysine for details), but it is possible to get them adopted whole hog.

What else can be done? Folks in the past have accommodated bacteria to heavy water; I heard a very interesting talk from Felisha Wolfe-Simon at the Geobiology meeting I was at about organisms that grow in high arsenic; and there are a few odd species on the planet that can incorporate fluorine into amino acids (although primarily for making natural products; I don’t think they go into proteins … yet).

Given the genomics revolution that is occurring (both sequencing and synthesis) the stage is set for organismal augmentation, for changing the base chemistry of life. Undoubtedly George Church amongst others will have something to say about this. But the real fun will be finding out what life does with its augmentation. I have no idea what new functionalities an organism that has fluoroproteins or As-DNA will come up with. But this will shift NeoLife to a Whole. Nother. Level. of the fitness landscape where it can slip and slide around.

-- originally posted on Thursday, July 1st, 2010