Ancient origin of placental expression in the growth hormone genes of anthropoid primates

In anthropoid primates, growth hormone (GH) genes have undergone at least 2 independent locus expansions, one in platyrrhines (New World monkeys) and another in catarrhines (Old World monkeys and apes). In catarrhines, the GH cluster has a pituitaryexpressed gene called GH1; the remaining GH genes include placental GHs and placental lactogens. Here, we provide cDNA sequence evidence that the platyrrhine GH cluster also includes at least 3 placenta expressed genes and phylogenetic evidence that placenta expressed anthropoid GH genes have undergone strong adaptive evolution, whereas pituitary-expressed GH genes have faced strict functional constraint. Our phylogenetic evidence also points to lineage-specific gene gain and loss in early placental mammalian evolution, with at least three copies of the GH gene present at the time of the last common ancestor (LCA) of primates, rodents, and laurasiatherians. Anthropoid primates and laurasiatherians share gene descendants of one of these three copies, whereas rodents and strepsirrhine primates each maintain a separate copy. Eight of the amino-acid replacements that occurred on the lineage leading to the LCA of extant anthropoids have been implicated in GH signaling at the maternal-fetal interface. Thus, placental expression of GH may have preceded the separate series of GH gene duplications that occurred in catarrhines and platyrrhines (i.e., the roles played by placenta-expressed GHs in human pregnancy may have a longer evolutionary history than previously appreciated).Organismic and Evolutionary Biolog