29 August 2021

Quanta Magazine: “DNA has Four Bases. Some Viruses swap in a Fifth”

Researchers have long been intrigued by the possibility that evolution could have gone in a different direction with DNA’s four bases: adenine (A), thymine (T), cytosine (C) and guanine (G). Perhaps there could have been more than four of them, or they could have had very different chemical or binding properties, or they could have used a different set of rules to represent information. Synthetic biologists like Romesberg have explored this by engineering artificial base pairs and additional amino acids to produce novel proteins. Even so, because an organism’s survival depends on keeping its genetic alphabet and code intact, the precise ingredients in DNA’s recipe are thought to have been largely locked in by evolution for billions of years — making them “frozen accidents”, in the words of Francis Crick.

But some exceptions have cropped up. 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.

Jordana Cepelewicz

Fascinating! The new development is that recently scientists have discovered this Z substitution in more than 200 phages, taking it from a singular occurrence to something that may happen regularly in nature under evolutionary pressure. Evidently there is much more to learn about molecular biology and perhaps the emergence and development of life: DNA is believed to have existed in its current form for billions of years, but this piece of evidence shows that, at least for viruses, that may not be entirely the case.

Figure showing how Z-T pairings differ from A-T pairings in viral DNA
Alternative DNA for viruses Samuel Velasco/Quanta Magazine; source: nature

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