A tiny scrap of the genetic molecule RNA can *almost* copy itself.

This is a hyper-abridged TLDR because I had a totally different post scheduled to run, but the researchers behind the study ended up having a delay posting their work and I didn't want to break their embargo. And then I had to fly home from a training in Brussels, so I just sat down to write this at 10:50 pm.

So I now present for your enjoyment the unproofread residue at the bottom of my brain juice barrel: a quick note on a cool study about a surprisingly small molecule that can almost copy itself and what it could mean for the origins of life.

What happened

Researchers synthesized a tiny strip of RNA (DNA's single-stranded cousin) that can make copies of other strips of RNA — including itself, if it is provided the right template. RNA molecules are like long "words" made by chaining four different molecular "letters" together, and this molecule is just 45 letters long. Other molecules that can do similar jobs are 150-300 letters long.

Who did it

This study was led by Edoardo Gianni, a postdoc in Philipp Holliger's group at the MRC Laboratory of Molecular Biology in the UK which studies artificial DNA and RNA to investigate the origin of life. The one outside co-author, theoretical biologist Enrico S. Colizzi at the Inria Centre de Lyon in France, contributed a theoretical model of self-replicating molecules discussed briefly in the paper.

How they did it

The team synthesized pools of random RNA sequences and screened them for the ability to copy RNA strands, and then iterated on the best (and smallest) molecular copy machines. They basically ran evolution in a lab, leading to a very tiny strip of RNA-copying RNA they dubbed QT-45. Cute.

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Why it matters

RNA is a big deal in the origin of life. That's because it can both 1) store genetic information like DNA and 2) catalyze chemical reactions like proteins. In 1989, researchers found an RNA molecule could copy RNA from template strands. It was derived from natural RNA-enzymes (called ribozymes) that were tweaked to achieve RNA-copying activity.

Since then, that ribozyme and its descendants have basically been the only game in RNA-copying RNA town. This new study produced a totally new lineage of self-replicating ribozymes that was much smaller than previously described ribozymes.

Not only that, it can also copy both itself and its "template" strand, which is like the mirror reflection of an RNA word. An RNA-copying enzyme uses the mirror template to reconstruct the original strand. That means, in theory, something like QT-45 could copy itself — it could copy its own template from itself, and then copy itself from its template. No other previous RNA-copying RNA could do that.

But there's a catch: QT-45 isn't very good at its job and stops working before this true self-copying can happen, study author Edoardo Gianni told me via email:

 This is not quite self-replication yet (sorry to be pedantic but my colleagues would be very upset if I claimed self-replication already), as we don’t first make the template and then use the template to make a new copy of the ribozyme. The yields are also minimal, meaning that the current system would not sustain itself and would decay over time (tho we are working to improve it to reach this point). 

What I think

Broadly speaking there are two camps in the origin of life field. There are the information-first folks, who tend to like warm little ponds and the RNA world, and there are the metabolism-first folks, who tend to like hydrothermal vents and see life as self-sustaining networks of chemical reactions. This might seem like a win for team RNA-world, but I'd be cautious before interpreting it that way. Life needs genetic material eventually however you start it.

But I do think this finding tells us something about life's origin. That a short, random RNA sequence could evolve the ability to copy RNA on a human timescale — not in gzhillions of years — is significant. It tells us that self-replication isn't really that mysterious. It can be "stumbled upon." And that makes life sound a little less miraculous and a little more inevitable.

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