A widespread pathway for substitution of adenine by diaminopurine in phage genomes

<jats:title>Biosynthesis and replication, from A to Z</jats:title> <jats:p> Four nucleobases. adenine (A), cytosine (C), guanine (G), and thymine (T), are usually thought to be invariable in DNA. In bacterial viruses, however, each of the DNA bases have variations that help them to escape degradation by bacterial restriction enzymes. In the genome of cyanophage S-2L, A is completely replaced by diaminopurine (Z), which forms three hydrogen bonds with T and thus creates non–Watson-Crick base pairing in the DNA of this virus (see the Perspective by Grome and Isaacs). Zhou <jats:italic>et al.</jats:italic> and Sleiman <jats:italic>et al.</jats:italic> determined the biochemical pathway that produces Z, which revealed more Z genomes in viruses hosted in bacteria distributed widely in the environment and phylogeny. Pezo <jats:italic>et al.</jats:italic> identified a DNA polymerase that incorporates Z into DNA while rejecting A. These findings enrich our understanding of biodiversity and expand the genetic palette for synthetic biology. </jats:p> <jats:p> <jats:italic>Science</jats:italic> , this issue p. <jats:related-article issue="6541" page="512" related-article-type="in-this-issue" vol="372">512</jats:related-article> , <jats:related-article issue="6541" page="516" related-article-type="in-this-issue" vol="372">516</jats:related-article> , <jats:related-article issue="6541" page="520" related-article-type="in-this-issue" vol="372">520</jats:related-article> ; see also p. <jats:related-article issue="6541" page="460" related-article-type="in-this-issue" vol="372">460</jats:related-article> </jats:p>