Gene conversion generates hypervariability at the variable regions of kallikreins and their inhibitors.

The two mechanisms for generating hypervariability at the reactive center of serine proteases and their inhibitors are gene conversion followed by natural selection and natural selection for point mutation. One way to clarify the effects of these two mechanisms is to calculate separately the number of nonsynonymous substitutions and that of synonymous substitutions at the variable regions and at the conserved regions. Our data analysis shows that not only the number of nonsynonymous substitutions but also the number of synonymous substitutions at the variable regions exceed the corresponding numbers at the conserved regions. Thus gene conversion has provided needed variability at the variable regions of serine proteases and their inhibitors. Natural selection has helped perpetuate such variability.