Factors important in evolutionary shaping of immunoglobulin gene loci.

BACKGROUND: The extraordinary diversity characterizing the antibody repertoire is generated by both evolution and lymphocyte development. Much of this diversity is due to the existence of immunoglobulin (Ig) variable region gene segment libraries, which were diversified during evolution and, in higher vertebrates, are used in generating the combinatorial diversity of antibody genes. The aim of the present study was to address the following questions: What evolutionary parameters affect the size and structure of gene libraries? Are the number of genes in libraries of contemporary species, and the corresponding gene locus structure, a random result of evolutionary history, or have these properties been optimized with respect to individual or population fitness? If a larger number of genes or different genome structures do not increase the fitness, then the current structure is probably optimized.

RESULTS: We used a simulation of variable region gene library evolution. We measured the effect of different parameters on gene library size and diversity, and the corresponding fitness. We found compensating relationships between parameters, which optimized Ig library size and diversity.

CONCLUSIONS: We conclude that contemporary species' Ig libraries have been optimized by evolution in terms of Ig sequence lengths, the number and diversity of Ig genes, and antibody-antigen affinities.