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The mystery of why life uses molecules with specific orientations has deepened with a NASA-funded discovery that RNA — a key molecule thought to have potentially held the instructions for life before DNA emerged — can favor making the building blocks of proteins in either the left-hand or the right-hand orientation. Resolving this mystery could provide clues to the origin of life. The findings appear in research recently published in Nature Communications.
Proteins are the workhorse molecules of life, used in everything from structures like hair to enzymes (catalysts that speed up or regulate chemical reactions). Just as the 26 letters of the alphabet are arranged in limitless combinations to make words, life uses 20 different amino acid building blocks in a huge variety of arrangements to make millions of different proteins. Some amino acid molecules can be built in two ways, such that mirror-image versions exist, like your hands, and life uses the left-handed variety of these amino acids. Although life based on right-handed amino acids would presumably work fine, the two mirror images are rarely mixed in biology, a characteristic of life called homochirality. It is a mystery to scientists why life chose the left-handed variety over the right-handed one.
DNA (deoxyribonucleic acid) is the molecule that holds the instructions for building and running a living organism. However, DNA is complex and specialized; it “subcontracts” the work of reading the instructions to RNA (ribonucleic acid) molecules and building proteins to ribosome molecules. DNA’s specialization and complexity lead scientists to think that something simpler should have preceded it billions of years ago during the early evolution of life. A leading candidate for this is RNA, which can both store genetic information and build proteins. The hypothesis that RNA may have preceded DNA is called the “RNA world” hypothesis.
If the RNA world proposition is correct, then perhaps something about RNA caused it to favor building left-handed proteins over right-handed ones. However, the new work did not support this idea, deepening the mystery of why life went with left-handed proteins.
The experiment tested RNA molecules that act like enzymes to build proteins, called ribozymes. “The experiment demonstrated that ribozymes can favor either left- or right-handed amino acids, indicating that RNA worlds, in general, would not necessarily have a strong bias for the form of amino acids we observe in biology now,” said Irene Chen, of the University of California, Los Angeles (UCLA) Samueli School of Engineering, corresponding author of the Nature Communications paper.
In the experiment, the researchers simulated what could have been early-Earth conditions of the RNA world. They incubated a solution containing ribozymes and amino acid precursors to see the relative percentages of the right-handed and left-handed amino acid, phenylalanine, that it would help produce. They tested 15 different ribozyme combinations and found that ribozymes can favor either left-handed or right-handed amino acids. This suggested that RNA did not initially have a predisposed chemical bias for one form of amino acids. This lack of preference challenges the notion that early life was predisposed to select left-handed-amino acids, which dominate in modern proteins.
“The findings suggest that life’s eventual homochirality might not be a result of chemical determinism but could have emerged through later evolutionary pressures,” said co-author Alberto Vázquez-Salazar, a UCLA postdoctoral scholar and member of Chen’s research group.
Earth’s prebiotic history lies beyond the oldest part of the fossil record, which has been erased by plate tectonics, the slow churning of Earth’s crust. During that time, the planet was likely bombarded by asteroids, which may have delivered some of life’s building blocks, such as amino acids. In parallel to chemical experiments, other origin-of-life researchers have been looking at molecular evidence from meteorites and asteroids.
“Understanding the chemical properties of life helps us know what to look for in our search for life across the solar system,” said co-author Jason Dworkin, senior scientist for astrobiology at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, and director of Goddard’s Astrobiology Analytical Laboratory.
Dworkin is the project scientist on NASA’s OSIRIS-REx mission, which extracted samples from the asteroid Bennu and delivered them to Earth last year for further study.
“We are analyzing OSIRIS-REx samples for the chirality (handedness) of individual amino acids, and in the future, samples from Mars will also be tested in laboratories for evidence of life including ribozymes and proteins,” said Dworkin.
The research was supported by grants from NASA, the Simons Foundation Collaboration on the Origin of Life, and the National Science Foundation. Vázquez-Salazar acknowledges support through the NASA Postdoctoral Program, which is administered by Oak Ridge Associated Universities under contract with NASA.
