Geliebter, Jan and Zeff, Richard A. and Schulze, Dan H. and Pease, Larry R. and Weiss, Elisabeth H. and Mellor, Andrew L. and Flavell, Richard A. and Nathenson, Stanley G.
Interaction Between Kb and Q4 Gene Sequences Generates the Kbm6 Mutation.
In: Molecular Cell Biology, Vol. 6: pp. 645-652
Genetic interaction as a mechanism for the generation of mutations is suggested by recurrent, multiple
nucleotide substitutions that are identical to nucleotide sequences elsewhere in the genome. We have sequenced
the mutant K gene from the bm6 mouse, which is one of a series of eight closely related, yet independently
occuring mutants known collectively as the "bg series." Two changes from the Kb gene are found, positioned
15 nucleotides apart: an A-to-T change and a T-to-C change in the codons corresponding to amino acids 116
and 121, resulting in Tyr-to-Phe and Cys-to-Arg substitutions, respectively. Hybridization analysis with an
oligonucleotide specific for the altered Kbm6 sequence identifies one donor gene, Q4, located in the Qa region of
the H-2 complex. The two altered nucleotides that differentiate Kbm6 and Kb are present in Q4 in a region where
Kb and Q4 are otherwise identical for 95 nucleotides, delineating the maximum genetic transfer between the two
genes. Because the Kbm6 mutation arose in an homozygous mouse these data indicate that the Q4 gene contains
the only donor sequence and demonstrates that Q-region gene sequences can interact with the Kb gene to
generate variant K molecules.