Nejvíce citovaný článek - PubMed ID 25165529
Contrasting patterns of polymorphism and selection in bacterial-sensing toll-like receptor 4 in two house mouse subspecies
The house mouse, Mus musculus, is a widely used animal model in biomedical research, with classical laboratory strains (CLS) being the most frequently employed. However, the limited genetic variability in CLS hinders their applicability in evolutionary studies. Wild-derived strains (WDS), on the other hand, provide a suitable resource for such investigations. This study quantifies genetic and phenotypic data of 101 WDS representing 5 species, 3 subspecies, and 8 natural Y consomic strains and compares them with CLS. Genetic variability was estimated using whole mtDNA sequences, the Prdm9 gene, and copy number variation at two sex chromosome-linked genes. WDS exhibit a large natural variation with up to 2173 polymorphic sites in mitogenomes, whereas CLS display 92 sites. Moreover, while CLS have two Prdm9 alleles, WDS harbour 46 different alleles. Although CLS resemble M. m. domesticus and M. m. musculus WDS, they differ from them in 10 and 14 out of 16 phenotypic traits, respectively. The results suggest that WDS can be a useful tool in evolutionary and biomedical studies with great potential for medical applications.
- MeSH
- alely MeSH
- divoká zvířata genetika MeSH
- druhová specificita MeSH
- fenotyp MeSH
- genetická variace * MeSH
- histonlysin-N-methyltransferasa genetika MeSH
- mitochondriální DNA genetika MeSH
- myši * genetika MeSH
- variabilita počtu kopií segmentů DNA MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši * genetika MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- histonlysin-N-methyltransferasa MeSH
- mitochondriální DNA MeSH
- prdm9 protein, mouse MeSH Prohlížeč
Immune genes show remarkable levels of adaptive variation shaped by pathogen-mediated selection. Compared to humans, however, population polymorphism in animals has been understudied. To provide an insight into immunogenetic diversity in birds, we sequenced complete protein-coding regions of all Toll-like receptor (TLR) genes with direct orthology between mammals and birds (TLR3, TLR4, TLR5 and TLR7) in 110 domestic chickens from 25 breeds and compared their variability with a corresponding human dataset. Chicken TLRs (chTLRs) exhibit on average nine-times higher nucleotide diversity than human TLRs (hTLRs). Increased potentially functional non-synonymous variability is found in chTLR ligand-binding ectodomains. While we identified seven sites in chTLRs under positive selection and found evidence for convergence between alleles, no selection or convergence was detected in hTLRs. Up to six-times more alleles were identified in fowl (70 chTLR4 alleles vs. 11 hTLR4 alleles). In chTLRs, high numbers of alleles are shared between the breeds and the allelic frequencies are more equal than in hTLRs. These differences may have an important impact on infectious disease resistance and host-parasite co-evolution. Though adaptation through high genetic variation is typical for acquired immunity (e.g. MHC), our results show striking levels of intraspecific polymorphism also in poultry innate immune receptors.
- MeSH
- frekvence genu MeSH
- genetická variace * MeSH
- kur domácí * MeSH
- lidé MeSH
- sekvenční analýza DNA MeSH
- toll-like receptory genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- toll-like receptory MeSH
Immunity exhibits extraordinarily high levels of variation. Evolution of the immune system in response to host-pathogen interactions in particular ecological contexts appears to be frequently associated with diversifying selection increasing the genetic variability. Many studies have documented that immunologically relevant polymorphism observed today may be tens of millions years old and may predate the emergence of present species. This pattern can be explained by the concept of trans-species polymorphism (TSP) predicting the maintenance and sharing of favourable functionally important alleles of immune-related genes between species due to ongoing balancing selection. Despite the generality of this concept explaining the long-lasting adaptive variation inherited from ancestors, current research in TSP has vastly focused only on major histocompatibility complex (MHC). In this review we summarise the evidence available on TSP in human and animal immune genes to reveal that TSP is not a MHC-specific evolutionary pattern. Further research should clearly pay more attention to the investigation of TSP in innate immune genes and especially pattern recognition receptors which are promising candidates for this type of evolution. More effort should also be made to distinguish TSP from convergent evolution and adaptive introgression. Identification of balanced TSP variants may represent an accurate approach in evolutionary medicine to recognise disease-resistance alleles.
- MeSH
- alely MeSH
- hlavní histokompatibilní komplex genetika imunologie MeSH
- interakce hostitele a patogenu genetika imunologie MeSH
- lidé MeSH
- molekulární evoluce MeSH
- polymorfismus genetický genetika imunologie MeSH
- přirozená imunita genetika imunologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH