Structure of Miniature Swine Class II DRB Genes: Conservation of Hypervariable Amino Acid Residues Between Distantly Related Mammalian Species

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 24; pp. 9798 - 9802
• Main Authors: Gustafsson, Kenth, Germana, Sharon, Hirsch, Francois, Pratt, karen, LeGuern, Christian
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.12.1990; National Acad Sciences
• Subjects: Alleles; Amino Acid Sequence; Amino acids; Animals; Antigens; Base Sequence; Biological and medical sciences; Biological Evolution; Cloning, Molecular; Complementary DNA; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Library; Genes, MHC Class II; Haplotypes; Histocompatibility antigens (hla, h-2 and other systems); HLA antigens; HLA-DR Antigens - genetics; Humans; MHC class II genes; Molecular immunology; Molecular Sequence Data; Nucleotides; Sequence Homology, Nucleic Acid; Spleen - immunology; Swine; Swine - immunology; Swine, Miniature - immunology; Transplantation; Human; Allele; Immunogenetics; Complementary DNA; Gene; Nucleotide sequence; Animal; Major histocompatibility system; Class II histocompatibility antigen; Primary structure; Comparative study; Aminoacid sequence
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.24.9798

As part of our studies of the class II genes of miniature swine, we have isolated and characterized cDNA clones corresponding to DRB genes from two major histocompatibility complex homozygous strains. Comparison of the sequences of these clones to those of human DRB genes revealed a striking amino acid homology between the hypervariable residues of SLA-DRBcand the human DRB1-0101 allele. The percentage of differences in these residues between the pig DRBcallele and the human DRB1-0101 allele was significantly lower (29%) than that between the DRB1-0101 allele and all other human alleles (average, 66.2%). This similarity was not seen in a comparison of the number of silent substitutions, by which the swine DRBcand the human DRB-0101 differed. Since phenotypic selection operates at the level of protein products rather than nucleotide sequences, these data suggest the existence of selective mechanisms that have resulted in similar hypervariable regions in certain alleles even in these widely disparate species. Consistent with this hypothesis, an examination of available murine and bovine class II sequences revealed a homology in hypervariable residues between the human DRB1-1401 allele and the mouse Eβs allele as well as a cow DRB allele. Consideration of these data along with intraspecies allelic sequence comparisons suggests that at least some of the interspecies similarities have emerged as the result of convergent evolution, possibly as the result of a need to react to common pathogens.