Independent evolution of heavy metal-associated domains in copper chaperones and copper-transporting ATPases

Copper chaperones are small cytoplasmic proteins that bind intracellular co pper (Cu) and deliver it to Cu-dependent enzymes such as cytochrome oxidase , superoxide dismutase, and amine oxidase. Copper chaperones are similar in sequence and structure to the Cu-binding heavy metal-associated (HMA) doma ins of Cu-transporting ATPases (Cu-ATPases), and the genes for copper chape rones and Cu-ATPases are often located in the same operon. Phylogenetic ana lysis shows that Cu chaperones and I-IMA domains of Cu-ATPases represent an cient and distinct lineages that have evolved largely independently since t heir initial separation. Copper chaperone-Cu-ATPase operons appear to have evolved independently in different prokaryotic lineages, probably due to a strong selective pressure for coexpression of these genes.