Evolutionary genomics of immunoglobulin-encoding Loci in vertebrates

Abstract

Immunoglobulins (or antibodies) are an essential element of the jawed vertebrate adaptive immune response system. These molecules have evolved over the past 500 million years and generated highly specialized proteins that recognize an extraordinarily large number of diverse substances, collectively known as antigens. During vertebrate evolution the diversification of the immunoglobulin-encoding loci resulted in differences in the genomic organization, gene content, and ratio of functional genes and pseudogenes. The tinkering process in the immunoglobulin-encoding loci often gave rise to lineage-specific characteristics that were formed by selection to increase species adaptation and fitness. Immunoglobulin loci and their encoded antibodies have been shaped repeatedly by contrasting evolutionary forces, either to conserve the prototypic structure and mechanism of action or to generate alternative and diversified structures and modes of function. Moreover, evolution favored the development of multiple mechanisms of primary and secondary antibody diversification, which are used by different species to effectively generate an almost infinite collection of diverse antibody types. This review summarizes our current knowledge on the genomics and evolution of the immunoglobulin-encoding loci and their protein products in jawed vertebrates.

Keywords: Antibodies; cladistic markers; comparative genomics.; genomic organization; gnathostomes; microRNA.

Fig. (1)

Diagrammatic representation of cluster and translocon type of immunoglobulin genomic organization with reference to the IgH loci. Cartilaginous fishes have cluster type of organization including germline-joined genes, whereas higher vertebrates have translocon type of Ig organization. C = constant gene; J = joining gene; D = diversity gene; V = variable gene; and n=variable number of genes.

Fig. (2)

Genomic organization of immunoglobulin light chain loci in representative tetrapod species. Constant, joining and variable genes are represented by gray, dotted black, and solid black vertical lines, respectively. Long vertical lines indicate functional genes whereas short vertical lines indicate pseudogenes. Vertical lines above and below the horizontal lines indicate that the Ig genes are located on opposite strands. In the frog κ- and σ-encoding loci the variable genes are located in different scaffolds. For this reason, these two loci are represented by separate horizontal lines. The figure is not drawn to scale. See details in Das et al. 2008.

Fig. (3)

Top Panel: Genomic architecture of miRNA-650-bearing V_λ genes in the human Ig-λ locus. The numbers the diagram indicate the positions of miR-650-bearing V_λ genes. Short vertical lines indicate V_λ genes, whereas long vertical lines indicate either Ig-λ constant genes (solid line) or joining genes (dotted line). Lower Panel: Schematic diagram of the overlap of miR-650 gene and the leader exon of V_λ gene is shown in a representative miR-650-bearing V_λ gene. Numbers correspond to the position of miR-650 gene and the positions of octamer, TATA box, leader exon, V-exon, and recombination signal sequence (RSS).