Searching for coding sequences in the mammalian genome: the H-2K region of the mouse MHC is replete with genes expressed in embryos.

We have searched for expressed genes in 170 kb of cosmid cloned DNA from the H-2K region of the mouse MHC. This region is known to contain two genes, H-2K and K2. We identified unique/low copy sequences evenly spaced along the cloned DNA, and used these as probes to search for conserved sequences in Southern blots from a variety of mammalian species. The majority of the unique sequences were found to have homologues and most of these were associated with CpG non-methylated islands. Northern blot analysis and isolation of clones from 5.5 and 10.5-day embryo cDNA libraries showed five additional genes encoded in the H-2K region. Four of these are abundant in embryos; the fifth is exclusively expressed in lymphoid cells. Our data indicate a minimum of seven genes in 170 kb, an unexpectedly high gene density. These results differ from two recent studies where similar lengths of cloned DNA were examined for expressed genes, and only one, or a part of one gene was found. The combined data suggest that the spatial organization of genes in the mammalian genome may not be random.