NOTE TO JOURNALISTS: Copies of the journal article in Nature are available from Purdue's News Service, 765-494-2096.
WEST LAFAYETTE, Ind. -- A Purdue University study shows that proteins may have played a leading role in the origin of life.
Scientists, looking for clues as to how life began at a molecular level, have long considered nucleic acids, such as DNA and RNA, as the star players due to their rare ability to replicate themselves and adapt to changes.
But Purdue University scientist Jean Chmielewski has developed a system made up of four peptides -- the building blocks for proteins -- that can replicate itself and is capable of adapting to changes in the environment. The findings, published in the Dec. 3 issue of the scientific journal Nature, expand the scientific view of how life began.
"This system is the first to show that a peptide-based system has the ability to replicate in novel and adaptive ways," Chmielewski says.
Scientists have long searched for the simplest self-replicating systems as clues to how life may have begun, Chmielewski says.
"The molecules of choice for a long time were molecules like DNA and RNA, because they are known to replicate in living organisms," she says. "The possibility of other self-replicating molecules had also been considered, though until recent years there were no other molecules that were known to be able to reproduce themselves."
In the past 20 years, scientists have found that some other nucleotide-based molecules can replicate themselves. Two years ago, a study published by researchers at Scripps Research Institute showed that some peptides, or pieces of small proteins, also can self replicate.
However, these molecules fell short of DNA and RNA's ability to cross replicate, a feat that allows the nucleic acids to replicate through the use of complimentary molecules.
"Self replication would occur if proteins interact with peptide fragments to create an identical copy of themselves," Chmielewski says. "For example, protein AB might interact with peptide A and peptide B and then catalyze to form a new AB protein.
In cross replication, the proteins would interact with peptide fragments that are complimentary to it, forming a new type of molecule, she says. For example, protein CD might also interact with peptide A and peptide B to form a AB proteins.
"These cross-replicating molecules are the types of molecules that actually have the potential for building life," Chmielewski says. "It is believed that within a living cell, virtually no substance catalyzes its own formation, so you when you talk about a theoretical system that can create life, you want a chemical system in which both self replication and cross replication occurs."
In the most recent round of experiments, the Scripps group recently developed a system using three peptides that could self replicate and cross replicate through four different chemical reactions. Chmielewski and her group set out to see if they could produce a more complex peptide-based replicating system.
Her group designed a system using four peptides that was capable of carrying out 11 different chemical reactions -- a system almost three times more complex than the Scripps system. Four peptide fragments, called E1, E2, K1 and K2, were used as the feedstock to produce four proteins, namely E1E2, K1K2, E1K2 and K1E2.
The study showed that the four proteins replicated themselves through self replication -- acting as templates for their own formation -- and also used a total of seven cross replication pathways to produce additional new copies.
"This is the most complex replicating system of its kind to date" Chmielewski says. "This work clearly demonstrates that peptides should be considered in discussions over the nature of the molecular origins of life".
In addition, Chmielewski's group showed that changes to the environment of the reaction had a profound effect on the types of peptides that could be formed.
"If you put the four peptides together, you have the potential to form all of the products, but we can modify the environment of the reaction, such as pH or salt concentration, and only a single molecule can replicate itself and the rest are lost," Chmielewski says.
This ability to survive and reproduce in the face of environmental changes is the basis of Darwinian selection, and it might have allowed for the evolution of early life forms over time, she adds.
"It is interesting when we imagine that perhaps, in a very early system, only certain molecules were used in the formation of life and others were left behind," Chmielewski says.
Though her study may help expand the current view of how life formed on Earth, Chmielewski notes that the answers may never be known.
"There is no real way to prove any of this or travel back in time to see how life started," she says. "All we can do is show that various other kinds of molecules are capable of replicating in various ways, and these molecules may have played a role in creating life."
ABSTRACT: Selective Amplification via Auto- and Cross-Catalysis in a
Replicating Peptide System
Jean Chmielewski, Shao Yao, Indraneel Ghosh, Reena Zutshi
The successful replication of chemical entities such as DNA and RNA is essential for the transfer of information to succeeding generations. Self replicating chemical systems of nucleotide-based molecules, adenineKemp's triacid conjugates and peptides, have been successfully designed. A living cell, however, is a collective autocatalytic system in which virtually no molecule catalyzes its own production. Therefore, the development of a system in which not only autocatalysis, but also crosscatalysis, can occur is currently a subject of intensive studies. We describe here the first four-component peptide-based system that is capable of both auto- and cross- catalysis. Furthermore, we have selectively amplified one or more of the products by changing the environmental conditions, such as pH or salt concentration, within the reaction.
Journal
Nature