Evolution of mouse immunoglobulin lambda genes.

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Abstract
The mouse has 4 C.lambda. and 2 V.lambda. genes. Charon 4A clones were isolated that contain all 6 .lambda. genes from a BALB/c germ-line library. The DNA sequences of the C.lambda.2, C.lambda.3 and C.lambda.4 genes are presented and what are apparently errors in previous reports of C.lambda.1 protein and DNA sequences are corrected. Cloned DNA were analyzed by restriction mapping and EM to determine the relationships among the various .lambda. genes. By heteroduplex analysis, 2 gene clusters containing JC.lambda.3-JC.lambda.1 and JC.lambda.2-JC.lambda.4 show homology extending from the J regions 5'' of C.lambda.3/C.lambda.2 to just 3'' of C.lambda.1/C.lambda.4. Other than the region between the genes, very little homology exists in the C.lambda. flanking regions. V.lambda.1 and V.lambda.2 genes show considerable homology extending into the 5'' flanking regions. Large inverted repeats are found in the 5'' flanking regions of V.lambda.1 and C.lambda.3, as well as in the 3'' flanking regions of both C.lambda. gene clusters. DNA sequence divergences between the C.lambda. genes indicate that an ancestral JC.lambda.x-JC.lambda.y gene cluster arose at about the time of the first mammals by duplication of a primordial JC.lambda. gene. The JC.lambda.x-JC.lambda.y gene cluster duplicated after the speciation of mouse and man and subsequently diverged into the present day JC.lambda.3-JC.lambda.1 and JC.lambda.2-JC.lambda.4 gene clusters. C.lambda.4, a pseudogene, became inactive at about the time of duplication of the ancestral JC.lambda.x-JC.lambda.y cluster. Comparison of DNA sequence divergence between the V.lambda.1 and V.lambda.2 genes demonstrates an anomaly. The percentage of amino acid replacement changes is approximately the same for V.lambda.1/V.lambda.2 as for C.lambda.3/C.lambda.2, implying that the ancestral V.lambda. gene was duplicated at the same time, and possibly together with, the JC.lambda.x-JC.lambda.y cluster. There are fewer silent changes than amino acid replacement changes between the V.lambda.1/V.lambda.2 genes, suggesting either that a selective pressure acted on the silent sites or that V.lambda. genes have only recently been duplicated. The possibility of a gene conversion event subsequent to a more ancient duplication is considered.