A molecular genetic approach to understanding the evolution of immunoglobulin gene structure and diversity

Abstract

Immune function in higher vertebrates is mediated primarily by multimeric glycoproteins found in the serum and on the surfaces of lymphoid cells. These molecules possess common structural features suggesting that they belong to a supergene family which may have originated from a common ancestral gene. Some multigenic members of the supergene family undergo unique forms of chromosomal rearrangement during somatic development. We have identified immunoglobulin heavy chainvariable region (VH) homologs in species representing critical points in the vertebrate radiation, examined their nucleotide sequences and found high degrees of organizational homology as well as localized regions of extended nucleotide (and amino acid) sequence identity with mammalian VH genes. The unexpected high degree of nucleotide sequence identity suggests that within this multigene family, selection may be operating at both the DNA and polypeptide levels.Using several different approaches, the VH gene families in lower vertebrates have been shown to be remarkably complex, discounting the possibility that a reduced number of germline genes accounts for the apparently restricted natureof lower vertebrate immune responses. The lower vertebrate germline VH genes possess prototypic recombination signal sequences, implicated in the somatic reorganization of mammalian immunoglobulin variable region genes, and segmentalreorganization resembling that seen in mammals has been observed in an elasmobranch. The detection of a recombination element flanked by short, direct repeats within the intervening sequence of one reptilian VH gene suggests that these sequences may be mobile, perhaps functioning outside of the immunoglobulin loci in other developmental processes. The complex nature of the variable region gene families and their capacity to undergo structural change during somatic development suggest that unique genetic mechanisms may govern their evolutionary stabilization and diversification. © 1985 by the American Society of Zoologists.