NUCLEOTIDE-SEQUENCE ANALYSIS OF THE HUMAN SALIVARY PROTEIN GENES HIS1AND HIS2, AND EVOLUTION OF THE STATH HIS GENE FAMILY

Human histatins are a family of low-M(r), neutral to very basic, histi dine-rich salivary polypeptides. They probably function as part of the nonimmune host defense system in the oral cavity. A 39-kb region of D NA containing the HIS1 and HIS2 genes was isolated from two human geno mic phage libraries as a series of overlapping clones. The nucleotide sequences of the HIS1 gene and part of the HIS2(1) gene were determine d. The transcribed region of HIS1 spans 8.5 kb and contains six exons and five introns. The HIS1 and HIS2(1) genes exhibit 89% overall seque nce identity, with exon sequences exhibiting 95% identity. The two loc i probably arose by a gene duplication event approximately 15-30 Mya. The HIS1 sequence data were also compared with that of STATH. Human st atherin is a low-M(r) acidic phosphoprotein that acts as an inhibitor of precipitation of calcium phosphate salts in the oral cavity. The HI S] and STATH genes show nearly identical overall gene structures. The HIS1 and STATH loci exhibit 77%-81% sequence identity in intron DNA an d 80%-88% sequence identity in noncoding exons but only 38%-43% sequen ce identity in the protein-coding regions of exons 4 and 5. These unus ual data suggest that HIS], HIS2, and STATH belong to a single gene fa mily exhibiting accelerated evolution between the HIS and STATH coding sequences.