Genome complexity: Z-DNA a new layer of complexity (Introduction)

by David Turell , Monday, July 12, 2021, 18:32 (1018 days ago) @ David Turell

Another review:

https://www.quantamagazine.org/dna-has-four-bases-some-viruses-swap-in-a-fifth-20210712/

"A few decades ago, researchers found viruses that had swapped one of the four bases in their DNA for a novel fifth one. Now, in a trio of papers published in Science in April, three teams have identified dozens of other viruses that make this substitution, as well as the mechanisms that make it possible. The discoveries raise the thought-provoking possibility that this kind of fundamental genomic change could be much more widespread and important in biology than anyone imagined.

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"In 1977, for instance, researchers in the Soviet Union found something peculiar while looking at a virus that infects photosynthetic bacteria: All the A’s in the genome had been replaced with an alternative base, 2-aminoadenine, which was later dubbed Z. Usually, C pairs with G and T pairs with A to form double-stranded DNA. But in this virus, with no A’s to be found, T paired with Z. (During gene transcription, T-Z was still treated as though it were T-A.)

"The Z base looks like a chemical modification of A; it’s an adenine nucleotide with an extra attachment. But that modest change allows Z to form a triple hydrogen bond with T, which is more stable than the double bond that holds together A-T.

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"The scientists have now reported finding the Z substitution in more than 200 phages. Further analysis of the viral genomes allowed the research groups to uncover a key enzyme for making Z, as well as an enzyme that degrades free-floating A nucleotides, making Z more likely to be taken up during DNA synthesis.

"But the biggest surprise was that the viruses had a polymerase enzyme dedicated to pairing Z bases with T’s during DNA replication. “It was like a fairy tale,” said Marlière, who had been hoping to find such a polymerase. “Our wildest dreams came true.” (my bold)

"That’s because while scientists have uncovered other examples of bacteriophages making nucleotide substitutions, this “is the first polymerase that is really shown to selectively exclude a canonical nucleotide,” said Peter Weigele, a researcher at New England Biolabs who studies the biosynthesis of noncanonical bases. The system evolved to allow “a reprogramming,” Romesberg said — one that could potentially provide new insights into how polymerases function, and how to engineer them.

"Z and other modified DNA bases seem to have evolved to help viruses evade the defenses with which bacteria degrade foreign genetic material. The eternal arms race between bacteriophages and their host cells probably provides enough selection pressure to affect something as seemingly “sacrosanct” as DNA, according to Romesberg. “Right now, everyone thinks the modifications are just protecting the DNA,” he said. “People almost trivialize it.”

"But something more may be at work: The triple bond of Z, for instance, might add to DNA’s stability and rigidity, and perhaps influence some of its other physical properties. Those changes could carry advantages beyond hiding from bacterial defenses and could make such modifications more broadly significant.

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"We need to “stop taking the components of molecular biology as we know them for granted,” Freeland said. “Purely because our instrumentation has gotten better and we’ve looked harder, everything that we thought was standard and universal is just falling away.'”

Comment: This really adds to our knowledge of this new style DNA. That a special enzyme must be produced to create the Z base brings the issue of design to the fore, as my bold above shows. Remember enzymes support reactions by having stations for the reacting molecules, literally forcing them to react. T his required the design of huge molecules made up of thousands of amino acids in special sequences, not happening by chance. This also relates to Shapiro's discovery that bacteria DNA. He never discovered how they do it. Again, enzymes?

The last comment by the author is important. We do not know what we do not yet know, and conclusions are not in cement. Known genome complexity will vastly increase with time, and it will require a designer.