CHARACTERIZATION OF THE NOVEL GENE G11 LYING ADJACENT TO THE COMPLEMENT C4A GENE IN THE HUMAN MAJOR HISTOCOMPATIBILITY COMPLEX

Twelve transcriptional units have now been located in a 160 kb segment of DNA that includes the genes encoding members of the serum compleme nt system C2, Factor B (Bf) and C4 within the class III region of the human major histocompatibility complex (MHC). The common arrangement o f these genes is 1-C4A-(P450c21A-YA-XA]-C4B-[P450c21-B-YB]-TNX-cen. Ch aracterisation of cDNA and genomic clones corresponding to the novel g ene G11 has revealed that the gene spans similar to 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 transcriptio nal start site of the C4A gene. The similar to 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 pr oducts 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 polypeptides shar e homology with a limited number of proteins including human cytochrom e 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 seg ment of DNA flanking the C4B gene has revealed that 914 bp of the 3' e nd of the G11 gene also lies 611 bp from the transcriptional start sit e of the C4B gene. This suggests that the 3' end of the G11 gene was i nvolved in the original duplication event that gave rise to the two C4 /P450c21 loci. In addition this segment of DNA derived from the G11 ge ne would appear to form the 3' end of the YA transcriptional unit whic h lies between the C4A and C4B genes and which is expressed only in fe tal and adult adrenal glands.