Molecular organization and in vitro expression of murine class III genes

These experiments demonstrate that at least two types of gene duplications have occurred during the evolution of the S region. The first type, which produced the C2 and factor B genes, involved a short segment of the chromosome encompassing a single gene. The related products have subsequently diverged yielding sequences which do not cross-hybridize. Further duplication of these genes has not been observed. The second type of duplication consisted of a much longer primordial sequence, spanning approximately 55 kb of genomic DNA and including at least two genes, C4/Slp and 21-hydroxylase. The duplicated sequences are separated by a segment of single copy sequence of as yet undefined length. These duplicated sequences have been relatively conserved. There is evidence that further duplication of this region is possible (as seen in the H-2w7 strain) although the exact nature of the increase in gene number has not been fully characterized. Detailed analysis of cosmid clones which span these two duplications has permitted the assignment of a new pair of loci to the S region, encoding 21-hydroxylase A and B. The advantage conferred by linkage of the gene encoding this adrenal steroid biosynthesis enzyme to the genes encoding complement components C2, factor B, and C4 is unclear, as is the advantage of the association of all of the class III genes with the remainder of the MHC. The availability of cloned sequences containing all of the class III genes permits further study of the factors which govern the tissue specificity of their expression and which confer androgen responsiveness on certain of the Slp alleles.