Another Genetic “Letter” Found in Viruses

The biochemical synthesis of the new nitrogenous base is not simply done by adding the amino group to the carbon. Instead, it was recently shown by Sleiman’s team that the synthesis of Diaminopurine occurs via a parallel pathway to that of Adenine synthesis, by using the enzyme PurZ (named because it is involved in the synthesis of the Purine Z/Diaminopurine). Adenine biosynthesis, alternatively, begins with the PurA enzyme. The products of both enzymes are then acted on by the enzyme PurB. After the step involving PurB, various other reactions occur, eventually resulting in a free nucleotide (dAMP or dZMP) that can then be inserted into the DNA during replication (Sleiman et al., 2021).
In the past, researchers have confirmed that viral DNA polymerases can recognize and use Diaminopurine, but they do not differentiate between using it and Adenine. Since the DNA found in these viruses contains entirely Diaminopurine and no Adenine, there must be some polymerase that preferentially selects the former over the latter. In exploring this idea, an additional team of researchers working with those who discovered PurZ found such a polymerase – and called it DpoZ (named because it is a DNA Polymerase that has selectivity for Diaminopurine/Z) (Pezo et al., 2021).

Two papers from this same team detailed the evolutionary route of the DpoZ and PurZ; the researchers demonstrated that both enzymes are found in many different kinds of bacteriophages (viruses that infect bacteria), especially those in the Podoviridae and Siphoviridae families. Additionally, they showed that the two enzymes evolved in tandem and possibly originated around 3.5 billion years ago. The researchers theorized that the enzymes likely evolved after some duplication of their adenine-favoring counterparts due to the homology between the two sets of genes (Pezo et al., 2021; Zhou et al., 2021).

The Z nucleotide is not the first modified base to be found in DNA; many organisms, including humans, add a chemical tag called a methyl group to cytosine bases to form 5-Methylcytosine, which is used to regulate the expression of genes. This methylation reduces gene expression (Bailly & Waring, 1998). Even in viral DNA, other modified bases exist. Various methylated bases can provide the virus a “memory” of its recent hosts. Additionally, various other chemical groups can be added onto the four basic nucleotides in viruses to serve a variety of purposes (Weigele & Raleigh, 2016). However, Diaminopurine is the first modified base that has been detected that (1) alters the amount of hydrogen bonds in the base pair and (2) originates not from simple modification of a pre-existing base but from its own biosynthetic pathway (Pezo et al., 2021; Sleiman et al., 2021; Zhou et al., 2021).

Future research should be done on the existence of other PurZ and DpoZ homologs in viruses and other organisms to see if another unique base exists and is incorporated into their DNA. Additionally, research should explore the transcription and translation of the viral DNA into mRNA and protein within a host cell. It is likely that the increased hydrogen bonds between Diaminopurine and Thymine will also be present in the interaction between Diaminopurine and Uracil (the Thymine analog seen in RNA and the RNA and DNA of some viral genomes), possibly leading to a slowed or altered transcriptional process.