Abstract
Secretoglobins (SCGBs) are a superfamily of small, dimeric, cytokine-like proteins found originally in the reproductive tracts and airways of mammals. Most SCGB research has focused on respiratory diseases in humans and laboratory animal models but knowledge of their biological functions is sparse. We report here a broad survey of Scgbs, the genes that encode SCGBs, in animal genomes. We tested the view that they are uniquely mammalian in origin and distribution, hoping that understanding their distribution would shed light on their evolutionary history and perhaps point to putative biological functions. Rather than being uniquely mammalian, we found many different SCGBs in turtles, crocodilians, lizards, and birds, suggesting they existed in the Carboniferous Period (∼320 MYA) when the sauropsids evolved in the amniote lineage. We identified no SCGBs in amphibians or fishes, suggesting that this characteristic originated in an amniote ancestor. Amniotes include sauropsid and synapsid lineages, and three subfamilies of SCGBs (SCGB2A, SCGB3A, and SCGB1C) are found in both sauropsid and synapsid lineages. Uteroglobin (SCGB1A), the first identified SCGB protein, is uniquely mammalian, having appeared in monotremes. The SCGB subfamilies including androgen-binding proteins (SCGB1B and SCGB2B) are first seen in metatherians. This complex distribution suggests that there is an as-yet-undiscovered basic function of SCGBs shared by all amniotes.