In all present-day organisms, information encoded in DNA, the genetic material of the cell, is converted via an RNA intermediate into proteins, the molecular machines of the cell. However, evidence suggests that in a distant evolutionary past our single-celled ancestors used only RNA for both genetic information storage and metabolism. A cornerstone of this “RNA world” would have been an RNA able to replicate itself. The emergence of such a RNA replicase is widely considered to mark the key point in the origin of life. Research from Philipp Holliger’s group in the LMB’s PNAC Division has shed new light on how the RNA world, and its RNA replicase, might have first become dependent on short proteins (peptides), beginning the transition to our modern biology.
Some of the most ancient proteins are found in the core of the ribosome, and may derive from the RNA world. Shunsuke Tagami and James Attwater from Philipp’s group examined the ability of short peptide segments of these ancient proteins to enhance the function of an RNA polymerase ribozyme (RPR), a modern-day counterpart of the primordial RNA replicase. Some of these ancient ribosomal peptides strongly increased RPR function and and were found to contain positively charged amino acids, which seem to allow the peptide to act as a bridge between RNA molecules awaiting replication and RPR replicase. Using these peptides the RPR replicase needed much lower levels of magnesium ions, a previously necessary cofactor which is also destructive to RNA. In addition, the peptides accelerated RPR evolution and allowed the RPR to function within a simple membranous ‘protocell’, an essential step for the emergence of cellular life billions of years ago. This illustrates the functional and evolutionary advantages that peptides could have conveyed. Since these peptides are so simple – often short strings of a single type of amino acid – this work also suggests ways in which peptides might have become incorporated into the molecular fabric of early life, even before the emergence of the genetic code and translation.
Life depends on the intricate interplay of myriads of different biomolecules, but how such interdependent molecular networks arose at the origin of life remains a mystery. This work illustrates how a simple example of molecular “symbiosis”, a mutually beneficial interaction between different classes of molecules such as nucleic acids like RNA, peptides and lipids could have emerged, giving rise to the first primitive cells. Such work could also provide the foundation for the design and construction of molecular systems with life-like properties such as growth, division and evolution.
This work was funded by the MRC, the Japanese Society for the Promotion of Science and the Human Frontiers Science Program.