One-Handed Life

Scientists at The Skaggs Institute for Chemical Biology, a part of The Scripps Research Institute (TSRI) in Southern California, published a paper in the February 15, 2001, issue of Nature that suggests a possible answer to how one of the early steps necessary for the origins of life arose.

Peptide replicating

The peptide molecule used by the Ghadiri group (bottom) is able to self-replicate: using other molecules in its environment (top), it builds a copy of itself. Credit: Ghadiri group

Principal Investigator M. Reza Ghadiri, Ph.D., Professor of Chemistry at TSRI and a member of the NASA Astrobiology Institute, 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 Dr. 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 in part by these replication processes.

Self-replication cycle

The self-replication cycle of the peptide tubes is chiralselective that is, a left-handed tube produces left-handed tubes, and a right-handed tube produces right-handed tubes. Credit: Ghadiri group

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?

cyclic peptide sequence

Example of a cyclic (ring-shaped) sequence of peptides.Credit: Ghadiri group

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.

cyclic peptides assembled into tubes

The cyclic peptides naturally assemble themselves into long tubes. The tubes then self-replicate. Credit: Ghadiri group

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.



Related Web Sites

Ghadiri Group Home Page

Lifelines: How Life Got the Upper Hand (Nature Science Updates)

Biochemistry: Single-Handed Cooperation (Nature, registration required)

A Chiroselective Peptide Replicator (Nature, registration required)

Can Protein Spring into Life? – Ghadhiri’s earlier experiments with self-replicating molecules. (New Scientist)