But the biggest surprise is that the virus has a polymerase dedicated to pairing the Z base with the T base during DNA replication. “It’s like a fairy tale,” said Marlière, who had been hoping to find such a polymerase. “Our wildest dream has come true.”
This is because although scientists have found other examples of bacteriophages performing nucleotide substitutions, this is “the first polymerase that truly shows the selective exclusion of canonical nucleotides,” New England Biolabs studied non-canonical bases. Said Peter Wigler, a researcher in base biosynthesis. The system evolved to allow “reprogramming,” Romesberg said-this may provide new insights into the function of polymerases and how to design them.
Z and other modified DNA bases seem to have evolved to help viruses evade bacteria from degrading foreign genetic material. Romesberg said that the eternal arms race between bacteriophages and their host cells may provide enough selective pressure to affect things that seem “sacred and inviolable” like DNA. “Now, everyone thinks that these modifications are just protecting DNA,” he said. “People almost despise it.”
But more things may be at work: for example, the triple bond of Z may increase the stability and rigidity of DNA, and may affect some of its other physical properties. The possible advantages of these changes are not only to evade bacterial defenses, but also may make such modifications have broader significance.
After all, no one really knows how many viruses might play with their DNA like this. “standard [genome sequencing] The way to find biodiversity in nature will not be able to find these,” said Steven Banner, A chemist at the Applied Molecular Evolution Foundation of Florida, who synthesized several artificial base pairs, “because we are looking for a common biochemical method that assumes no existence.”
These neglected alternatives may even appear not only in the virus. “Maybe we missed something in the bacterial world, right?” said Chuan He, A chemical biologist at the University of Chicago.
Synthetic biology (again) shows that this is possible.Over the years, Marlière’s team has been developing Escherichia coli Use modified bases instead of T nucleotides. Huimin Zhao, A chemist at the University of Illinois at Urbana-Champaign and some recent leaders in Z genome work, are trying to obtain Escherichia coli And other cells that may incorporate Z like a virus.
Romesberg believes that these findings may raise questions about bacterial DNA modifications, which are thought to be epigenetic—that is, changes in nucleotides after DNA synthesis usually affect gene expression. He said that the Z substitution “shows that what you might think is epigenetic might not be.”
“I think people need to look under rocks that are considered understandable,” he added. “This is the source of the surprise.”
But there is also a lot of room for surprises in places with less research, because “we can’t cultivate most of the microorganisms on earth,” says Carol Clayland, A philosopher of science at the University of Colorado at Boulder. “Anything else we can’t recognize?”
For example, Marlière wants to know whether scientists will one day stumble upon more than one base modification in a single genome. Or they may find that the molecular skeleton of DNA has changed. In this case, “it is no longer DNA,” he said. “That would be something else.”
We need to “stop taking the components of molecular biology for granted,” Freeland said. “Purely because our instruments have become better, we seem to work harder, and we think that everything that is standard and common is gradually disappearing.”
ability Reprinted with authorization Quanta Magazine, Edit independent publications Simmons Foundation Its mission is to improve the public’s understanding of science by covering research developments and trends in mathematics, physics, and life sciences.
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