Today, RNA might seem less significant when contrasted with its flashier relative, DNA, yet many scientists posit that RNA molecules were integral to the genesis of life. Due to their capacity for storing genetic information and self-propagation, they potentially initiated the evolutionary trajectory leading to increasingly complex life forms.
To date, researchers hadn’t managed to discover RNA molecules capable of self-replication—a mandatory attribute of living things. However, they are now very close to achieving this. In a report published in the journal Science, investigators detail the creation of RNA strands that can generate a mirror image of themselves and then employ that template to construct the original.
A single RNA molecule cannot yet complete the entire cycle, but the researchers maintain that this breakthrough significantly bolsters the theory of RNA as life’s evolutionary precursor. “These are very strong findings,” states Gerald Joyce of the Salk Institute for Biological Studies and a pioneer of the “RNA world” hypothesis.
He and other researchers were drawn to RNA because, even presently, the molecule handles two functions vital to organisms. It encodes hereditary data within the order of its chemical subunits, known as nucleotide bases. Furthermore, the rigid three-dimensional structures it folds into can execute a second crucial task: acting as catalysts to facilitate essential chemical reactions without being consumed in the process. For many investigators, this dual capability positioned RNA as a prime candidate for life’s initial trigger, having the power both to code its own makeup and to catalyze its own multiplication.
In 1993, after generating and testing vast libraries comprising trillions of distinct RNA types, researchers guided by Jack Szostak and David Bartel identified those capable of performing certain necessary operations. Then, in 2009, Joyce and his team isolated two different RNA molecules capable of synthesizing each other.
Nevertheless, these could not self-replicate, and at sizes exceeding 150 to 200 bases, they were too large to have arisen spontaneously from early Earth compounds. “They can’t emerge from the primordial soup,” notes Joyce. Moreover, at that size, they would likely degrade before full synthesis could be achieved. Conversely, the newly engineered versions are roughly three times smaller, making their unsolicited emergence at least plausible. “That’s a major advance,” Joyce comments.
To mitigate breakdown, biochemists Edoardo Gianni and Philippe Holliger, along with their group at the University of Cambridge, conducted experiments under low-temperature regimes. They theorized that reduced temperatures would not only slow down the processes leading to RNA degradation but also potentially aid the RNA copying mechanism. As water begins to freeze, it excludes other substances from growing ice crystals, thereby concentrating nucleotides, salts, and other vital building blocks for RNA synthesis within minute, fluid-filled channels. These confined spaces also feature less liquid water, which actually accelerates RNA degradation, Holliger explains.
When RNA is placed in a freezing solution mixed with individual nucleotides, the majority of RNA strands remain folded—the configuration required for them to function as catalysts. However, to serve as a template for duplication, these RNA molecules must be unfolded. Earlier studies suggested a strategy of incorporating nucleotide triplets that could help keep the template strand in its open conformation. After testing nearly one trillion different random RNA sequences within the freezing mixture, the team found that the inclusion of both solitary bases and triplets allowed some RNA strands to fold up and act catalytically, while others remained extended and available for copying.
The team successfully identified three RNA molecules, each approximately 45 bases long, capable of copying themselves onto complementary templates. The RNA species could also take the subsequent step, starting from the templates and regenerating the original molecules. Evidence is currently lacking that a single RNA molecule can perform both reactions sequentially, synthesizing its complement and then using that complement to synthesize itself. Furthermore, the cold conditions meant that generating new RNA strands took about 72 days. However, life may indeed have begun in the cold: many researchers investigating life’s origins suggest that natural freeze-thaw cycles on Earth could have facilitated the concentration of life’s basic components.
“The immediate next step is to determine if this system, or one like it, can be made robust enough to actually observe repeating cycles of replication,” says Szostak. Should this occur, RNA could transition from being a possible origin of life to a probable one.
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