EVOLUTION OF A HOMOPURINE-HOMOPYRIMIDINE PENTANUCLEOTIDE REPEAT SEQUENCE UPSTREAM OF THE HUMAN INDUCIBLE NITRIC-OXIDE SYNTHASE GENE

We have identified a highly polymorphic pentanucleotide repeat (CCTTT) n within the 5'-putative promoter region of the human inducible nitric oxide synthase gene (iNOS, NOS2). Using a pair of specific primers de rived from the human iNOS gene, we have also amplified this iNOS repea t in DNA from the following species: chimpanzee, gorilla, orangutan an d macaque. As is found in man, both chimpanzees and gorillas are polym orphic at this locus. In contrast, the locus is monomorphic in macaque s and orangutans. While the average number of repeats is similar in go rilla and man, there are considerably fewer repeats in chimpanzees. A comparison of the sequences flanking the (CCTTT)n repeats among these closely related species demonstrates the presence of long stretches of homopurine-homopyrimidine residues. Similar polypurine/polypyrimidine stretches have been identified in the promoter regions of a number of other vertebrate genes where they have been associated with transcrip tional regulation, although a role for the (CCTTT)n repeat array in th e human iNOS gene has not yet been demonstrated. (C) 1997 Elsevier Sci ence B.V.