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But the biggest surprise was that the virus had a polymerase enzyme dedicated to pairing Z bases with T during DNA replication. “It was like a fairy tale,” Marlière said, hoping to find such a polymerase. “Our wildest dreams came true.”
That’s because scientists have found other examples of bacteriophages that make nucleotide substitutions, but this is “the first polymerase to be shown to selectively exclude a canonical nucleotide,” said New England Biolabs researcher Peter Weigele, who studies the biosynthesis of non-canonical bases. The system allowed for “a reprogramming,” Romesberg said, that could provide new insights into how polymers work and how to design them.
Z and other DNA bases appear to have evolved to help prevent viruses from defending themselves against bacteria that degrade foreign genetic material. According to Romesberg, according to Romesberg, the perpetual weapon race between bacteriophages and their host cells puts enough selection pressure to cause something as seemingly “sacrosanct” as DNA. “Right now, everyone believes that changes protect DNA,” he said. “People are almost frustrated.”
But there may be something more at work: the triple binding of Z, for example, can add to the stability and rigidity of DNA and can affect its other physical properties. These changes can be beneficial in addition to hiding from bacterial defenses, and these changes can be more significant.
After all, no one knows how many viruses have played with such DNA. “Standard [genome sequencing] methods of seeking biological diversity in nature would not find them, ”he said Steven Benner, A chemist at the Florida Foundation for Applied Molecular Evolution, who has synthesized several pairs of artificial bases, “because we’re looking for it in a way that assumes ordinary biochemistry that isn’t present.”
These types of unforgettable substitutions can cause more viruses. “Maybe we lost some of them in the world of bacteria, right?” he said Chuan He, Chemical biologist at the University of Chicago.
Synthetic biology has (again) shown that this is possible. Marlière’s team has been evolving for years E. coli Those that use a modified base instead of T nucleotides. Huimin Zhao, A chemist at the University of Illinois, Urbana-Champaign and leader of some recent Z genome work, is trying to get E. coli and perhaps other cells like Z viruses.
Romesberg believes that these findings may cast doubt on changes in the DNA of bacteria that were thought to be epigenetic, that is, changes in nucleotides after DNA synthesis, usually affecting gene expression. The Z substitution, he says, “shows that things that might have been thought to be epigenetic may not be.”
“I think people need to look under the stones in a way that they can understand,” he added. “That’s where the surprises come from.”
There are also a lot of unpredictable places in places that are so well studied, because “we can’t treat most of the Earth’s microbes,” he said. Carol Cleland, A philosopher of science at the University of Colorado, Boulder. “Are there any other things we don’t know?”
Marlière wonders, for example, whether scientists will one day find more than one type of base change in a single genome. Or they may find a change in the molecular backbone of DNA, in which case “it would no longer be DNA,” he said. “It would be something else.”
Freeland said, “We need to stop taking the components of molecular biology as we know them.” “Because our equipment has improved and we’ve looked harder, everything we thought was standard and universal is falling apart.”
Original story reprint with permission Quanta magazine, independent publication of the editorial Simons Foundation its mission is to improve public knowledge of science by covering developments and trends in research in mathematics and the physical and physical sciences of life.
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