The new research, focused on structures that could have been around during the RNA world, suggests RNA did not initially have a predisposed chemical bias for one chiral form of amino acids.
Could life on Earth have looked fundamentally different -- all the way down to the building blocks of our genetic code and the proteins that form our bodies? And could it be possible that life as we know it depends on whether these molecules are left- or right-handed?
A recent paper in Nature Communications from researchers at UCLA and NASA's Goddard Space Flight Center in Greenbelt, Maryland, offers new insight into the mystery of life. The study found that when it comes to the likelihood of the earliest life on Earth taking a different shape, it was effectively a chemical toss-up.
In chemistry, molecules can exist in two distinct 3D mirror-image forms. But these identical twin molecules are not fully symmetrical. Like a right hand and left hand, they cannot be superimposed on top of each other. This property is called chirality.
Chirality exists in sugars -- specifically the "ribose" in DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) -- as well as the 20 or so common amino acids, which act as the building blocks of all proteins that carry out genetic instructions.
All life on Earth is made up of "right-handed" sugars and "left-handed" amino acids.
Their mirror-image counterparts exist as well. Theoretically, those geometric twin molecules, known as enantiomers, could also act as the building blocks of life. But here on Earth, all molecules involved in life have exclusively the same chirality.
The right-handed sugars in DNA and RNA and left-handed amino acids are thought to have evolved to work with each other during the early Earth, where single-stranded RNA could have been the first molecules that gave rise to DNA and amino acids. This hypothetical time period around 4 billion years ago is often referred to as the "RNA world."
Previous experiments suggest life is predisposed to the molecular homochirality -- the preference for "one-handedness" as we see today -- but those studies focused on existing molecular biology structures.
The new research focused on structures that could have been around during the RNA world. Their experiments centered around ribozymes -- small bits of RNA known to catalyze chemical reactions. The researchers wanted to see whether right-handed ribozymes always build left-handed amino acids, or if there was some variation.
To test their hypothesis, the researchers simulated what could have been RNA world's early Earth conditions. They incubated a solution containing ribozymes and amino acid precursors to see the relative percentages of the right-handed versus left-handed versions of phenylalanine, an amino acid the solution would help produce. After testing 15 different ribozymes, they found that right-handed ribozymes can favor either left-handed or right-handed amino acids. This suggests that RNA did not initially have a predisposed chemical bias for one chiral form of amino acids.
"Earlier work in this area was inspired more by chemical structures in our existing biology, whereas our study looked at any RNAs that would react with the activated amino acid at any position along the strand," said study leader Irene Chen, professor of chemical and biomolecular engineering at the UCLA Samueli School of Engineering. "What we found is that these ribozymes, while having little to do with our current biology, may indeed represent a potential 'road not taken' by life on Earth."
This lack of preference challenges the notion that early life was predisposed to select left-handed-amino acids, which dominate in modern proteins. The research also offers insights on how to look for chemical signals of extraterrestrial life.
"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 study author Alberto Vázquez-Salazar, a UCLA Samueli postdoctoral scholar and member of Chen's research group. "This work emphasizes the flexibility and adaptability of RNA as a model for studying early evolution and the emergence of life, particularly regarding the origins of biological homochirality."
Earth's pre-life history lies beyond the oldest part of the fossil record, which has been steadily destroyed by plate tectonics. During that time, the planet was likely bombarded by asteroids. Alongside chemical experiments, other origin-of-life researchers have been looking at molecular evidence from meteorites.
"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 Goddard and director of the 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," Dworkin said.
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.
Other authors on the paper include Josh Kenchel, Evan Janzen, Reno Wells and Krishna Brunton, who were former members of Chen's research group at UC Santa Barbara; Kyle Schultz, part of her group at UCLA; Ziwei Liu, a researcher at the University of Cambridge; Weiwei Li, a graduate student at UC Santa Barbara's Bren School of Environmental Science & Management; and Eric Parker, an astrochemist with Goddard's Astrobiology Analytical Laboratory.
Chen also holds a faculty appointment in the UCLA Chemistry & Biochemistry Department.