Duplicated immunoglobulin gamma 2a genes in wild mice

The Japanese wild mouse, Mus musculus molossinus, has duplicated immunoglobulin gamma 2a genes, whereas most of the laboratory-strain mice have single gamma 2a genes. This duplication provides a unique system in which molecular mechanisms of the evolutionary rearrangement of the immunoglobulin gene can be studied. For this purpose it is important to elucidate the organization of the immunoglobulin genes surrounding the duplicated gamma 2a genes. It is also interesting to assess the distribution of this haplotype among the wild mouse population. Partially overlapping chromosomal segments that encompass the gamma 2b, gamma 2a-1, gamma 2a-2, and epsilon genes were isolated from phage libraries containing DNA fragments from M. m, molossinus. The organization of this region has been elucidated as 5'-gamma 2b-(18 kb)-gamma 2a-1-(19 kb)-gamma 2a-2-(14 kb)-epsilon-3'. Both gamma 2a-1 and gamma 2a-2 genes have their own switch regions in the 5' flanking region. Two homology units of 13 kb, each containing the gamma 2a gene, were identified. The homology units alternate with repetitive sequences of low homology, making the location of the recombination site obscure. Seventeen of 31 Japanese and Chinese wild mice screened had duplicated gamma 2a genes, indicating a wide distribution of this genetic event in the Asian wild mouse population. Moreover, three alleles each of the gamma 2b and gamma 2a loci have been observed in this small sample population. An unequal crossing-over event between heterologous haplotypes is proposed to account for the duplication of the gamma 2a gene, and a candidate for one member of the pair was identified among wild mouse haplotypes. These results suggest that the immunoglobulin heavy-chain gene family of the Japanese and Chinese wild mouse subspecies has accumulated not only polymorphic divergence due to point mutations, but also dynamic rearrangements such as gene duplication, during its recent evolution since divergence of these subspecies from the European subspecies about one million years ago.