Some bacteria-killing viruses spell out their genetic instructions in a different DNA alphabet.
More than 40 years ago, scientists in Russia reported that a type of bacteriophage called cyanophage S-2L replaces the DNA building block adenine, commonly known as A, with 2-aminoadenine, designated Z. But no one knew how the phage went from A to Z, or why.
In the 1990s, Philippe Marlière, a xenobiologist then at the Pasteur Institute in Paris, was “looking for examples divergent from life as we know it,” when he came across the 1977 Russian study describing the cyanophage with the unusual DNA. After getting a sample of the virus, Marlière and colleagues deciphered the phage’s complete set of genetic instructions, or genome.
In the virus’s genome, the researchers found instructions for building an enzyme, called PurZ, that could carry out the first step in making Z — also known as diaminopurine. The Pasteur Institute filed a patent on the enzyme in Marlière’s name in 2003.
With the enzyme in hand, “it became crystal clear how Z was made, but we didn’t [do] any experiments to prove that we were right,” says Marlière, now president of the European Syndicate of Synthetic Scientists and Industrialists in Berlin. The project was halted for a variety of reasons.
The researchers didn’t publish their findings until now, in part, because PurZ wasn’t the enzyme Marlière was looking for. Instead, he says he had hoped to find a different enzyme, a polymerase that would reject adenine and instead build DNA with Z in its place. “I was very, very disappointed,” he says, “because the polymerase I was craving could not be detected in that phage.”
More than 40 years ago, scientists in Russia reported that a type of bacteriophage called cyanophage S-2L replaces the DNA building block adenine, commonly known as A, with 2-aminoadenine, designated Z. But no one knew how the phage went from A to Z, or why.
In the 1990s, Philippe Marlière, a xenobiologist then at the Pasteur Institute in Paris, was “looking for examples divergent from life as we know it,” when he came across the 1977 Russian study describing the cyanophage with the unusual DNA. After getting a sample of the virus, Marlière and colleagues deciphered the phage’s complete set of genetic instructions, or genome.
In the virus’s genome, the researchers found instructions for building an enzyme, called PurZ, that could carry out the first step in making Z — also known as diaminopurine. The Pasteur Institute filed a patent on the enzyme in Marlière’s name in 2003.
With the enzyme in hand, “it became crystal clear how Z was made, but we didn’t [do] any experiments to prove that we were right,” says Marlière, now president of the European Syndicate of Synthetic Scientists and Industrialists in Berlin. The project was halted for a variety of reasons.
The researchers didn’t publish their findings until now, in part, because PurZ wasn’t the enzyme Marlière was looking for. Instead, he says he had hoped to find a different enzyme, a polymerase that would reject adenine and instead build DNA with Z in its place. “I was very, very disappointed,” he says, “because the polymerase I was craving could not be detected in that phage.”
