Abstract
The human major histocompatibility complex (MHC) region encodes three types of class II molecules designated HLA-DR, -DQ, and -DP. Both the HLA-DQ and -DP gene region comprise a duplicated tandem of A and B genes, whereas in macaques, only one set of genes is present per region. A substantial sequencing project on the DQ and DP genes in various macaque populations resulted in the detection of previously 304 unreported full-length alleles. Phylogenetic studies showed that humans and macaques share trans-species lineages for the DQA1 and DQB1 genes, whereas the DPA1 and DPB1 lineages in macaques appear to be species-specific. Amino acid variability plot analyses revealed that each of the four genes displays more allelic variation in macaques than is encountered in humans. Moreover, the numbers of different amino acids at certain positions in the encoded proteins are higher than in humans. This phenomenon is remarkably prominent at the contact positions of the peptide-binding sites of the deduced macaque DPβ-chains. These differences in the MHC class II DP regions of macaques and humans suggest separate evolutionary mechanisms in the generation of diversity.
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Acknowledgments
The authors wish to thank Francisca van Hassel for preparing the figures and Donna Devine for editing this article.
This work was supported by the National Institute of Health projects (NIH/NIAID HHSN272201100013C).
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Suppl. Table 1
(PDF 221 kb)
Suppl. Figure 1
Maximum Parsimony analysis of HLA-DQA1 and Mafa-DQA1 sequences. The evolutionary history was inferred using the Maximum Parsimony method. The most parsimonious tree with length = 618 is shown. The consistency index is (0.478011), the retention index is (0.803879), and the composite index is 0.448768 (0.384264) for all sites and parsimony-informative sites. The percentages of replicate trees in which the associated taxa clustered together in the bootstrap test (500 replicates) are shown next to the branches. The tree is drawn to scale, with branch lengths calculated using the average pathway method and are in the units of the number of changes over the whole sequence. The human sequences are depicted in green: bovine sequences, used as an out-group, are depicted in blue. (PDF 181 kb)
Suppl. Figure 2
Maximum Parsimony analysis of HLA-DPA1 and Mafa-DPA1 sequences. The evolutionary history was inferred using the Maximum Parsimony method. The most parsimonious tree with length = 387 is shown. The consistency index is (0.416667), the retention index is (0.752525), and the composite index is 0.371401 (0.313552) for all sites and parsimony-informative sites. The percentages of replicate trees in which the associated taxa clustered together in the bootstrap test (500 replicates) are shown next to the branches. The tree is drawn to scale, with branch lengths calculated using the average pathway method and are in the units of the number of changes over the whole sequence. The HLA-DPA1 sequences are depicted in green. Non-primate full-length DPA1 sequences, to use as an out-group, were not available. (PDF 133 kb)
Suppl. Figure 3
The DPA1-DPB1 pairs in the macaque cohorts. The pairs are sorted on the DPA1 lineages. Only those pairs are listed that were observed in at least two animals. The pairs A-F are identical sets of alleles in different macaques species. Abbreviations. Indo B: Indonesian cynomolgus macaques held at the BPRC. Indo A: Indonesian cynomolgus macaques held at AlphaGenesis inc. Ca/Vi: Cynomolgus macaques of Cambodian and/or Vietnamese origin. India B: Indian rhesus macaques held at the BPRC. India O: Indian rhesus macaques held at the ONPRC. Chin: Rhesus macaques of Chinese origin. Sang: Pigtailed macaques analyzed by Sanger sequencing. NGS: Pigtailed macaques analyzed by NG sequencing. (PDF 233 kb)
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Otting, N., van der Wiel, M.K.H., de Groot, N. et al. The orthologs of HLA-DQ and -DP genes display abundant levels of variability in macaque species. Immunogenetics 69, 87–99 (2017). https://doi.org/10.1007/s00251-016-0954-6
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DOI: https://doi.org/10.1007/s00251-016-0954-6