Chemists say they have solved a crucial problem in a theory about the beginning of life by showing that RNA molecules can link short chains of amino acids together.
The results, published May 11 in Nature1support a variation of the “RNA world” hypothesis, which proposes that the first organisms, prior to the evolution of DNA and the proteins it encoded, were based on strands of RNA, a molecule that carried both genetic information and sequences of the nucleosides can store A, C, G and U – and act as a catalyst for chemical reactions.
The discovery “opens up far-reaching and fundamentally new avenues for early chemical evolution,” says Bill Martin, who studies molecular evolution at Heinrich Heine University in Düsseldorf, Germany.
In an RNA world, according to standard theory, life could have existed as complex proto-RNA strands that could both copy themselves and compete with other strands. Later, these “RNA enzymes” might have evolved the ability to build proteins and eventually transfer their genetic information into more stable DNA. Exactly how this could happen has been an open question, in part because RNA-based catalysts alone are much less efficient than the protein-based enzymes now found in all living cells. “Although [RNA] When catalysts were discovered, their catalytic power is dreadful,” says Thomas Carell, an organic chemist at the Ludwig Maximilian University of Munich in Germany.
In investigating this puzzle, Carell and his collaborators were inspired by the role that RNA plays in building proteins in all modern organisms: a strand of RNA that encodes a gene (usually copied from a sequence of DNA bases) runs through it a large molecular machine called a ribosome that builds the corresponding protein amino acid by amino acid.
Unlike most enzymes, the ribosome itself consists not only of proteins but also of RNA segments – and these play an important role in the synthesis of proteins. In addition, the ribosome contains modified versions of standard RNA nucleosides A, C, G, and U. These exotic nucleosides have long been thought of as possible remnants of a primordial broth.
Carell’s team built a synthetic RNA molecule containing two such modified nucleosides by joining together 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 sideways to bind with the second exotic nucleoside next to it. The team then separated their original strands of RNA and brought in a fresh one that carried its own amino acid. This was in the right position to form a strong covalent bond with the amino acid previously attached to the second strand. The process went step by step, growing a short chain of amino acids – a mini-protein called a peptide – which got attached to the RNA. Forming bonds between amino acids requires energy, which the researchers provided by prepping the amino acids with different reactants in the solution.
“This is a very exciting finding,” says Martin, “not only because it reveals a new pathway for RNA-based peptide formation, but because it also reveals a new evolutionary significance for the naturally occurring modified RNA bases.” The results point in the right direction suggests an important role that RNA plays in the origin of life, but that RNA alone is not required for self-replication, Martin adds.
Loren Williams, a biophysical chemist at the Georgia Institute of Technology in Atlanta, agrees. “If the origins of RNA and proteins are linked and their formation is not independent of each other, then the math shifts radically in favor of an RNA-protein world and away from an RNA world,” he says.
To show that this is a plausible origin of life, scientists need to take several more steps. The peptides that form on the team’s RNA consist of a random sequence of amino acids rather than one determined by information stored in the RNA. Carell says that larger RNA structures may have stretches that fold into shapes that “recognize” specific amino acids at specific locations, creating a well-defined structure. And some of these complex RNA-peptide hybrids could have catalytic properties and face evolutionary pressures to become more efficient. “If the molecule can replicate, you have something like a mini-organism,” says Carell.