We’re one step closer to self-sustaining chemical replicators, similar to what would have existed a few billion years ago, before true cells evolved. Lincoln and Joyce have created a couple of relatively simple molecules that assemble themselves from even simpler precursors in a test tube.
It’s not as straightforward as the simplest scheme one might imagine. The simplest model would be for a single enzyme, E, to catalyze its own assembly from two smaller precursors, A and B. This formula would lead to a test tube full of A and B to be quickly converted to a test tube full of nearly nothing but E with the introduction of a single copy of E. The actual solution is a little more difficult to explain.
In this case, enzyme E is built from precursors A’ and B’. Enzyme E does not catalyze its own construction, but that of enzyme E’, which is built from precursors A and B. So E catalyzes A + B → E’, and E’ catalyzes A’ + B’ → E. Got that? It ends up with the same result — E and E’ together quickly gobble up all the A, B, A’, and B’ in a test tube, producing a mixture of mostly E and E’. It’s diagramed here:
Those of you who are already familiar with Stuart Kauffman’s work will recognize this as an autocatalytic set, exactly the kind of thing he predicted would be an early chemical precursor to life. It’s also the simplest kind of autocatalytic set, with only a pair of elements working together; there’s nothing to say there couldn’t be three interlocking cycles, or four, or a hundred, instead of just two. It’s darned cool.
Now you might be saying, “But these are designed enzymes, created by a couple of intelligent scientists!” Not quite. They started with a very rough sequence, one that inefficiently catalyzed an A + B → E sort of reaction, but that not only worked slowly, but also produced faulty products that eventually killed the reaction after a few cycles. Then they tweaked it to form a minus-strand enzyme, and then they subjected both the plus and minus strand forms to — natural selection! They made copies with mutagenic PCR (so they had a range of random variants), ran it through several cycles of in vitro selection for more efficient forms, and ended up with two RNA enzymes that were good at building copies of each other.
Here are the actual RNA sequences of the two enzymes.
I can imagine the next objection: those are fairly long strings of nucleotides, and the precursors are fairly complex oligonucleotides, too. The point, however, is that it is a more complex enzyme built up from simpler precursors. No one is pretending this is an example of the earliest chemical reactions — it’s more like a proof of concept of the idea.
Another cool thing about this experiment is that the enzymes proved to be efficient and robust. Below, you can see that they acheived exponential growth, only leveling out when the substrates were exhausted.
These enzymes worked well. If they were producing deleterious byproducts that were interfering with the reaction, you’d expect to see a gradual decline in the rate that was independent of the reduction in concentration of the substrates; no such effect was observed in the experiment below, where substrates were regularly replenished. These paired chemical replicators were just cruising, reliably making lots of copies of themselves, and they could keep going for ages…like, 4 billion years.
Again, don’t have illusions that this is an example of a resurrected chemical function from the dawn of time — it’s a demonstration of the feasibility of one part of the process of chemical evolution. The authors also mention another interesting feature of the work in their conclusion.
Ultimately the system should provide open-ended
opportunities for discovering novel function, something that
likely has not occurred on Earth since the time of the RNA
world, but presents an increasingly tangible research
People often wonder why these kinds of prebiotic reactions aren’t going on all the time in the world around us, and the authors agree that this is not something that can occur naturally right now. Why? The answer is simple: the world around us is swarming with the ravenous, finely-honed products of billions of years of evolution, creatures like bacteria, that would readily swoop down on any accumulation of nucleotides and consume them before these kinds of reactions could even start. Nowadays, it takes a sterile lab and many precautions to put these chemicals into the kind of coddled environment where they can evolve.
Lincoln TA, Joyce GF (2009) Self-sustained replication of an RNA enzyme. Science Jan 8. [Epub ahead of print].