Gene structure and polymorphism of an invertebrate nitric oxide synthase gene

S. Luckhart, R. Rosenberg

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Nitric oxide synthases (NOSs) are ubiquitous in living organisms. However, little is known about the evolution of this large gene family. The first inducible NOS to be described from an invertebrate regulates malaria parasite (Plasmodium spp.) development in the mosquito Anopheles stephensi. This single copy gene shows the highest homology to the vertebrate neuronal isoforms, followed by decreasing homology to endothelial and inducible isoforms. The open reading frame of 1247 amino acids is encoded by 19 exons, which span ≃33 kilobases. More than 50% of the mosquito exons, distributed around the putative heme, calmodulin, and FAD/NADPH cofactor-binding domains, are conserved with those of the three human genes. Repetitive elements identified within the larger introns include a polymorphic dinucleotide repeat, two tandem repeats, and a putative miniature inverted repeat transposable element. Sequence analysis and primer extension indicate that the upstream promoter is 'TATA-less' with multiple transcription start sites within ≃250 base pairs of the initiation methionine. Transcription factor binding sites in the 5'-flanking sequence demonstrate a bipartite distribution of lipopolysaccharide- and inflammatory cytokine-responsive elements that is strikingly similar to that described for vertebrate inducible NOS gene promoters.

Original languageEnglish (US)
Pages (from-to)25-34
Number of pages10
JournalGene
Volume232
Issue number1
DOIs
StatePublished - May 17 1999
Externally publishedYes

Keywords

  • Anopheles
  • Insect immunity
  • Malaria
  • Mosquito

ASJC Scopus subject areas

  • Genetics

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