A right-handed molecule can only copy left-handed ones.
by John Timmer – Oct 30 2014, 12:30pm CDT
Even the simplest forms of life, like bacteria, have a handedness, one that’s built into the chemicals they’re composed of. The complex, three-dimensional molecules that are essential to life can have the same exact set of atoms, yet be physically distinct—one the mirror image of the other. All the amino acids that life uses have a single orientation; same with all the sugars.
While life is very good at operating with this handedness, called chirality, nature isn’t. Most chemical reactions produce a mixture of left and right forms of molecules. This seemingly creates a problem for the origin of life—if both chiral forms were available, how did life pick just one? The problem is even more severe than that. If both forms are present, then the reactions that duplicate DNA and RNA molecules don’t work. And without those reactions, life won’t work.
Now, researchers have found this doesn’t pose much of a barrier at all. Through a little test-tube based evolution, they were able to make an RNA molecule that could copy other RNA molecules with the opposite chirality. In other words, they made a right hand that could only copy the left. But the duplicate, the left-handed form, could then readily copy the right-handed version. And as an added bonus, the new RNA molecule may be one of the most useful copying enzymes yet evolved.
The work was done by just two people, Jonathan Sczepanski and Gerald Joyce of the Scripps Institute. They were interested in the issue of chirality and set out to create an enzyme that could work with molecules that were the opposite chirality. Rather than try to figure out what structure might work, they chose an evolutionary approach, starting with a population of 1015 random RNA molecules and then putting them through several rounds of selection and mutation.
The molecule they wound up with is only 83 bases long. It’s made of right-handed RNA, and it only links together left-handed RNA molecules. When the researchers made a left-handed version of the RNA enzyme, the converse was true: it could only link together right-handed RNA. But the key thing is that it can perform these reactions even when there’s a random mixture of left- and right-handed molecules present. The apparent roadblock to life had been overcome in just 16 rounds of selection.
As a catalyst, it was also pretty good, accelerating the reactions it promotes by a factor of about 106. And it was indifferent to the length of the molecules it was copying, allowing it to link up molecules its own size or even longer.
But it also had one significant advantage over existing RNA-based copying enzymes. All of those were right-handed and copied right-handed RNAs. As such, a key part of their activity was base-pairing with the molecule they were copying. But left- and right-handed RNAs can’t base pair, so the new enzyme had to evolve a completely different way of sticking to RNAs. This means the enzyme is probably the most general one developed yet—it can operate on just about any RNA sequence.
Sczepanski and Joyce also point out that the enzyme is relatively young, only 16 generations away from a completely random sequence. With further evolution under different selective conditions, it could be possible to make this an extremely efficient and effective RNA copying enzyme.
The biggest impact of these results may be to cause a rethink about how we consider the origin of life. Many researchers have spent time trying to find ways that a mixture of chemicals could spontaneously segregate in ways that would allow chemistry to occur in a population of molecules dominated by a single chirality. It turns out that the exercise might not have been needed. "If early life did entail the cross-chiral polymerization of RNA," the authors conclude, "then there would have been an era when both sides of the mirror were indispensable."
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