HISTOCOMPATIBILITY GENE MUTATION-RATES IN THE MOUSE - A 25-YEAR REVIEW

Mutation rates of H2 and non-H2 histocompatibility genes in the mouse are examined over a 25-year period. Detected by skin graft rejections, the mutations were screened in inbred and hybrid mice from a continuo usly maintained and monitored colony and from a regularly supplied set of mice provided from the National Cancer Institute for monitoring of genetic integrity. Twenty-five H2 mutations were recovered, involving the K, D, L, and Ab loci, as well as over 80 mutations of non-H2 hist ocompatibility genes. Aside from a single allele at a single locus (H2 -K-b), the spontaneous mutation rate of H2 class I genes appears to be equivalent to that found estimated for non-H2 histocompatibility gene s, and comparable to rates reported for a variety of mouse genes. This is in contrast with previous suggestions that H2 genes mutate at orde rs of magnitude greater than do ''average'' mammalian genes. The discr epancy is attributed to the H2-K-b gene which accounts for over half o f all reported H2 mutations and which mutates spontaneously at a rate of 12 x 10(-4) per gene per generation. Furthermore, over half of the spontaneous H2-K-b mutations result in a single mutant phenotype (the ''bg'' group) which involve similar changes at amino acid residues 116 and 121. Thus, the high spontaneous mutation rate for H2-K-b appears to be the exception among major histocompatibility genes, rather than the rule.