EVOLUTION OF THE STRUCTURAL REPERTOIRE OF THE HUMAN V-H AND V-KAPPA GERMLINE GENES

Variable genes of human Ig are classified in families and clans which reflect the early events of gene duplication in the evolution of the l ocus. This organization in multiple copies of variable genes plus the somatic processes of recombination and hypermutation allows the immune system to generate an antibody repertoire of great diversity, At pres ent the role that somatic processes play in the generation of that div ersity is understood with some detail. It is a matter of hard controve rsy, however, which selective pressures have shaped the evolution of t he germline genes of Ig and, consequently, what the role of this germl ine component in the generation of the antibody diversity actually is, Previous studies of our group have showed that the structural reperto ire of Ig - determined by the canonical structures - is an important f actor to determine the recognition properties of the antibodies. Compl ete knowledge of the sequences of the human V-H and V-kappa loci is av ailable to analyze the evolution of the structural repertoire of these loci. Two phylogenetic gene trees were built from the functional germ line genes and the evolution of the structural repertoire was studied, We report that for both loci the canonical structures are not randoml y distributed within the tree. Conversely, it is shown that the evolut ion of the structural repertoire follows a gradual process of diversif ication. This indicates a correlation between the evolution of genes a nd the structural repertoire, although important differences are found in the patterns of evolution of the structural repertoire between V-H and V-kappa. Based on those results we propose a primordial structura l repertoire for V-H and V-kappa. The general properties and an outlin e of the three-dimensional structure of this primordial repertoire are given.