Evolution of immunoglobulin heavy chain variable region genes: a VH family can last for 150?200 million years or longer

Abstract

Many immunoglobulin variable region (IgV) genes are present in the vertebrate genome and provide a basis for antibody diversity. IgV genes have been classified into distinct families according to DNA sequence similarity. Comparisons of VH and VL genes from two mammalian species (mouse and human) have led to the conclusion that some V gene families are stable over 65 million years of evolution. Here we show that a VH family can be stable for 150-200 million years or longer. This conclusion is drawn from our extensive comparison of VH genes between two species of low vertebrates (rainbow trout and catfish), and from the estimation of species divergence time by the substitution rate of an IgM constant domain. The estimated speed of VH gene evolution explains the moderate degree of sequence similarity in VH gene families between a mammal (mouse) and a teleost (rainbow trout). The distribution of species-specific amino acid residues in certain VH families indicates that the process of sequence homogenization plays a major role in shaping the V gene family.

Immunoglobulin in fish—genes, expression and structure

“…A family is defined as sequences sharing at least 80% nucleotide identity, so the presence of a few families in a species could indicate low variability of the VH-segments. In human there are seven families (Matsuda et al, 1993;van Dijk et al, 1993), in mouse 14 (Tutter et al, 1991;Tutter & Riblet, 1989), in rainbow trout at least nine (Andersson & Matsunaga, 1995;Roman & Charlemagne, 1994) and in channel catfish six (Gha#ari & Lobb, 1991;Ventura-Holman et al, 1994;Warr et al, 1991), indicating that the number and variability of the VH-segments is similar in teleost fish and mammals. Other teleosts have also been studied in this respect although less thoroughly.…”

“…In teleost fish there are two species studied for their repertoire of VH genes-the rainbow trout (Oncorhynchus mykiss) and the channel catfish (Ictalurus punctatus)-representing di#erent phylogenetic branches. These species have more than 100 VH genes as judged from Southern blot analysis (Andersson & Matsunaga, 1995;Gha#ari & Lobb, 1991;Roman & Charlemagne, 1994;Ventura-Holman et al, 1994;Warr et al, 1991). The VH genes within a species usually group into families of related sequences.…”

A Model B-Cell Superantigen and the Immunobiology of B Lymphocytes

“…From cross-species V H sequence comparisons, the human V H 3 family has been assigned to the clan V H III, which arose before the mammalian radiation and has persisted with great evolutionary stability for at least 150 to 200 million years (44,45). In fact, of the three V H clans, clan V H III genes have undergone the least diversification (42, 46), and this clan V H III FR1/FR3 surface is among the most highly conserved throughout Ig evolution (47).…”

Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved

“…51-53 for reviews on mechanism), including rRNA (54) and IgV (55,56) genes. Evidence also exists for the occurrence of gene conversion events among mammalian cardiac MyHC genes and among chicken skeletal MyHC genes (57,58).…”