The question of why life uses molecules with specific orientations—favoring left-handed over right-handed structures—has puzzled scientists for years. Recent research published in Nature Communications has added complexity to this mystery by showing that RNA, a molecule believed to predate DNA in the evolution of life, does not inherently favor the left-handed orientation of amino acids that is common in life today. This finding deepens the debate about how life’s molecular asymmetry, known as homochirality, originated.
Proteins are fundamental components of life, acting as building blocks for cells and tissues and functioning as enzymes to regulate biochemical reactions. These proteins are made up of chains of amino acids, the essential building blocks that come in 20 different types. Like the 26 letters of the alphabet forming countless words, amino acids combine in various sequences to produce the diverse proteins that sustain life. A curious property of many amino acids is their “chirality”—they can exist in two mirror-image forms, like a pair of hands. In nature, life almost exclusively relies on the left-handed versions of amino acids, a puzzling phenomenon given that right-handed amino acids could theoretically work just as well.
This unique preference in biology, called homochirality, is evident in all known forms of life, from bacteria to humans. Despite its universality, scientists remain uncertain why life’s chemistry settled on left-handed amino acids. DNA, the carrier of genetic instructions for all known organisms, plays a role in this selection. However, DNA’s complexity and specialization imply that it was not the earliest molecule to drive life’s evolution. This has led researchers to explore the possibility of an “RNA world,” a theoretical period in Earth’s history when RNA might have served as the primary molecule for both genetic storage and catalysis, performing functions now attributed to both DNA and proteins.
RNA’s ability to store genetic information and catalyze reactions makes it a compelling candidate for an ancient, simpler precursor to DNA. If life indeed began with an RNA-based system, understanding whether RNA had a preference for left-handed amino acids could illuminate why homochirality arose. Surprisingly, the new study found that RNA does not inherently favor the left-handed orientation of amino acids, challenging the idea that life’s bias for left-handedness is rooted in the earliest stages of molecular evolution.
Researchers from the University of California, Los Angeles, led by Irene Chen, conducted experiments using specialized RNA molecules called ribozymes. Ribozymes are RNA sequences that can catalyze chemical reactions, similar to protein enzymes, and are thought to have been critical in early biochemistry. The team simulated conditions that might have existed on early Earth, exposing ribozymes to amino acid precursors under various environmental settings. The results demonstrated that ribozymes did not exhibit a consistent preference for left- or right-handed amino acids. Instead, they showed that RNA can support the synthesis of both orientations, undermining the hypothesis that early RNA chemistry dictated the homochirality seen in today’s biological proteins.
Chen’s team examined 15 different combinations of ribozymes and amino acid precursors, focusing on the amino acid phenylalanine. They found that RNA-based chemistry could yield either left- or right-handed phenylalanine, indicating that early RNA might have operated in a chemically neutral environment regarding chirality. This neutrality suggests that life’s consistent use of left-handed amino acids likely resulted from later evolutionary processes rather than an inherent chemical property of RNA.
Co-author Alberto Vázquez-Salazar noted that the findings imply life’s homochirality was not a consequence of initial chemical determinism but may have developed due to evolutionary pressures. This opens the possibility that external factors, such as environmental changes or the influence of specific molecular interactions over time, shaped the consistent left-handed bias in amino acids as life evolved.
The implications of this study extend beyond Earth’s history, reaching into the search for extraterrestrial life. Since life on Earth settled on one chiral direction, understanding whether this preference is universal or unique to our planet can help guide the hunt for life beyond Earth. During the early history of our planet, the evidence for prebiotic chemistry is mostly lost due to geological activity. Earth’s dynamic crust, driven by plate tectonics, has erased much of the evidence from the earliest stages of life. Scientists believe that asteroids or meteorites might have delivered essential organic compounds, including amino acids, to the young Earth. Similar processes could have played a role in shaping life’s molecular evolution.
To explore these possibilities, researchers are not only conducting chemical experiments on Earth but also analyzing extraterrestrial materials. Jason Dworkin, a senior astrobiology scientist at NASA’s Goddard Space Flight Center, highlighted the importance of studying the chirality of amino acids found in meteorites and asteroids. Dworkin, a co-author of the study, is involved in NASA’s OSIRIS-REx mission, which collected samples from the asteroid Bennu. These samples, recently returned to Earth, are undergoing detailed analysis to investigate the handedness of their amino acids. The results could offer clues about whether the chiral bias seen on Earth has a cosmic counterpart.
In the future, missions to Mars and other celestial bodies may include similar experiments to search for evidence of ancient or existing life. By testing for chirality and the presence of molecules like ribozymes and proteins, scientists aim to determine if life elsewhere shares the same molecular preferences or exhibits a different chiral bias. Such discoveries could reshape our understanding of life’s potential diversity across the universe.
Ultimately, the study conducted by Chen and her team has deepened one of the most intriguing mysteries in biology: why does life on Earth favor left-handed amino acids? The new evidence suggests that this preference is not rooted in the earliest chemistry of life but may have emerged due to the evolutionary dynamics of a complex and changing environment. The findings push scientists to look beyond simple chemical explanations and consider a broader set of influences, from environmental pressures to cosmic factors, in the search for the origins of life’s unique molecular asymmetry.