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.
A research team led by Prof. MA Runlin at College of Life Science of University of Chinese Academy of Sciences reported 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.
△Figure: The hypothesis of ancient chromosome inversion in the ancestor of Cetruminantia. Genomic organization in the MHC region of Artiodactyla was compared with their phylogenetic relationships, listed on the left. This phylogenetic tree was adapted from Chen et al.. The organization of the MHC region in Suidae and Camelidae was inferred from the chromosome level genome assembly of pig and camel from the NCBI Genome database. This ancient inversion in the MHC region of the other five Ruminantia families remained to be determined due to the lack of genome information or poor genome assemblies.
This work was published online in Frontiers in Immunology on February 25. PhD student LI Chaokun is the first author, Prof. MA Runlin is the corresponding author. This work was supported in part by grants from the Chinese Academy of Sciences and the National Natural Science Foundation of China. The funding bodies had no role in the design of the study, in the collection, analysis, and interpretation of data, or in the writing of the manuscript.
