Origin of life theory involving RNA-protein hybrid gains new support


Carell and his colleagues were inspired by ribosomes – shown here translating a strand of RNA.Credit: Omikron/Science Photo Library

Chemists say they have solved a crucial problem in a theory of early life, by demonstrating that RNA molecules can link short chains of amino acids together.

The conclusions, published on May 11 in Nature1support a variant of the “world of RNA” hypothesis, which proposes that before the evolution of DNA and the proteins it encodes, early organisms were based on strands of RNA, a molecule which can both store genetic information — such as A, C, G, and U nucleoside sequences — and act as catalysts for chemical reactions.

The discovery “opens up vast and fundamentally new avenues of pursuit for early chemical evolution,” says Bill Martin, who studies molecular evolution at the Heinrich Heine University of Düsseldorf in Germany.

In a world of RNA, according to standard theory, life could have existed as complex proto-RNA strands capable of both copying themselves and competing with other strands. Later, these “RNA enzymes” could have developed the ability to make proteins and ultimately transfer their genetic information into more stable DNA. How exactly this could happen was an open question, in part because catalysts made from RNA alone are much less efficient than the protein-based enzymes found in all living cells today. “Although [RNA] catalysts have been discovered, their catalytic power is nil,” says Thomas Carell, an organic chemist at the Ludwig Maximilian University of Munich in Germany.

RNA ribosome

Investigating this conundrum, Carell and his collaborators were inspired by the role that RNA plays in how all modern organisms make proteins: a strand of RNA coding for a gene (usually copied from a sequence of DNA bases) passes through a large molecular machine called the ribosome, which builds the corresponding protein one amino acid at a time.

Unlike most enzymes, the ribosome itself is made up not only of proteins, but also of RNA segments – and these play an important role in protein synthesis. Additionally, the ribosome contains modified versions of the standard RNA nucleosides A, C, G, and U. These exotic nucleosides have long been considered possible remnants of a primordial broth.

Carell’s team constructed a synthetic RNA molecule that included two of these modified nucleosides by joining two pieces of RNA commonly found in living cells. At the first of the exotic sites, the synthetic molecule could bind to an amino acid, which then moved laterally to bind to the second exotic nucleoside adjacent to it. The team then separated their original RNA strands and brought in a new one, carrying its own amino acid. It was in the right position to form a strong covalent bond with the amino acid previously attached to the second strand. The process continued step by step, developing a short chain of amino acids – a mini-protein called a peptide – which attached itself to RNA. Forming bonds between amino acids requires energy, which the researchers provided by priming the amino acids with various reagents in solution.

“This is a very exciting finding,” says Martin, “not only because it charts a new pathway for the formation of RNA-based peptides, but because it also reveals new evolutionary significance of natural modified bases. of RNA”. The results point to an important role played by RNA in the origins of life, but without requiring that RNA alone is self-replicating, adds Martin.

Loren Williams, a biophysical chemist at the Georgia Institute of Technology in Atlanta, agrees. “If the origins of RNA and the origins of proteins are linked and their emergence is not independent, then the mathematics changes radically in favor of an RNA-protein world and away from an RNA world”, says- he.

To show that this is a plausible origin of life, scientists must take several additional steps. The peptides that form on the team’s RNA are composed of a random sequence of amino acids, rather than a sequence determined by the information stored in the RNA. Carell says larger RNA structures could have sections that fold into shapes that “recognize” specific amino acids at specific sites, yielding a well-defined structure. And some of these complex RNA-peptide hybrids might have catalytic properties and be under evolutionary pressure to become more efficient. “If the molecule can replicate, you have something like a mini-organism,” says Carell.

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