Fifty-million-year-old polymorphism at an immunoglobulin variable region gene locus in the rabbit evolutionary lineage.

The Ig heavy chain variable region (V(H)) genes encode the antigen-binding regions of antibodies. The rabbit genome contains more than 100 V(H) genes, but only one (V(H)1) is preferentially used in the VDJ gene rearrangement. Three highly divergent alleles occur at this V(H)1 locus in most rabbit populations. These three V(H) alleles are also present in snowshoe hare populations, indicating that the polymorphism of the V(H)1 alleles is trans-specific. Here we report the results of a phylogenetic analysis of rabbit Ig germ-line V(H) genes (alleles) together with V(H) genes from humans and mice. We have found that all rabbit V(H) genes belong to one mammalian V(H) group (group C), which also includes various human and mouse V(H) genes. Using the rate of nucleotide substitution obtained from human and mouse V(H) sequences, we have estimated that the V(H)1 polymorphism in the rabbit lineage has been maintained for about 50 million years. This extremely long persistence of V(H)1 polymorphism is apparently caused by overdominant selection, though the real mechanism is unclear.

[1]  Kenneth M. Halanych,et al.  Multiple Substitutions Affect the Phylogenetic Utility of Cytochrome b and 12S rDNA Data: Examining a Rapid Radiation in Leporid (Lagomorpha) Evolution , 1999, Journal of Molecular Evolution.

[2]  R. Bontrop,et al.  The common marmoset: A new world primate species with limited Mhc class II variability , 1998 .

[3]  N. M. Brooke,et al.  A molecular timescale for vertebrate evolution , 1998, Nature.

[4]  M. Nei,et al.  Evolution by the birth-and-death process in multigene families of the vertebrate immune system. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[5]  K. Knight,et al.  B lymphocyte development in the rabbit. , 1997, International reviews of immunology.

[6]  W. van der Loo,et al.  The trans-species nature of rabbit b locus polymorphism is supported by studies on the snow-shoe hare , 1997, Immunogenetics.

[7]  D. Tilman,et al.  Biosphere 2 and Biodiversity--The Lessons So Far , 1996, Science.

[8]  C. Arthur,et al.  Compensatory aspects of allele diversity at immunoglobulin loci: gene correlations in rabbit populations devoid of light chain diversity (Oryctolagus cuniculus L.; Kerguelen Islands). , 1996, Genetics.

[9]  J. Archibald.  Fossil Evidence for a Late Cretaceous Origin of “Hoofed” Mammals , 1996, Science.

[10]  M. Kingzette,et al.  Evidence for limited B-lymphopoiesis in adult rabbits , 1996, The Journal of experimental medicine.

[11]  J. Klein,et al.  Mhc-DRB genes and the origin of New World monkeys. , 1995, Molecular phylogenetics and evolution.

[12]  E. Sasso,et al.  Ethnic differences of polymorphism of an immunoglobulin VH3 gene. , 1995, The Journal of clinical investigation.

[13]  A Rzhetsky,et al.  Phylogenetic test of the molecular clock and linearized trees. , 1995, Molecular biology and evolution.

[14]  L. Hood,et al.  Multiplex genotype determination at a DNA sequence polymorphism cluster in the human immunoglobulin heavy-chain region. , 1995, Genomics.

[15]  D. Watkins.  The evolution of major histocompatibility class I genes in primates. , 1995, Critical reviews in immunology.

[16]  M. Nei,et al.  Evolution of immunoglobulin VH pseudogenes in chickens. , 1995, Molecular biology and evolution.

[17]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[18]  M. Gouy,et al.  HOVERGEN: a database of homologous vertebrate genes. , 1994, Nucleic acids research.

[19]  J. Klein,et al.  The origin of the primate Mhc-DRB genes and allelic lineages as deduced from the study of prosimians. , 1994, Journal of immunology.

[20]  M. Nei,et al.  Divergent evolution and evolution by the birth-and-death process in the immunoglobulin VH gene family. , 1994, Molecular biology and evolution.

[21]  C. Raman,et al.  Preferential VH gene usage in rabbit Ig-secreting heterohybridomas. , 1994, Journal of immunology.

[22]  F. Tajima,et al.  Simple methods for testing the molecular evolutionary clock hypothesis. , 1993, Genetics.

[23]  J. Klein,et al.  Different modes of Mhc evolution in primates. , 1993, Molecular biology and evolution.

[24]  R. Kofler,et al.  Mouse Variable‐Region Gene Families: Complexity, Polymorphism and Use in non‐Autoimmune Responses , 1992, Immunological reviews.

[25]  M. Novacek,et al.  Mammalian phytogeny: shaking the tree , 1992, Nature.

[26]  K. Roux,et al.  Latent a1 VH germline genes in an a2a2 rabbit. Evidence for gene conversion at both the germline and somatic levels. , 1991, Journal of immunology.

[27]  R. Becker,et al.  Restricted utilization of germ-line VH genes in rabbits: implications for inheritance of VH allotypes and generation of antibody diversity. , 1991, Advances in experimental medicine and biology.

[28]  D. Metzger,et al.  Identification of rabbit genomic Ig-VH pseudogenes that could serve as donor sequences for latent allotype expression. , 1990, Journal of immunology.

[29]  R. Becker,et al.  Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes: Implications for the generation of antibody diversity , 1990, Cell.

[30]  M. Kasahara,et al.  Origin and function of Mhc polymorphism. , 1990, Chemical immunology.

[31]  L. Jin,et al.  Limitations of the evolutionary parsimony method of phylogenetic analysis. , 1990, Molecular biology and evolution.

[32]  J. Klein,et al.  Shared class II MHC polymorphisms between humans and chimpanzees. , 1989, Human immunology.

[33]  M. Nei,et al.  Positive darwinian selection observed at the variable-region genes of immunoglobulins. , 1989, Molecular biology and evolution.

[34]  L. Jin,et al.  Variances of the average numbers of nucleotide substitutions within and between populations. , 1989, Molecular biology and evolution.

[35]  M. Nei,et al.  Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[36]  Peter Parham,et al.  HLA-A and B polymorphisms predate the divergence of humans and chimpanzees , 1988, Nature.

[37]  M. Nei,et al.  Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection , 1988, Nature.

[38]  J. Klein,et al.  Nucleotide sequences of chimpanzee MHC class I alleles: evidence for trans‐species mode of evolution. , 1988, The EMBO journal.

[39]  J. Brostoff.  The Rabbit in Contemporary Immunological Research , 1988 .

[40]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[41]  M. Nei,et al.  Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. , 1986, Molecular biology and evolution.

[42]  J. Klein,et al.  Evolution of the major histocompatibility complex. , 1986, Critical reviews in immunology.

[43]  J. Gallarda,et al.  Organization of rabbit immunoglobulin genes. I. Structure and multiplicity of germ-line VH genes. , 1985, Journal of immunology.