Structure of cloned DNA complementary to rat prolactin messenger RNA.

Prolactin (Prl), growth hormone (GH), and chorionic somatomammotropin (CS) form a set (the ‘Trl set”) of mammalian hormones which is thought to have evolved from a common ancestral gene. Until now this assumption was based on similarities in their amino acid sequences, on their often overlapping biological and immunological properties, and on nucleic acid sequence data for two members of the set (GH and CS). In the current study, we report the amplification in bacteria and the sequence analysis of DNA complementary to rat Prl mRNA. Two independent clones were obtained, one of which contained 823 bases including the entire sequence coding for rat prolactin and its signal peptide and parts of the 5‘- and 3”untranslated regions of the mRNA. The nucleotide sequences of the two cloned DNAs differ by three nucleotides. In addition, both predicted amino acid sequences also differ by about 14% from the published amino acid sequence of the protein. Although technical problems cannot be excluded for each of these discrepancies, the data suggest a revised structure for the protein and the possible existence of distinct nonallelic Prl genes. The results of this study have allowed us to compare the nucleotide sequences of the structural genes coding for each of the hormones of the Prl set. The codons for rPrl mRNA do not show the marked preference for GMP and CMP in the third position observed in rGH, hGH, and hCS mRNAs. rGH and rPrl mRNAs show 39% nucleic acid homology in the coding portion, but little homology in the untranslated regions. This differs from the comparison between hGH and hCS where the same degree of homology (about 93%) was found in both the coding and noncoding regions. Ten per cent of the codons of rPrl and rGH are identical, and 26% differ by only one base. Of the latter, only 58% result in amino acid changes, which most often are conservative. These results strongly support the hypothesis that the Prl and GH genes derive from a common precursor. The data allow us to suggest a date for this gene duplication event at around 380 million years ago.