Alpha-fetoprotein related gene (ARG): A new member of the albumin gene family that is no longer functional in primates

The serum albumin gene family is comprised of albumin, alpha-fetoprotein, alpha-albumin (afamin), and the more distantly related Vitamin D binding protein. These genes arose from a common ancestor through a series of duplication events, are expressed primarily in the liver and tightly linked in all species where this has been investigated. Here, we describe a fifth member of the albumin gene family that we have named Alpha-fetoprotein Related Gene (ARG) since it exhibits greatest similarity to this family member. ARG is activated in the liver perinatally, but is expressed at very low levels. The ARG gene is present and intact in the mouse, rat, dog and horse genomes. In contrast, the ARG gene in human, chimpanzee, rhesus monkey, and marmoset contains a number of mutations common to all four species, indicating that this gene has been an inactive pseudogene in primates for at least 40 million years. Low expression and aberrant splicing of the ARG gene in the mouse liver suggests that ARG may have less functional significance than other members of the serum albumin gene family even in species where it is still intact.