The evolutionary history of prosaposin: Two successive tandem-duplication events gave rise to the four saposin domains in vertebrates

Prosaposin is a multi functional protein encoded by a single-copy gene. It contains four saposin domains (A. B, C. and D) occurring as tandem repeats connected by linker sequences. Because the saposin domains are similar to o ne another. it is deduced that they were created by sequential duplications of an ancestral domain. There are two types of evolutionary scenarios that may explain the creation of the four-domain gene: (1) two rounds of tandem internal gene duplication and (2) three rounds of duplications. An evoluti onary and phylogenetic analysis of saposin DNA and amino acid sequences fro m human, mouse. rat, chicken, and zebrafish indicates that the first evolut ionary scenario is the most likely. Accordingly, an ancestral saposin-unit duplication produced a two-domain gene, which. subsequently, underwent a se cond complete tandem duplication to give rise to the present four-domain st ructure of the prosaposin gene.