DNA Just One of More Than 1 Million Possible 'Genetic Molecules,' Scientists Find | Live Science - "Scientists used a computer program to uncover more than 1 million molecules that could potentially store genetic information, just like DNA."
noting journal article
One Among Millions: The Chemical Space of Nucleic Acid-Like Molecules | Journal of Chemical Information and Modeling

Every cellular organism with known or reasonably inferred biochemistry uses DNA as its carrier of heredity. Some viruses do also, with the others instead using a close chemical relative, RNA. DNA and RNA are collectively nucleic acids, and they have a shared structure.

R - N
R - N
R - N

P = phosphate, R = (deoxy)ribose, N = nucleobase. Two strands fit against each other in the famous double-helix structure, with nucleobases from each strand fitting against each other.

But are there alternatives? This research explored numerous possible alternative strand backbones to the nucleic-acid (deoxy)ribose-phosphate backbone. "These sets contain 86,007 (CHO) and 75,309 (CHNO) compositionally isomeric structures, representing 706,568 CHO and 454,422 CHNO stereoisomers, that diversely and densely occupy this space." from the journal-paper abstract.

Steroisomers = mirror-image variants. Counting them separately gives 1,161,010 possibilities, while lumping together such variants gives 161,316 possibilities.
"We were surprised by the outcome of this computation," co-author Markus Meringer, a chemist at the German Aerospace Center in Cologne, said in the statement. "It would be very difficult to estimate a priori that there are more than a million nucleic-acid like scaffolds. Now we know, and we can start looking into testing some of these in the lab."

The multitude of look-alikes may clarify the story of how life on Earth came to be, before DNA and RNA dominated the world of biology. Theoretically, evolution may have performed "test runs" with some of these other molecules before settling on nucleic acids as the best conveyors of genetic data, the authors suggested.
That gets around a big problem in origin-of-life research. It involves two main lines of research, lines that can be called forward and backward. The forward research works from prebiotic chemistry, and the backward research works from evolution of known organisms.

The forward research has produced numerous building blocks of known organisms, like the smaller amino acids and some nucleobases. But some building blocks remain difficult, like ribose. One can make ribose nonbiologically, with the Butlerov formose reaction, but it swamps its ribose with a lot of other stuff. For starters, ribose has four asymmetric carbon atoms, giving 2^4 = 16 stereoisomer variants.

The backward research has produced disappointing amounts of complexity. The Last Universal Common Ancestor of all organisms with known biochemistry is an organism with complexity comparable to what many present-day prokaryotes have. Present-day methanogens are much like the reconstructed LUCA. That organism had a DNA genome, the familiar transcription and translation apparatus, complete biosynthesis, and getting its energy from combining carbon dioxide and hydrogen from its environment.

Pre-LUCA evolution has been harder to reconstruct, and the most success that has emerged is the "RNA world". It states that some early organisms had RNA as both information storage and enzyme, with proteins a later elaboration. In fact, the translation-to-protein apparatus is built around its RNA parts. DNA is modified RNA that contains master copies of genetic information, its only function.

The main criticism of the RNA world that I've seen is the origin of its RNA - it's hard to make ribose prebiotically.


This new research provides a valuable hint in origin-of-life research. Among the numerous possible nucleic-acid analogs are likely some that have much easier prebiotic origin. The first organism may have had one of these replicators, with RNA emerging in some descendant as an alternative which eventually took over. It's not very clear what ribose might have that its alternatives don't. Greater chemical stability? Easier biosynthesis?

So the forward and backward research efforts may be able to meet.

This research also has implications for extraterrestrial life. This research suggests that many extraterrestrial organisms may have replicator molecules other than nucleic acids, and that suggests a way of identifying such organisms. However, a cellular organism without nucleic acids may have a separate origin on our planet from our known biota. But wherever the origin locale of such an organism, it would be a very important discovery.