Individual exons encode the integral membrane domains of human myelin proteolipid protein

The gene encoding human proteolipid protein (PLP) was isolated from a human genomic library by hybridization with labeled DNA of a PLP-specific cDNA clone. The entire PLP gene spans approximately 17 kilobases. Restriction and sequence analysis revealed seven exons and six introns. The entire nucleotide sequences of the exons and of the exon-intron transitions were determined, and the intron lengths were measured. Exon I includes only ATGG of the translated region, the N-terminal methionine codon and G of glycine, the first amino acid of mature PLP. Each hydrophobic trans- and cis-membrane domain of PLP together with its adjacent hydrophilic sequence correlates closely with one exon of the gene except for the C-terminal transmembrane helix that is encoded by two exons. The amino acid sequence of human PLP derived from the nucleic acid sequence is highly conserved. Human and rat PLP are completely homologous, whereas only four amino acid residues are exchanged in bovine PLP sequence derived from protein sequencing and a partial cDNA clone. Homology search on the nucleic acid level among human, bovine, and rat brain PLPs indicates an unusually high homology in the coding regions. Hybridization analysis with DNA of human-rodent hybrid clones revealed that the gene encoding PLP segregates with human X chromosome in the region q13-q22.