The idea that life’s deepest, oldest roots were laid down by RNA molecules that evolved ever more complexity has dominated the origins-of-life field for the past few decades, reigning over competing theories that started instead with peptides or DNA.
But recently, the field has shifted toward theories that include more than one protagonist. One that’s gained particular momentum is the idea that RNAs and peptides coevolved complexity, and that their intermingling sparked life as we know it.
Now, a new study published in Nature breathes fire into an “RNA-peptide world” by suggesting a plausible pathway for how early RNA molecules may have enabled peptides to grow directly on them, like mushrooms growing on a tree. Those peptides may in turn have stabilized the RNA molecules, allowing them space to complexify. This coevolution of two of life’s key players as a single mixed, “chimeric” molecule may have been the very start of protein production, and a step toward a primitive version of a ribosome.
“It turns out that they could have actually helped one another,” said Claudia Bonfio, a junior group leader at the Institute of Supramolecular Science and Engineering in Strasbourg, France, who wrote a commentary that accompanied the paper. Studies have shown that the raw materials for both peptides and RNA would likely have been present at the start of life, so this paper takes the view, “Why should we just focus on RNA?” Bonfio said.
The work opens new directions to explore the origins of life, said Yitzhak Tor, a professor of chemistry and biochemistry at the University of California San Diego, who was not part of the study but is a longtime collaborator with the authors. “Now you need to consider the interplay between two different biomolecules.”
It’s a “highly intriguing demonstration,” said Andro Rios, a research scientist at the Blue Marble Space Institute of Science and NASA’s Ames Research Center.
The findings also explain a major chicken-and-egg conundrum that has bedeviled researchers studying life’s origin: How did proteins form before the evolution of the ribosome — the cellular machine that churns out proteins in modern cells — when the ribosome is partly made up of proteins itself?
When cells need to make proteins, their genes spin out long threads of messenger RNA (mRNA) that encodes very precise recipes for making them. Ribosomes slide over these recipes to read them and assemble the amino acids that correspond to each step, with the help of their amino acid suppliers: molecules called transfer RNA (tRNA) that continuously dive in as the process unfolds. The ribosome transfers a growing peptide chain onto each new amino acid brought in by tRNAs. These chains get longer and longer and eventually fold into functional proteins.
It’s unlikely, however, that proteins formed in a similar way 3.5 billion years ago. The bonds that hold the peptides on the tRNA molecules are rather weak. Without a ribosome available to provide shelter, water molecules would break these bonds before peptides could form, making the process unfeasible in the harsh watery conditions of the primordial world.
But most people are focusing on re-creating the familiar process of protein translation in a simpler form, said Thomas Carell, senior author of the new paper and the chair for organic chemistry at the Ludwig Maximilian University of Munich. What if ancient translation looked very different from its modern form?
Carell and his team started to dig into this idea, looking for stronger bonds that might have survived in primordial conditions. That’s how they zoned in on the often-overlooked molecules called noncanonical nucleotides. The genetic code of RNA is typically written with just four bases (adenine, guanine, cytosine and uracil), but nucleotides with other bases are also present in many RNA molecules that do other jobs — including helping with protein production in the ribosome. These unusual nucleotides can attach to amino acids with a chemical bond that’s much stronger than the one that attaches amino acids to the tRNA molecules.