The cDNA for the β-subunit of human chorionic gonadotropin suggests evolution of a gene by readthrough into the 3′-untranslated region

Abstract

A 579 base pair approximately full-length c[complementary]DNA which codes for the 145-amino acid long .beta.-subunit of human chorionic gonadotropin (HCG) was cloned in the plasmid vector pBR322 and its complete nucleotide sequence determined. A hydrophobic presequence of 20 amino acids can be identified from the nucleotide sequence. The amino acid sequence of the .beta.-subunit is related to those of the .beta.-subunits of the other glycoprotein hormones LH [luteinizing hormone], FSH [follicle stimulating hormone] and TSH [thyroid stimulating hormone] but the .beta.-subunit of HCG is unique in that it contains a C-terminal extension of about 30 amino acids which has no homologous counterpart in the other 3 hormones. Analysis of the .beta.HCG cDNA nucleotide sequence suggests that this extension may have arisen by the loss of the termination codon of an ancestral .beta.-like gene so that most of what was previously the 3''-untranslated region now codes for protein. The .beta.-subunit of HCG terminates with the codon UAA located 16 bases before the poly(A) in the sequence AAUAAA. This sequence is believed to be a recognition signal involved in either polyadenylation or processing and therefore has a dual role in this gene, serving both a coding and a regulatory function.