RNA, the True Secret of Life?

In THE DOUBLE HELIX A Personal Account of the Discovery of the Structure of DNA, James Watson narrates the famous story of Francis Crick bursting into the Eagle Pub to tell everyone within earshot that he had found the secret of life.

Certainly, DNA is one secret of life and (leaving aside a few viruses – which aren’t really alive) is a common (and rather vital) denominator of all terrestrial life. But life has many secrets. Since Crick and Watson (building on the often neglected contributions of Rosalind Franklin) elucidated the structure of DNA, life has revealed more and more of those secrets. But one important secret remains almost as well kept as ever: the secret of just how life emerged in the first place.

There are several rival theories as to how life may have originated on earth (or some other space-rock) but the question of just how we got from a non-living “Primordial Soup” to DNA-based life presents a particular puzzle.

What struck Crick and Watson immediately as they surveyed the model double helix they had constructed were the implications of that structure for DNA replication. Each strand of the DNA double helix comprises a series of nucleotides and (as was later found) these nucleotides constitute the individual “letters” of the DNA code. The two strands of the DNA helix are complementary and the sequence of one strand can be inferred from the sequence of the other. If two strands are separated and furnished with a supply of fresh nucleotides, each strand can serve as the template for the assembly of a new copy of the original double helix.

But if all DNA could do were to serve as a template for making more copies of itself, it would be pretty boring stuff. What makes DNA interesting is that it also serves as a template for making proteins.

It is important to realize here that while proteins are often structural molecules – like muscle proteins – they may also be enzymes – like the enzymes often included in modern detergents. Enzymes are tightly folded proteins that “catalyse” (ie speed-up without getting directly involved themselves) other reactions. Enzymes have specific shapes which allow them to bind to other molecules and thereby encourage those other molecules to react with one another. Enzymes are crucially important for regulating what goes on inside living things.

The way in which proteins (including enzymes) are produced from DNA is quite complex. The first stage involves the creation of multiple RNA copies of the “master” DNA template. RNA is a very similar molecule to DNA – consisting of long chains of nucleotides – but it is normally single-stranded. The second stage involves the creation (from the RNA templates) of long chains of amino acids (which is what proteins are).

But here’s the thing ....

In order to make proteins from DNA, and even to replicate DNA, you need to have proteins (enzymes) that make everything work properly. And where do these enzymes come from? They are coded for by the DNA.

While this system works perfectly well once it is all in place, it is difficult to imagine how the system ever got going in the first place. The solution to this conundrum is that the DNA/protein system is probably not what originally got going. It is almost certainly a refinement of a far simpler system.

It is a feature of the aforementioned single stranded RNA molecule that (as well as serving as a DNA analogue – at least for one strand of DNA) it can also adopt tightly folded configurations which double-stranded DNA could never imitate. This means that, in certain respects, RNA molecules are rather like protein molecules and, it was discovered, can act like primitive enzymes that catalyse other reactions.

Once you have RNA molecules (formed entirely randomly as the primordial soup dribbled down hot rocks) that just happen to be able to catalyse (however poorly) reactions that result in RNA copying, you’re away! The “chicken and egg” problem presented by the DNA/protein system is circumvented. A self-catalysing RNA system will, given a supply of nucleotides, keep on replicating until the cows come home – which, given that replicating systems constantly mutate and the best mutations are chosen by natural selection (and later on in the process by human breeders) is exactly what happened in the end.

Nobody knows for certain how terrestrial life began, but the RNA hypothesis is a strong contender. We may never know exactly what did happen but there is a plethora of exciting research going on with RNA (and similar nucleotide polymers) that is confirming the plausibility of some theories as to what might have happened.

So next time you are enjoying a pint in a university-town, watch out for someone bursting in and announcing that the real secret of life has just been found.