Mouse immunoglobulin allotypes: post-duplication divergence of γ2a and γ2b chain genes

Abstract

Sequence analysis of the mouse immunoglobulin heavy chain constant-region gene family has provided interesting clues to its evolutionary history¹. There are eight genes, each consisting of four exons separated by noncoding sequences, which encode the three globular domains and the small hinge region of the constant-region polypeptide. The eight genes are believed to have arisen by duplications from a single ancestral gene and in particular, the γ2a and γ2b genes are thought to have been the result of a recent duplication^2–5. They show, however, a rather surprising pattern of sequence divergence^2–7. Schreier et al.⁷ have reported considerable sequence divergence between the two γ2a alleles carried by the BALB/c and C57BL/6 inbred mouse strains; at many of the sites at which the two alleles differ, the BALB/c allele is identical to the BALB/c γ2b gene. Thus it has been suggested that the BALB/c γ2a gene has been converted by the γ2b gene. We have now sequenced the C57BL/6 γ2b gene and report that the divergence between the two γ2b alleles is very much less than that between the γ2a alleles and is consistent with point mutations. However, it is also clear that the third domain (CH3) of the C57BL/6 γ2a gene has diverged so much from the homologous domain in the BALB/c γ2a gene and the two γ2b alleles that it may have derived from elsewhere in the heavy chain family and become inserted in the γ2a gene by a double unequal crossing-over event.