Allelic forms of rat κ chain genes: Evidence for strong selection at the level of nucleotide sequence

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Abstract
The genes that code for 2 allotypic forms of the rat .kappa. L chain constant region (C.kappa.) were cloned and the nucleotide sequence of 1172 base pairs of coding and flanking sequence was determined for both alleles. These sequences were compared to each other and to the corresponding sequences found in the mouse and human. Comparison of the LEW allele with mouse C.kappa. reveals 2 surprising features. There is an unusually large number of amino acid substitutions (21) relative to the total number of nucleotide changes (37) in the coding region. Comparison among several other mammalian genes reveals a larger proportion of silent changes. The rate of accumulation of base substitutions is the same within the coding region as it is in some 870 base pairs of noncoding sequence (including 3'' untranslated, 3'' flanking and 5'' intervening sequences). Comparison of the 2 allelic forms of rat C.kappa. shows the same unusual features in more extreme form. Base substitutions (12) in the coding region determine 11 amino acid differences.sbd.only 1 silent change exists. There are 12 base substitutions in the 318 base pairs of coding sequence (3.7% difference) and only 9 in the remaining 854 base pairs of noncoding DNA (1.1%), a highly significant difference. This degree of conservation of noncoding sequences and of silent sites within the coding region is unique among the mammalian genes studied thus far. There was probably strong selection for conservation of nucleotide sequences, both inside and outside the coding region, independent of the selection required to maintain the function and characteristic structure of the Ig domain itself. The functions of the nucleotide sequences that account for this selective pressure are unclear at the present time.