CLONING OF THE HUMAN AND MURINE ROM1 GENES - GENOMIC ORGANIZATION AND SEQUENCE CONSERVATION

Rom-1 and peripherin are related membrane proteins of the photoreceptor outer segments. Both proteins are located at the rims of the photoreceptor disks, where they may act jointly in disk biogenesis. Mutations in the gene (RDS) encoding peripherin cause autosomal dominant retinitis pigmentosa, autosomal dominant punctata albescens and butterfly macular degeneration in man, and retinal degeneration slow in mice. To facilitate ROM1 mutation and linkage analysis in inherited retinal diseases, we cloned and characterized the human and murine ROM1 genes. In both species, the ROM1 coding region is contained within approximately 1.8 kb of genomic DNA and is interrupted by only two introns. The structures of the ROM1 and RDS genes are similar, with perfect conservation of the intron spike sites. Putative transcription regulatory regions of the ROM1 locus, 5' to an apparent transcription start site, were identified by cloning the mouse Rom-1 gene and comparing the sequence to the human homologue. Alignment of the human and murine rom-1 predicted protein sequences with the peripherin polypeptides of four species reveals a high degree of conservation (47% overall identity between the six proteins) in the central hydrophilic domain of the two family members. Despite this conservation of sequence, the predicted pI's of only this region of rom-1 and peripherin differ substantially, being 5.2 and 8.2, respectively. The charge difference in this region may mediate the non-covalent association of these two proteins in vivo. The conserved genomic structure and sequence of ROM1 and RDS indicates that these genes evolved from a common ancestor by a duplication event.