New Study By Scripps Scientists Sheds Light On Key Step For Origin Of Life

Principal Investigator M. Reza Ghadiri, Ph.D., Professor of Chemistry at TSRI, has created a biological polymer that can discriminate between two types of building blocks, taking those that are similar and building a copy of itself with them.

The research article, "A Chiroselective Peptide Replicator," is authored by Alan Saghatelian, Yohei Yokobayashi, Kathy Soltani, and M. Reza Ghadiri.

Information transfer is one of the most fundamental requirements for life. Human DNA, for instance, lives in cell nuclei, where it makes RNA and protein products that carry out the work of the cell, (and in the big picture) our bodies. Part of this work is replicating and dividing the DNA so that the cell can split into two new daughter cells. Life is defined by these replication processes.

What is also known is that all the DNA, RNA, and protein molecules in our bodies are all homochiral. That is, the L-amino acids from which proteins are made and the D-riboses from which DNA and RNA are made are all chiral molecules. They come in two non-superimposable mirror image forms, like your right and left hand. Our bodies can only use the L-form of amino acids (left-handed) and the D-form of ribose molecules (right-handed).

Since only the correct forms of these building blocks of life can be used, a natural question arises. How did the very first biological molecules assemble out of a presumed mixture of right and left- handed building blocks?

To answer this, Ghadiri and his colleagues asked if a molecule that was correctly composed of all right or all left-handed components could replicate itself. They used peptides--short proteins of 32 amino acids--that naturally fold into a long helix and stick to another similar peptide, somewhat like the double barrels of a shotgun. They mixed right and left-handed versions of these peptides together with a mixture of their right and left-hand components.

For the "template" peptides to replicate, the correctly-handed components in the mixture would have to stick to the correct location on the peptides and then link up, forming exact copies of the template molecules, and this is exactly what they observed. The left-handed templates made more left-handed copies and the right-handed templates made right-handed copies from the mixed components.

Not only did the results show that the peptides favored the synthesis of correct duplicates, but the duplicates auto-catalyzed the reaction, speeding it up. They further discovered that if they added "mutant" peptide templates with a single incorrectly handed molecule, these would not make more mutant templates. They would instead correct the mistake and catalyze the formation of new molecules with the correct composition.

"That is astonishing," says Ghadiri. "Based on [our] understanding, polypeptides can self- replicate, form complex networks, error correct, form mutual systems, they have all sorts of emergent properties, and they can now do homochiral amplification."

The proof that a peptide system can self-replicate chiralselectively is strong evidence that such peptide chemistry could play an important role in the gestation of life on earth and elsewhere in the universe.

The research was funded (in part) by the NASA Astrobiology Institute, a national research consortium whose Central Office is located at NASA's Ames Research Center in Mt. View, CA The NAI, led by Director Baruch Blumberg, M.D, Ph.D. (Nobel laureate, '76), comprises 11 lead TEAMS and has international Affiliate and Associate Members.