Amino acid diversity of immunoglobulins as a product of molecular evolution

Based on population genetics theory of the evolution of multigene families, the sequence variability of the variable regions of immunoglobulins compiled by Kabat et al. (1976) has been analysed. An amino acid identity coefficient either within or between species is calculated separately for both the hypervariable and the framework regions. Under the somatic mutation hypothesis, the somatic component of amino acid diversity is in addition to the germ line component and should contribute an amount of change between the hypervariable and framework regions that is independent of the time since the divergence of any two immunoglobulin gene families. The relationship between the identity coefficient of the hypervariable region and that of the framework region is shown to be not in accord with such prediction. The result indicates that the rate of evolutionary accumulation of amino acid replacements in the hypervariable region is roughly three times more rapid than in the framework region and the hypervariability within a species is a necessary consequence of the high evolutionary rate.