Before DNA, before RNA: Life in the hodge-podge world

Take note, DNA and RNA: it's not all about you. Life on Earth may have begun with a splash of TNA – a different kind of genetic material altogether.

Because RNA can do many things at once, those studying the origins of life have long thought that it was the first genetic material. But the discovery that a chemical relative called TNA can perform one of RNA's defining functions calls this into question. Instead, the very first forms of life may have used a mix of genetic materials.

RNA, DNA… TNA

Today, most life bar some viruses uses DNA to store information, and RNA to execute the instructions encoded by that DNA. However, many biologists think that the earliest forms of life used RNA for everything, with little or no help from DNA.

A key piece of evidence for this "RNA world" hypothesis is that RNA is a jack of all trades. It can both store genetic information and act as an enzyme, seemingly making it the ideal molecule to start life from scratch.

Now it seems TNA might have been just as capable, although it is not found in nature today.

It differs from RNA and DNA in its sugar backbone: TNA uses threose where RNA uses ribose and DNA deoxyribose. That gives TNA a key advantage, says John Chaput of Arizona State University in Tempe: it is a smaller molecule than ribose or deoxyribose, possibly making TNA easier to form.

Chaput and his colleagues have now created a TNA molecule that folds into a three-dimensional shape and clamps onto a specific protein. These are key steps towards creating a TNA enzyme that can control a chemical reaction, just like RNA.

The team took a library of TNAs and evolved them in the presence of a protein. After three generations, a TNA turned up that had a complex folded shape like an enzyme and could bind to the protein.

No TNA world

That doesn't mean TNA was the original genetic material, though. Chaput thinks it probably wasn't, if only because the chemistry of early Earth was so messy that TNA would not have arisen on its own. Rather, many different kinds of genetic material probably formed in a genetic hodge-podge. "The most likely scenario is that nature sampled lots of different things," says Chaput.

That's in line with a recent study by Nobel prizewinner Jack Szostak of Harvard University and colleagues. He created mosaic nucleic acids that were half DNA, half RNA. Like Chaput's TNA, some of these could bind to target molecules (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.1107113108).

However, there are problems with the hodge-podge world hypothesis. For one thing, there is no trace of TNA or its cousins in modern organisms. For another, although TNA looks simpler than RNA, we can't be sure it was easier to make some 4 billion years ago because no one has actually made it in the conditions that existed on Earth before life began, says John Sutherland of the MRC Laboratory of Molecular Biology in Cambridge, UK.

Chaput points out that we still know very little about what TNA can do, because the technology to evolve the molecules in the lab is so new. The research, he says, is just getting going.

Journal reference: Nature Chemistry, DOI: 10.1038/nchem.1241

Cousins of DNA

TNA is just one of many nucleic acids that may have been important in the first life on Earth. Here are three others.

PNA (peptide nucleic acid) ditches the sugar in its backbone and inserts a peptide instead, so it is more closely related to proteins. Like DNA, it can form double strands with itself, as well as with DNA or RNA, making it a promising genetic system (Science, DOI: 10.1126/science.1174577). It is also easy to make long PNA molecules in the conditions of prebiotic Earth, even at temperatures of 100 °C (Proceedings of the National Academy of Sciences, DOI: 10.1073/pnas.97.8.3868).

GNA (glycol nucleic acid) is even simpler than TNA, with just three carbon atoms in its backbone, yet can still form helical molecules, much like DNA (The Journal of Organic Chemistry, DOI: 10.1021/jo201469b).

ANA (amyloid nucleic acid) consists of nucleic acids attached to amyloid proteins, infamous for their role in Alzheimer's disease. ANA fibres have been suggested as the first organisms (PLoS One, DOI: 10.1371/journal.pone.0019125), because the amyloid could protect genetic material contained within.