Nucleotide sequence of the human placental alkaline phosphatase gene. Evolution of the 5′ flanking region by deletion/substitution.

Abstract

Three closely related alkaline phosphatase (ALP) genes reside on the long arm of chromosome 2 in man. One of these genes (the placental ALP-1) encodes the classic heat-stable placental alkaline phosphatase. Another gene (the placental ALP-2) is closely related to the placental ALP-1 and may encode the so-called placental ALP-like enzyme of the testis and thymus. The third member of this gene family (the intestinal ALP gene) encodes the intestinal alkaline phosphatase. The expression of the placental ALP-1 and intestinal ALP genes is highly tissue-specific in spite of nearly 90% sequence similarity within their exons. To help determine the basis for this tissue specificity, the nucleotide sequence of the placental ALP-1 gene and some of its 5' flanking region has been determined and analyzed by comparison with placental ALP-2 and intestinal ALP gene sequences. The placental ALP-1 gene transcription unit has 4087 bases between the major cap site and the most distal of several reported 3' ends. The protein coding region is divided by 10 short introns varying in size from 74 to 241 nucleotides. Three of these introns bisect regions of the gene that encode residues conserved between the active site of the Escherichia coli enzyme and the human placental ALP. This result suggests that the human alkaline phosphatase genes have evolved in an intron-independent fashion. A comparison of the placental ALP-1 5' flanking sequence (up to -540) with the analogous sequence of the intestinal ALP gene revealed several deletion/substitutions which could be important in determining the tissue-specific expression of these genes.