A statistical examination of hypervariability in complementarity-determining regions of immunoglobulins.

To determine the relative importance of gene conversion followed by natural selection and of natural selection for point mutation in generating variability in immunoglobulins, the numbers of synonymous and nonsynonymous substitutions in immunoglobulin sequences of various subgroups were estimated for complementarity-determining regions (CDRs) and for framework regions (FRs). Both the number of synonymous substitutions and the number of nonsynonymous substitutions in the CDR were found to exceed the corresponding numbers in the FR. Therefore, gene conversion is likely to be an important mechanism for providing variability in the CDR of immunoglobulins. The correlation coefficients between the number of synonymous substitutions and the number of nonsynonymous substitutions and between the substitution number in the CDR and that in the FR were found to be very low. Again, gene conversion is thought to be responsible for this finding.