Thota Kanishka Rao, Amity University Kolkata
A, C, T, and G are the four building blocks of DNA. However, some bacteriophage viruses use a particular DNA alphabet to encode their genetic instructions., i.e, exchange A for Z.
Scientists in Russia announced more than 40 years ago that cyanophage S-2L, a form of bacteriophage, replaces the DNA building block adenine, commonly known as A, with 2-aminoadenine, named Z. But no one understood how or why the phage went from A to Z.
According to researchers, a molecular and synthetic biologist at Yale University who co-authored a commentary in the same issue of Science, the findings have implications for the origins of life on Earth, the quest for life on other planets, and various future applications in biomedicine, synthetic biology, material sciences, and computing. The researchers discovered instructions for creating an enzyme called PurZ in the virus’s genome that could carry out the first step in the production of Z, also known as diaminopurine. In 2003, the Pasteur Institute applied for a patent on the enzyme in Marlière’s name. With the enzyme in hand, it had become crystal clear how Z was made said the researcher, there were no researches conducted to prove it.
This phage’s polymerase isn’t what he was hoping for. Marlière’s collaborator Pierre Alexandre Kaminski and colleagues discovered that cyanophage S-2L’s polymerase isn’t picky on whether it uses A or Z. Instead, another viral enzyme called DatZ degrades adenine building blocks, leaving the polymerase with no choice but to use Z.
The Siphoviridae bacteriophages, which infect a broad range of bacteria, all have versions of the polymerase called DpoZ that preferentially inject Z rather than A into the viruses’ DNA, according to the researchers. According to other researchers, the alternative alphabet can be used much more common than previously thought. They learned about the bacteriophages that use Z-containing DNA at a dinner party a few years ago. They scanned databases and discovered 60 bacteriophages that contain PurZ, including phages from both the Siphoviridae and Podoviridae families, unaware that the French scientists were still working on the puzzle. The team also discovered enzymes that degrade A as well as the biochemical pathway that phages use to make and integrate Z.
Even though the phages have enzymes, they do not always use Z in their DNA. Zhao and colleagues in China chose the phage SH-Ab 15497, which infects Acinetobacter bacteria, and verified that its DNA alphabet also has Z in place of A, according to their findings.
Instead of the two hydrogen bonds that hold A–T base pairs together, Z forms three hydrogen bonds with thymine. As a result, Z–T paired DNA is more stable and may be able to withstand hotter or harsher conditions than traditional DNA. With the added stability, one might wonder why Z isn’t used by all species on Earth. According to researchers, stability isn’t everything. To be copied, DNA must be unwound and broken apart. This could be more difficult with Z–T base pairs. Z often alters the way DNA curves and bends, possibly making it more difficult to cram into tight spaces as A-containing genetic material would.
This can make A more appealing to other species. Or maybe it was just a coincidence that A came first. Romesberg, a researcher in the same team, who has been working for years to get bacteria to integrate exotic DNA bases, says that if cells began using that base, so many things will have to shift to fully migrate to another base.
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Sources:
- Y. Zhou et al. A widespread pathway for substitution of adenine by diaminopurine in phage genomes. Science. Vol. 372, April 30, 2021, p. 512. doi: http://10.1126/science.abe4882.
- D. Sleiman et al. A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes. Science. Vol. 372, April 30, 2021, p. 516. doi: http://10.1126/science.abe6494.
- D. Czernecki et al. How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA. Nature Communications. Vol. 12, April 23, 2021. doi: http://10.1038/s41467-021-22626-x.
- M.W. Grome and F.J. Isaacs. ZTCG: Viruses expand the genetic alphabet. Science. Vol. 372, April 30, 2021, p. 460. doi: http://10.1126/science.abh3571.
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