Today you get to meet yet another of my random interests: the origin of life. (Is there a person with an interest in living things who isn’t fascinated by the origin of life?) And, since we sciencey types are very anxious about personal biases, I might as well start with a confession.
I love the RNA world hypothesis.
It was just one of those things that you learn at school/uni (I think it was 1st year molecular biology for me), and it’s so neat and elegant and compelling that you immediately fall in love. Sure, later, when you’re out of the inevitable simplicity of class, you learn about the nuances. The difficulties. But the evidence for still seems so convincing that you have no doubt that we’ll eventually solve the problems.
In case you aren’t familiar with it, the RNA world hypothesis is the leading solution to the chicken and egg problem that is the “central dogma” of molecular biology (diagram from Wikipedia):
DNA is great genetic hardware, but it’s nothing without proteins. Proteins are encoded in DNA, but the code is useless without proteins to read it. Making DNA requires proteins. But the proteins come from the DNA code. You see where this is going…
RNA takes the stage
The RNA world is an ingenious idea that elevates RNA from being merely the messenger between DNA and protein to centre stage. While its big brother DNA is a fairly stable and inert molecule, RNA is much more chemically active. It doesn’t like languishing in long, stable double helices – rather, it folds up into all kinds of odd shapes that can, surprisingly, catalyse a variety of chemical reactions. Just like proteins. Yet the “letters” of RNA can form complementary pairs, allowing for faithful copying. Just like DNA.
And, so the theory goes, there was a time when RNA was both the genome and the enzymes (enzymes made of RNA are called ribozymes). The right sort of RNA molecule could have copied itself without proteins , and performed whatever chemistry a primitive life form needed – also without proteins. Crucially, the right sort of RNA molecule could have invented proteins .
One of the key revelations to lend support to the RNA world hypothesis is that proteins in cells today are still made by RNA. Proteins are manufactured in ribosomes. A modern ribosome is a very complicated structure made of several folded-up RNA molecules and dozens of proteins. However, investigations of its structure (see Cech  for a quick review) revealed that the place where amino acids are joined into a protein chain is all RNA – the proteins may support the RNA, but it seems to be the RNA that actually does the job.
Beautiful hypothesis vs. ugly facts?
So, everything is shiny and awesome and exciting. Ribozymes capable of all sorts of interesting chemistry  abound, and we have some very neat ideas regarding how RNA paved the way towards the modern protein-and-DNA world .
And then Harish and Caetano-Anollés (2012) come along, and I don’t know what to think.
A large part of the problem is that their methods go way over my head. I get the gist of their message. They figured out the relative ages of the RNA and protein components of the ribosome. The protein-synthesis parts – RNA and protein alike – turned out relatively new. They also found that the oldest protein parts interact with the oldest RNA parts – and seem to have coevolved. That, they say, would suggest that RNA and fairly large pieces of protein had a common history together before the future ribosome became capable of making proteins.
Yes, that means either that RNA didn’t invent proteins, or at the very least, that the “inventor” was not a precursor of the ribosome.
I really really don’t want to believe the former, and the latter possibility is a butchery of Occam’s razor without further evidence. But what else is left, if the study is correct?
One part of their results that I found intriguing is the structural similarity of the most ancient parts of ribosomal RNA to – you’d never guess – lab-evolved RNA-copying ribozymes. That is… oh, I don’t really know what it is, aside from “fascinating”. Did the ribosome start out as replication machinery, and turn into a protein factory only later? Or are the structures similar because reading the primitive genetic code required the same sort of molecular machine as copying RNA? Or is it even just coincidence?
And this is why I need a good science blogger. I need someone who deeply understands the paper and can translate it into something I can digest. Because at the moment, I can’t make heads or tails of this. I’m rather attached to the RNA world; it makes sense to me, and as far as scientific hypotheses go, it’s simply beautiful. Yet I can’t point to any obviously bullshit reasoning in the new study, other than where they seem to imply that because modern ribosomes need proteins to work, proteins must have been present in the ribosome from the start. (Which is a bit like every damn irreducible complexity argument advanced by creationists.) I just don’t have a good enough grasp on the methodology to tell whether it’s all solid or whether any of it is dodgy. Words fail to express how much that bugs me.
 Lincoln and Joyce (2009) and Wochner et al. (2011) came tantalisingly close to making/evolving the right sort of RNA molecule in the lab. The former’s pair of ribozymes can only copy each other by stitching together two half-ribozymes, but they can keep going at it forever and ever. Wochner et al.’s molecule can copy RNA using single letters as ingredients, but it runs out of steam after 90 or so of them. That’s several times better than the previous record, but still not long enough for the ribozyme to replicate its twice-as-long self.
 This excellent video describes one way it could have happened. When it comes to science education, cdk007 never fails to deliver!
 Including attaching amino acids to other RNA molecules (Turk et al., 2010) – look up tRNA if you don’t see why this is exciting 😉
Cech TR (2000) The ribosome is a ribozyme. Science 289:878-879
Harish A & Caetano-Anollés G (2012) Ribosomal history reveals origins of modern protein synthesis. PLoS ONE 7:e32776
Lincoln TA & Joyce GF (2009) Self-sustained replication of an RNA enzyme. Science 323:1229-1232
Turk RM et al. (2010) Multiple translational products from a five-nucleotide ribozyme. PNAS 107:4585-4589
Wochner A et al. (2011) Ribozyme-catalyzed transcription of an active ribozyme. Science 332:209-212