EVOLUTION OF THE MAJOR HISTOCOMPATIBILITY COMPLEX (MHC) IN MAMMAL: THE PIG SEQUENCE

¹ LREG, INRA CEA Jouy en Josas 78350 France

² Wellcome Trust Sanger Institute , Cambridge CB10 1SA UK

³ Tokai University of School Medicine, Isehara, Kanagawa, 259-1193 Japan

Whereas in mammalian species studied so far the MHC is on a single chromosomal segment, in pig the MHC is disrupted by the centromere with the class II region on the long arm of chromosome 7 and class III and class I regions on the short arm. The class II region in pig spreads over 410 kb from COL11A2 (telomeric end) to DRA (centromeric end) It contains fourteen actual class II genes and pseudo genes, including only one set of DM, DO, DQ, DR functional alpha and beta genes but no DP sequences. The six non-MHC related genes existing in HLA are found in orthologous position. The BTLNII gene which ended the class II region in human, is encoded in pig by the opposite strand of the centromeric end of the class III region. In HLA, the segment between class II and class III is composed of a long range of G+C% mosaic domains. This segment contains the centromere in pig. The 650 kb-long class III region which contains 56 genes from NOTCH4 to BAT1 genes, is highly conserved. Absence of duplicated C4-CYP21 locus is confirmed. The class I region is significantly shorter in pig compared to HLA. It spreads along 990 kb from the gene SLA-6 to the MOG gene. Only ten class I related sequences exist in pig and some of them are specific The sequence analysis revealed three class I duplication rounds between a frame of conserved segments and the existence of one ancestral MHC gene.