Ruminants are critical as prey in transferring solar energy fixed by plants into carnivorous species, yet the genetic signature of the driving forces leading to the evolutionary success of the huge number of ruminant species remains largely unknown. Here we report a complete DNA map of the major histocompatibility complex (MHC) of the addax (Addax nasomaculatus) genome by sequencing a total of 47 overlapping BAC clones previously mapped to cover the MHC region. The addax MHC is composed of 3,224,151 nucleotides, harboring a total of 150 coding genes, 50 tRNA genes, and 14 non-coding RNA genes. The organization of addax MHC was found to be highly conserved to those of sheep and cattle, highlighted by a large piece of chromosome inversion that divided the MHC class II into IIa and IIb subregions. It is now highly possible that all of the ruminant species in the family of Bovidae carry the same chromosome inversion in the MHC region, inherited from a common ancestor of ruminants. Phylogenetic analysis indicated that DY, a ruminant-specific gene located at the boundary of the inversion and highly expressed in dendritic cells, was possibly evolved from DQ, with an estimated divergence time ~140 million years ago. Homology modeling showed that the overall predicted structure of addax DY was similar to that of HLA-DQ2. However, the pocket properties of P1, P4, P6, and P9, which were critical for antigen binding in the addax DY, showed certain distinctive features. Structural analysis suggested that the populations of peptide antigens presented by addax DY and HLA-DQ2 were quite diverse, which in theory could serve to promote microbial regulation in the rumen by ruminant species, contributing to enhanced grass utilization ability. In summary, the results of our study helped to enhance our understanding of the MHC evolution and provided additional supportive evidence to our previous hypothesis that an ancient chromosome inversion in the MHC region of the last common ancestor of ruminants may have contributed to the evolutionary success of current ruminants on our planet.

反刍动物作为将植物固定的太阳能转移到食肉物种中的猎物至关重要，但是导致大量反刍动物进化成功的驱动力的遗传特征仍然未知。在这里，我们报告了addax的主要组织相容性复合体（MHC）的完整DNA图（鼻Addax nasomaculatus通过对总共47个重叠的BAC克隆进行测序来对基因组进行测序，这些BAC克隆先前已被映射以覆盖MHC区。addax MHC由3,224,151个核苷酸组成，总共包含150个编码基因，50个tRNA基因和14个非编码RNA基因。发现Addax MHC的组织与绵羊和牛的组织高度保守，其突出之处是一大条染色体倒置，将II类MHC分为IIa和IIb子区域。现在，很有可能是牛科的所有反刍动物物种在MHC区域中都具有相同的染色体倒置，这是由反刍动物的共同祖先继承而来的。系统发育分析表明DY，位于反演边界并在树突状细胞中高表达的反刍动物特异性基因，可能是由 DQ，估计发散时间约为1.4亿年前。同源性建模表明，addax DY的总体预测结构与HLA-DQ2相似。但是，P1，P4，P6和P9的口袋性质对Addax DY中的抗原结合至关重要，它具有某些独特的特征。结构分析表明，addax DY和HLA-DQ2呈递的肽抗原种群非常多样，从理论上讲可以促进反刍动物对瘤胃中微生物的调控，从而提高草的利用能力。综上所述，