In 1977, scientists in St. Petersburg discovered a virus that was infecting cyanobacteria, a type of photosynthesizing bacteria, living in water on the outskirts of the city. The virus, cyanophage S-2L, had an adaptation that broke traditional rules of DNA construction and may open a whole new world of possibilities for synthetic biology.
Generally, DNA code is determined by the sequence of four different building blocks called nucleotides: adenine (A), thymine (T), guanine (G), and cytosine (C). The two strands of DNA that form the famous double helix are connected by pairs of these nucleotides, A to T and G to C. Yet these bonds are not equal in strength. Because of an additional hydrogen bond between the two, G has a slightly stronger connection to C than A does to T.
However, the cyanophage S-2L virus had all cases of A substituted with a modified version, 2-aminoadenine (Z), which contains one more nitrogen than the traditional A nucleotide. In this virus, Z pairs up with T, a pair that forms three bonds similar to the G:C pair. The additional strength from the Z:T pairings increases the overall stability of the virus’s DNA. But what is the functional benefit of this expansion of the genetic alphabet?
In aquatic environments, where this virus comes from, a virus must drift through the water until it happens to bump into a host. Having more stable DNA helps to prevent UV damage that could destroy a virus in the environment waiting to encounter a host. The increased stability could also protect the virus against host defenses, which often center around special enzymes called nucleases that are designed to break down DNA.
New research published in Science has identified how a combination of host and virus genes create the Z bases and prevent them from getting mixed up with A as virus DNA is assembled. Scientists think this system may have applications in expanding the range of tools used in synthetic biology, including new ‘designer proteins’ that may have therapeutic applications.
Interestingly, Z-DNA may be older than life itself! A 2011 analysis of a carbon-containing meteorite revealed standard and nonstandard DNA structures, including the Z base. If the Z base was formed in space, it may also have been formed in conditions on Earth at the time of the beginning of life.
For more information, read the full study published by Grome and Isaacs in Science.