Mechanisms for Evolutionary Divergence within the Prolactin Gene Family

Abstract

Transcriptional control of the expression of eukaryotic genes encoding proteins appears to be regulated both by DNA structures far removed from the gene (Klar et al., 1981; Nasmyth et al., 1981) and by signals found immediately upstream from the start of transcription (Breathnach and Chambon, 1981). The differential expression of members within a family of genes could therefore be dependent on structural differences adjacent to those genes. The exact location and nature of several of these adjacent regulatory regions have been examined in detail. The TATAA homology that occurs 20–30 base pairs (bp) 5′ to the start of transcription appears to specify the nucleotide at which RNA synthesis begins (Corden et al., 1980). A second set of sequences that are necessary for transcriptional efficiency is located upstream from the TATAA homology. The exact site of these modulating regions has recently been determined for the thymidine kinase gene of herpes simplex virus (McKnight and Kingsbury, 1982). In this gene, mutations in a guanine-rich segment between bases −7 and −61 and a cytosine-rich segment between bases −80 and −105 markedly decrease the efficiency of transcription. Although the −61 to −80 region of this gene contains the “CAAT” homology (Benoist et al., 1980; Efstratiadis et al., 1980; Liebhaber et al., 1980) found in a wide variety of genes, it does not appear to affect the level of thymidine kinase gene transcription. Steroid hormones induce transcription in a number of genes. DNA sequences necessary for this induction have been shown to be linked to the 5′ flanking region of such glucocorticoid-induced genes (Hynes et al., 1981; Lee et al., 1981; Robins et al., 1982). Further information on specific regulatory structures within other protein-coding genes may be obtained by comparison of the structure of genes within a family that are expressed differentially in response to different signals.