Endocrinology, Vol 112, 482-485, Copyright © 1983 by Endocrine Society

ARTICLES

Difference in sizes of human compared to murine alpha-subunits of the glycoprotein hormones arises by four-codon gene deletion or insertion

WW Chin, JV Maizel Jr and JF Habener

The sizes of the human and subhuman alpha-subunits of the glycoprotein hormones differ by four amino acids (hCG alpha, 92 amino acids; murine, equine, bovine, and ovine alpha, 96 amino acids). The shortening of the human alpha-subunit has been attributed to posttranslational proteolysis. We have recently determined the nucleotide sequences of the mRNAs encoding the precursors of the alpha-subunit of mouse TSH and rat gonadotropins using recombinant DNA techniques. In this report, we have compared these nucleotide sequences and their deduced amino acid sequences with those of the pre- alpha-subunit of hCG (hCG pre-alpha) and the gene encoding the human alpha-subunit. We show that the difference in size of four amino acids between the apoproteins of the murine and human alpha-subunits is a result of a deletion, or insertion, of four codons close to the site of the second intron in the human gene. In addition, the sequence of four codons absent in the mRNA encoding hCG pre-alpha is similar to a region in the 3' end of this intron. These findings indicate that the differences in size of these alpha-subunits originate at the gene level rather than at the posttranslational level at which proteolytic processing occurs.