Characterisation of the novel gene G11 lying adjacent to the complement C4A gene in the human major histocompatibility complex

Abstract

Twelve transcriptional units have now been located in a 160 kb segment of DNA that includes the genes encoding members of the serum complement system C2, Factor B (Bf) and C4 within the class III region of the human major histocompatibility complex (MHC). The common arrangement of these genes is tel-C2-Bf-RD-G11-C4A-(P450c21A-YA-XA)-C4B-(P450c21B-YB]-TNX-cen. Characterisation of cDNA and genomic clones corresponding to the novel gene G11 has revealed that the gene spans ∼9.1 kb of DNA and is split into 7 exons. The 5′ end of the gene Is associated with a CpG-island while the 3′ end of the gene lies 611 bp from the transcriptional start site of the C4A gene. The ∼1.4 kb G11 mRNA, which is expressed In a number of different cell types Including monocytes, hepatocytes, epithelial cells, T and B lymphocytes, encodes protein products of 254 or 258 amino acids due to differential use of two splice sites lying 12 bp apart at the end of exon 3. These polypeptldes share homology with a limited number of proteins including human cytochrome P450XIB1 and the tyrosine kinase transforming protein from fujinami virus. Duplication of the C4/P450c21 transcriptional unit occurred by a nonhomologous recombination event. Sequence analysis of a 1.5 kb segment of DNA flanking the C4B gene has revealed that 914 bp of the 3′ end of the G11 gene also lies 611 bp from the transcriptional start site of the C4B gene. This suggests that the 3′ end of the G11 gene was involved in the original duplication event that gave rise to the two C4/P450c21 loci. In addition this segment of DNA derived from the G11 gene would appear to form the 3′ end of the YA transcriptional unit which lies between the C4A and C4B genes and which is expressed only in fetal and adult adrenal glands.