Expression of Type II Chorionic Gonadotropin Genes Supports a Role in the Male Reproductive System

Abstract

Human chorionic gonadotropin (hCG) is a glycoprotein hormone essential to pregnancy. hCG is heterodimeric and functionally defined by its β subunit. hCGβ evolved from the β subunit of luteinizing hormone in two phases. In the first phase, type I genes (hCGβ3, -5, -7, and -8) acquired changes affecting gene expression and extending the proteins' C terminus. In the second phase, type II genes (hCGβ1 and -2) were formed by the insertion of a DNA element into the type I 5' end. The insertion includes the small noncoding RNA gene snaR-G and has been predicted to drastically change the protein products encoded. We trace the insertion to the common ancestor of the African great apes and show that it contains transcription signals, including snaR-G. Type II transcripts are predominantly expressed in testis. Contrary to predictions, the product of the major mRNA splice form is hCGβ. A novel peptide is encoded by alternatively spliced transcripts. These findings support the view that type II genes evolved in African great apes to function in the male reproductive system.