In a world of microbial warfare, you sometimes have to change the very substance of who you are.
Viruses that infect bacteria – aptly called bacteriophages – and their prey have been at war for ages, with each side developing more diabolical tactics to infect or destroy each other. Eventually, some bacteriophages took this arms race to a new level by changing the way they encode their DNA.
At least that’s what we think happened. Once considered an outlier, new research published in three separate papers shows that there is an entire army of bacteriophages with non-standard DNA, which researchers call a Z genome.
“Genomic DNA consists of four standard nucleotides … These nucleobases form the genetic alphabet, ATCG, which is conserved across all domains of life,”
“In 1977, however, the DNA virus cyanophage S-2L was discovered with all occurrences of ‘A’ substituted with 2-aminoadenine (Z) throughout its genome and formed the genetic alphabet ZTCG.”
The reason seemed to be self-protection. Within the compound ‘step’ of a DNA double helix, the ‘Z’ base forms a triple bond to the opposite ‘T’ base, one more than the two bonds of the common A: T compound. This makes the virus genome harder and harder for bacteria to dispense with chemicals called nucleases.
Although researchers were fascinated, no other bacteriophages with the Z genome were found, and with the difficulty of culturing S-2L in a laboratory, the Z genome was deposited as a curiosity.
Now, research documented in three separate studies from researchers in France and China shows that this was not a one-time venture, while also characterizing how the Z genome works and how it is assembled.
“Scientists have long dreamed of increasing the diversity of bases. Our work shows that nature has already come up with a way to do it,” wrote one of the teams, led by first author Yan Zhou of Tianjin University, in their paper.
Zhou’s team along with another group led by Institute Pasteur microbiologist Dona Sleiman found two major proteins, which they called PurZ and PurB; these form the ‘Z’ base.
A third group, led by Université Paris-Saclay synthetic biologist Valerie Pezo, confirmed these findings and analyzed an enzyme – called DpoZ – which is responsible for assembling the entire Z genome.
All three searched genetic sequence databases for the sequences related to their proteins and enzymes and found a large number of bacteriophages with similar genes.
“[The authors] has done an incredibly extensive job of showing that this is not a crazy outlier, but there is a whole group of bacteriophages who have this kind of genetic material, “Jef Boeke, a molecular biologist at New York University who was not involved in the work , told The scientist.
There are still plenty of questions to answer on the Z genome.
For example, is a Z genome compatible with regular cell machines like ours? And could it be used in the same way that artificial DNA begins to be?
“The Z base is uniquely identified in a carbonaceous meteorite and proposed as a nucleobase that could have been available for the origin of life,” the team leader of Zhou wrote in their paper.
“Given that the Z-base was discovered in a meteorite, our work may arouse interest in interdisciplinary research on the origin and astrobiology of life.”
The three articles are published in Science here, here and here.