Gene content and coding diversity of growth hormone loci of apes

Abstract Growth hormone (GH) locus experienced dramatic evolution in primates, becoming multigenic and diverse in anthropoids. Despite sequence information from vast number of primate species, it has remained unclear how the multigene family was favored feature. We sought to compare the structure and composition of the apes’ GH loci as a prerequisite to understanding their origin and possible evolutionary role. GH loci of chimpanzee, gorilla, and orangutan were sequenced from bacterial artificial chromosomes, while those of modern man, neanderthal, gibbon, and wild boar were retrieved from GenBank. Coding regions, regulatory elements, and repetitive sequences were identified and compared among species. GH loci of all analyzed species are flanked by the genes CD79B (5´) and ICAM-1(3´). In man, neanderthal, and chimpanzee the loci are integrated by five genes almost indistinguishable, however while in the former two they render three different hormones, in the latter one four different proteins are derived. Gorilla exhibits six genes, gibbon seven, and orangutan four. The sequences of proximal promoters, enhancers, P-elements, and a locus control region (LCR) are highly conserved. The locus evolution might have implicated duplications of the ancestral pituitary GH-N gene and subsequent diversification of the copies, to lead to the placental single GH-V gene and to the multiple also placental CSH genes.