Substitution patterns in alleles of immunoglobulin V genes in humans and mice

Immunoglobulins (Igs) constitute a subfamily of rapidly evolving proteins. It is postulated that this characteristic is due mainly to the participation of these proteins in highly diverse functions of recognition and defense. Although this vision of rapid evolution in Igs is widely accepted, various studies have demonstrated that diverse and contradictory forces not yet completely understood converge in the evolution of these receptors. In a recent study of the substitution patterns in the alleles that form the human IGHV locus, we found that the variation in genetic and structural information does not occur homogeneously among the different genes, nor among the regions and positions conforming said locus. In view of these results and of the importance of a better understanding of the basic evolutionary process in specific receptors (such as Igs) for both immunology and molecular evolution, it is important to explore the nature of the diversification process in these proteins in detail. In this work, therefore, we analyzed the substitution patterns in all the alleles reported for loci IGKV and IGLV in humans and mice, and we compared the results with those previously observed in the human IGHV locus. We found that the process of evolutionary variation of the Igs reflect the diversity of selective pressures operating on the different loci, genes, sub-regions and positions; for example, diversification through substitution is generally centered on CDRs, but only few positions inside the CDRs were frequently substituted. In spite of this general tendency, it is possible to observe differences in the degree of diversification among loci, families and genes. These tendencies to modify only certain attributes of IGV genes seem to be in agreement with differential strategies associated with the restrictions of the molecular immune recognition mechanism. The complexity of the evolutionary patterns observed in this study leads us to think that the predispositions observed herein may also be due in part to processes of DNA dynamics.