CLOSE PHYSICAL LINKAGE OF THE GENES ENCODING THE PNR-2 PS2 PROTEIN AND HUMAN SPASMOLYTIC PROTEIN (HSP)/

Trefoil proteins contain a conserved domain of distinctive structure. Three human trefoil proteins have been described to date of which the human spasmolytic polypeptide (hSP) and pNR-2/pS2 proteins have a simi lar pattern of expression in normal tissues. The genes encoding these two proteins were isolated from a human DNA library. Preliminary exper iments suggested that some recombinants contained both genes. Southern hybridisation showed that all the recombinants were derived from a si ngle stretch of DNA spanning 45 kb and suggested that the hSP gene was located downstream of the pNR-2/pS2 gene. Further experiments demonst rated that the two genes are transcribed in the same direction and tha t the distance between the 3' end of the pNR-2/pS2 gene and the 5' end of the hSP gene is 12.5 kb. The close linkage of these two genes is e vidence that they have evolved by gene duplication and that their simi lar pattern of expression in normal tissues could result from the rete ntion of common regulatory elements.