Phylogenetic relationships within the AID/APOBEC gene family. The neighbor-joining tree shown here is generated from a protein alignment of the exon encoding the zinc-coordinating motif (the alignment is provided as Additional data file 1). The position of the agnathan (sea lamprey) AID (indicated by the arrow), separated from the clade comprising all the other AID/APOBECs, could suggest that all family members have originated from the ancestral AID. The different clusters in the AID/APOBEC family are identified, with the APOBEC3 cluster further divided into Z1a, Z1b, and Z2 clades (for the nomenclature of the APOBEC3 subgroups see ). Each domain of the double-domained APOBEC3s is included individually, with the amino-terminal and carboxy-terminal domains labeled [N] and [C], respectively. While APOBEC1 has been described only in mammals, the APOBEC2 group is found in all jawed vertebrates, including the primitive ghost shark. The duplication of the APOBEC2 locus after an ancient genome duplication in bony fish has been maintained, resulting in two coevolving APOBEC2 genes. The organisms in which each group is found are indicated below the clade label. Clades are collapsed for clarity, and only nodes with a bootstrap value greater than 50 are shown. The sequences used are either described in [10,12] or obtained from the Ensembl Genome Browser . The sequences for the ghost shark were obtained using the AID/APOBECs as queries in BLAST searches on the Callorhinchus milii genome shotgun contigs (GenBank accession numbers: AID, AAVX01329030; APOBEC2, AAVX01039499; APOBEC4, AAVX01642881).