The recent SARS-CoV-2 pandemic has refocused attention to the betacoronaviruses, only eight years after the emergence of another zoonotic betacoronavirus, the Middle East respiratory syndrome coronavirus (MERS-CoV). While the wild source of SARS-CoV-2 may be disputed, for MERS-CoV, dromedaries are considered as source of zoonotic human infections. Testing 100 immune-response genes in 121 dromedaries from United Arab Emirates (UAE) for potential association with present MERS-CoV infection, we identified candidate genes with important functions in the adaptive, MHC-class I (HLA-A-24-like) and II (HLA-DPB1-like), and innate immune response (PTPN4, MAGOHB), and in cilia coating the respiratory tract (DNAH7). Some of these genes previously have been associated with viral replication in SARS-CoV-1/-2 in humans, others have an important role in the movement of bronchial cilia. These results suggest similar host genetic pathways associated with these betacoronaviruses, although further work is required to better understand the MERS-CoV disease dynamics in both dromedaries and humans.
- MeSH
- adaptivní imunita genetika MeSH
- bronchy cytologie fyziologie MeSH
- cilie fyziologie MeSH
- COVID-19 genetika imunologie virologie MeSH
- genetická predispozice k nemoci MeSH
- interakce mikroorganismu a hostitele genetika imunologie MeSH
- koronavirové infekce genetika imunologie přenos virologie MeSH
- koronavirus MERS imunologie izolace a purifikace patogenita MeSH
- lidé MeSH
- objevující se infekční nemoci genetika imunologie přenos virologie MeSH
- přirozená imunita genetika MeSH
- protilátky virové MeSH
- replikace viru genetika imunologie MeSH
- respirační sliznice cytologie fyziologie MeSH
- SARS-CoV-2 imunologie patogenita MeSH
- velbloudi genetika imunologie virologie MeSH
- zdroje nemoci virologie MeSH
- zoonózy genetika imunologie přenos virologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Spojené arabské emiráty MeSH
BACKGROUND: Immune-response (IR) genes have an important role in the defense against highly variable pathogens, and therefore, diversity in these genomic regions is essential for species' survival and adaptation. Although current genome assemblies from Old World camelids are very useful for investigating genome-wide diversity, demography and population structure, they have inconsistencies and gaps that limit analyses at local genomic scales. Improved and more accurate genome assemblies and annotations are needed to study complex genomic regions like adaptive and innate IR genes. RESULTS: In this work, we improved the genome assemblies of the three Old World camel species - domestic dromedary and Bactrian camel, and the two-humped wild camel - via different computational methods. The newly annotated dromedary genome assembly CamDro3 served as reference to scaffold the NCBI RefSeq genomes of domestic Bactrian and wild camels. These upgraded assemblies were then used to assess nucleotide diversity of IR genes within and between species, and to compare the diversity found in immune genes and the rest of the genes in the genome. We detected differences in the nucleotide diversity among the three Old World camelid species and between IR gene groups, i.e., innate versus adaptive. Among the three species, domestic Bactrian camels showed the highest mean nucleotide diversity. Among the functionally different IR gene groups, the highest mean nucleotide diversity was observed in the major histocompatibility complex. CONCLUSIONS: The new camel genome assemblies were greatly improved in terms of contiguity and increased size with fewer scaffolds, which is of general value for the scientific community. This allowed us to perform in-depth studies on genetic diversity in immunity-related regions of the genome. Our results suggest that differences of diversity across classes of genes appear compatible with a combined role of population history and differential exposures to pathogens, and consequent different selective pressures.
The genomic structure of the Major Histocompatibility Complex (MHC) region and variation in selected MHC class I related genes in Old World camels, Camelus bactrianus and Camelus dromedaries were studied. The overall genomic organization of the camel MHC region follows a general pattern observed in other mammalian species and individual MHC loci appear to be well conserved. Selected MHC class I genes B-67 and BL3-7 exhibited unexpectedly low variability, even when compared to other camel MHC class I related genes MR1 and MICA. Interspecific SNP and allele sharing are relatively common, and frequencies of heterozygotes are usually low. Such a low variation in a genomic region generally considered as one of the most polymorphic in vertebrate genomes is unusual. Evolutionary relationships between MHC class I related genes and their counterparts from other species seem to be rather complex. Often, they do not follow the general evolutionary history of the species concerned. Close evolutionary relationships of individual MHC class I loci between camels, humans and dogs were observed. Based on the results of this study and on our data on MHC class II genes, the extent and the pattern of polymorphism of the MHC region of Old World camelids differed from most mammalian groups studied so far. Camels thus seem to be an important model for our understanding of the role of genetic diversity in immune functions, especially in the context of unique features of their immunoglobulin and T-cell receptor genes.
- MeSH
- druhová specificita MeSH
- fylogeneze * MeSH
- histokompatibilita - antigeny třídy I * genetika imunologie MeSH
- jednonukleotidový polymorfismus * MeSH
- molekulární evoluce * MeSH
- velbloudi * genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
This study brings new information on major histocompatibility complex (MHC) class III sub-region genes in Old World camels and integrates current knowledge of the MHC region into a comprehensive overview for Old World camels. Out of the MHC class III genes characterized, TNFA and the LY6 gene family showed high levels of conservation, characteristic for MHC class III loci in general. For comparison, an MHC class II gene TAP1, not coding for antigen presenting molecules but functionally related to MHC antigen presenting functions was studied. TAP1 had many SNPs, even higher than the MHC class I and II genes encoding antigen presenting molecules. Based on this knowledge and using new camel genomic resources, we constructed an improved genomic map of the entire MHC region of Old World camels. The MHC class III sub-region shows a standard organization similar to that of pig or cattle. The overall genomic structure of the camel MHC is more similar to pig MHC than to cattle MHC. This conclusion is supported by differences in the organization of the MHC class II sub-region, absence of functional DY genes, different organization of MIC genes in the MHC class I sub-region, and generally closer evolutionary relationships of camel and porcine MHC gene sequences analyzed so far.
- MeSH
- antigeny Ly klasifikace genetika MeSH
- fylogeneze MeSH
- hlavní histokompatibilní komplex * MeSH
- jednonukleotidový polymorfismus MeSH
- prasata MeSH
- skot MeSH
- TNF-alfa klasifikace MeSH
- velbloudi genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- skot MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
