Organism Sets Mutation Speed Record, May Explain Life's Origins

An uber-primitive plant pathogen made from naked strands of genetic material mutates faster than any other known organism — and it might just illuminate the origins of life.

Called hammerhead viroids, their mutation rates are orders of magnitude more rapid than those of viruses, the next-most-primitive organisms, which are orders of magnitude more rapid than lowly bacteria.

In less academic terms, the hammerhead viroid blueprint of life is being constantly redrawn.

Such accelerated mutation could have been useful four billion years ago, after a few quirky chemicals assembled into ribonucleic acid, or RNA — DNA's single-stranded forerunner.

Mutationrates_2At the time, hypothesize scientists, the pinnacle of life was the RNA replicon: a chunk of ribonucleic acid that didn't copy itself by making proteins, as DNA does, but instead pulled them from the primordial ooze.

Whether hammerhead viroids are descended from replicons isn't known. But in a study published Thursday in Science, University of Valencia plant biologists led by Rafael Sanjuan say the viroids at least resemble that long-lost link in the evolutionary chian.

Their traits could explain how RNA learned to make proteins — the next critical step towards self-assembling DNA and the complex life that flowed from it. And no other hammerhead viroid trait is more remarkable than its mutation rate.

"It's extremely high," said Irene Chen, a Harvard University systems biologist who studies the evolution of molecules. Chen was not involved in the study . "It's right at the Eigen error threshold" — the mutation rate at which replication becomes intrinsically self-destructive because every copy is so error-ridden.

Sanjuan's team used an ingenious trick to quantify the viroids' mutation rate: they measured their death rate.

Hammerhead viroids rely on a 15-molecule structure called the ribozyme to finalize copies of themselves. If a transcription error affects certain parts of the ribozyme, further replication is impossible.

By counting non-replicating viroids in each generation, the researchers calculated that replication produces roughly one mutation for every 400 pieces of RNA.

Such rates produce plenty of haywire copies, a dilemma solved by evolution in two ways: viroids are small, and endowed with prodigious powers of replication.

Their tiny genome means viroids inherit one mistake at a time. And they make so many copies of themselves that it doesn't matter when some are nonviable. Others will succeed — and perhaps improve on the original.

"Error correction mechanisms that reduced mutation rates and allowed replicons to increase their size" probably came next, said Sanjuan.

Chen called an improved ribozyme the "smoking gun" of RNA world evolution. Tantalizingly, she said, it appears that ribosomes — cellular components that assemble simple amino acids into complicated chains — "are just ribozymes, fancily decorated by proteins."

The replicons' updated ribozymes, then, may have led to protein-making RNA, which in turn gave rise to DNA, the ultra-efficient biological information carrier that made it possible for complex life to evolve.



But where did replicons come from? Hammerhead viroids can't tell us — but replicons may well be the product of non-biological evolution.

"Evolutionary dynamics are a universal principle. They can operate with whatever is at hand," said Harvard University evolutionary biologist Martin Nowak after an earlier study on the original formation of RNA.

All that's needed, he said, "is some chemical system that produces all sorts of chemicals, and some have the property of forming strings."