Characterization of germ-line genes of the VGAM3.8 VH gene family from BALB/c mice.

Five germ-line genes of the VGAM3.8 VH family in BALB/c mice have been isolated from genomic libraries and sequenced. The genes are functional and three are expressed in antibodies of different specificities. Overall nucleotide sequence homologies within the family are greater than 90%, whereas homologies with other VH families are less than 70%. Southern blot hybridization and sequencing indicate a minimum family size of six genes. Differences in the coding regions are mostly confined to CDR, where there is a high replacement/silent substitution ratio, indicative of positive selection for diversification associated with Ag binding. VHVGAM3.8 sequences are highly conserved, and polymorphism in the coding regions appears to be very limited. Evidence is presented that the family has evolved, and been homogenized, by recombinatorial events.