Project description: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.
Project description:The major histocompatibility complex (MHC) enables vertebrates to cope with pathogens and maintain healthy populations, thus making it a unique set of loci for addressing ecology and evolutionary biology questions. The aim of our study was to examine the variability of Heermann's Gull MHC class II (MHCIIB) and compare these loci with other Charadriiformes. Fifty-nine MHCIIB haplotypes were recovered from sixty-eight Heermann's Gulls by cloning, of them, twelve were identified as putative true alleles, forty-five as unique alleles, and two as pseudogenes. Intra and interspecific relationships indicated at least two loci in Heermann's Gull MHCIIB and trans-species polymorphism among Charadriiformes (coinciding with the documented evidence of two ancient avian MHCIIB lineages, except in the Charadriidae family). Additionally, sites under diversifying selection revealed a better match with peptide-binding sites inferred in birds than those described in humans. Despite the negative anthropogenic activity reported on Isla Rasa, Heermann's Gull showed MHCIIB variability consistent with population expansion, possibly due to a sudden growth following conservation efforts. Duplication must play an essential role in shaping Charadriiformes MHCIIB variability, buffering selective pressures through balancing selection. These findings suggest that MHC copy number and protected islands can contribute to seabird conservation.
Project description:A distinguishing characteristic of genes that code for the major histocompatibility complex (MHC) is that alleles often share more similarity between, rather than within species. There are two likely mechanisms that can explain this pattern: convergent evolution and trans-species polymorphism (TSP), in which ancient allelic lineages are maintained by balancing selection and retained by descendant species. Distinguishing between these two mechanisms has major implications in how we view adaptation of immune genes. In this study we analyzed exon 2 of the MHC class IIB in three passerine bird species in the genus Corvus: jungle crows (Corvus macrorhynchos japonensis) American crows (C. brachyrhynchos) and carrion crows (C. corone orientalis). Carrion crows and American crows are recently diverged, but allopatric, sister species, whereas carrion crows and jungle crows are more distantly related but sympatric species, and possibly share pathogens linked to MHC IIB polymorphisms. These patterns of evolutionary divergence and current geographic ranges enabled us to test for trans-species polymorphism and convergent evolution of the MHC IIB in crows. Phylogenetic reconstructions of MHC IIB sequences revealed several well supported interspecific clusters containing all three species, and there was no biased clustering of variants among the sympatric carrion crows and jungle crows. The topologies of phylogenetic trees constructed from putatively selected sites were remarkably different than those constructed from putatively neutral sites. In addition, trees constructed using non-synonymous substitutions from a continuous fragment of exon 2 had more, and generally more inclusive, supported interspecific MHC IIB variant clusters than those constructed from the same fragment using synonymous substitutions. These phylogenetic patterns suggest that recombination, especially gene conversion, has partially erased the signal of allelic ancestry in these species. While clustering of positively selected amino acids by supertyping revealed a single supertype shared by only jungle and carrion crows, a pattern consistent with convergence, the overall phylogenetic patterns we observed suggest that TSP, rather than convergence, explains the interspecific allelic similarity of MHC IIB genes in these species of crows.
Project description:Highly polymorphic genes with central roles in lymphocyte mediated immune surveillance are grouped together in the major histocompatibility complex (MHC) in higher vertebrates. Generally, across vertebrate species the class II MHC DRA gene is highly conserved with only limited allelic variation. Here however, we provide evidence of trans-species polymorphism at the DRA locus in domestic sheep (Ovis aries). We describe variation at the Ovar-DRA locus that is far in excess of anything described in other vertebrate species. The divergent DRA allele (Ovar-DRA*0201) differs from the sheep reference sequences by 20 nucleotides, 12 of which appear non-synonymous. Furthermore, DRA*0201 is paired with an equally divergent DRB1 allele (Ovar-DRB1*0901), which is consistent with an independent evolutionary history for the DR sub-region within this MHC haplotype. No recombination was observed between the divergent DRA and B genes in a range of breeds and typical levels of MHC class II DR protein expression were detected at the surface of leukocyte populations obtained from animals homozygous for the DRA*0201, DRB1*0901 haplotype. Bayesian phylogenetic analysis groups Ovar-DRA*0201 with DRA sequences derived from species within the Oryx and Alcelaphus genera rather than clustering with other ovine and caprine DRA alleles. Tests for Darwinian selection identified 10 positively selected sites on the branch leading to Ovar-DRA*0201, three of which are predicted to be associated with the binding of peptide antigen. As the Ovis, Oryx and Alcelaphus genera have not shared a common ancestor for over 30 million years, the DRA*0201 and DRB1*0901 allelic pair is likely to be of ancient origin and present in the founding population from which all contemporary domestic sheep breeds are derived. The conservation of the integrity of this unusual DR allelic pair suggests some selective advantage which is likely to be associated with the presentation of pathogen antigen to T-cells and the induction of protective immunity.
Project description:Abstract Major Histocompatibility Complex (MHC) genes are one of the most polymorphic gene groups known in vertebrates. MHC genes also exhibit allelic variants that are shared among taxa, referred to as trans‐specific polymorphism (TSP). The role that selection plays in maintaining such high diversity within species, as well as TSP, is an ongoing discussion in biology. In this study, we used deep‐sequencing techniques to characterize MHC class IIb gene diversity in three sympatric species of darters. We found at least 5 copies of the MHC gene in darters, with 126 genetic variants encoding 122 unique amino acid sequences. We identified four supertypes based on the binding properties of proteins encoded by the sequences. Although each species had a unique pool of variants, many variants were shared between species pairs and across all three species. Phylogenetic analysis showed that the variants did not group together monophyletically based on species identity or on supertype. An expanded phylogenetic analysis showed that some darter alleles grouped together with alleles from other percid fishes. Our findings show that TSP occurs in darters, which suggests that balancing selection is acting at the genotype level. Supertypes, however, are most likely evolving convergently, as evidenced by the fact that alleles do not form monophyletic groups based on supertype. Our research demonstrates that selection may be acting differently on MHC genes at the genotype and supertype levels, selecting for the maintenance of high genotypic diversity while driving the convergent evolution of similar MHC phenotypes across different species. In this study, we used deep‐sequencing techniques to characterize MHC class IIb gene diversity in three sympatric species of darters. We found at least 5 copies of the MHC gene in darters, with 126 genetic variants encoding 122 unique amino acid sequences, and we identified four supertypes based on the binding properties of proteins encoded by the sequences. Our findings show that trans‐specific polymorphism occurs in darters, which suggests that balancing selection is acting at the genotype level. Supertypes, however, are most likely evolving convergently, as evidenced by the fact that alleles do not form monophyletic groups based on supertype.
Project description:BackgroundThe New Zealand native frogs, family Leiopelmatidae, are among the most archaic in the world. Leiopelma hochstetteri (Hochstetter's frog) is a small, semi-aquatic frog with numerous, fragmented populations scattered across New Zealand's North Island. We characterized a major histocompatibility complex (MHC) class II B gene (DAB) in L. hochstetteri from a spleen transcriptome, and then compared its diversity to neutral microsatellite markers to assess the adaptive genetic diversity of five populations ("evolutionarily significant units", ESUs).ResultsL. hochstetteri possessed very high MHC diversity, with 74 DAB alleles characterized. Extremely high differentiation was observed at the DAB locus, with only two alleles shared between populations, a pattern that was not reflected in the microsatellites. Clustering analysis on putative peptide binding residues of the DAB alleles indicated four functional supertypes, all of which were represented in 4 of 5 populations, albeit at different frequencies. Otawa was an exception to these observations, with only two DAB alleles present.ConclusionsThis study of MHC diversity highlights extreme population differentiation at this functional locus. Supertype differentiation was high among populations, suggesting spatial and/or temporal variation in selection pressures. Low DAB diversity in Otawa may limit this population's adaptive potential to future pathogenic challenges.
Project description:The HLA-A locus represents a single copy gene that displays abundant allelic polymorphism in the human population, whereas, in contrast, a nonhuman primate species such as the rhesus macaque (Macaca mulatta) possesses multiple HLA-A-like (Mamu-A) genes, which parade varying degrees of polymorphism. The number and combination of transcribed Mamu-A genes present per chromosome display diversity in a population of Indian animals. At present, it is not clearly understood whether these different A region configurations are evolutionarily stable entities. To shed light on this issue, rhesus macaques from a Chinese population and a panel of cynomolgus monkeys (Macaca fascicularis) were screened for various A region-linked variations. Comparisons demonstrated that most A region configurations are old entities predating macaque speciation, whereas most allelic variation (>95%) is of more recent origin. The latter situation contrasts the observations of the major histocompatibility complex class II genes in rhesus and cynomolgus macaques, which share a high number of identical alleles (>30%) as defined by exon 2 sequencing.
Project description:Mitochondrial (mt) genomes of the sea urchins Strongylocentrotus intermedius and Mesocentrotus nudus demonstrate the identical patterns of intraspecific length variability of the ND6 gene, consisting of 489 bp (S variant) and 498 bp (L variant), respectively. For both species, the ND6 length difference is due to the 488A>G substitution, which changes the stop codon TAG in S variant for a tryptophan codon TGG in L variant and elongates the corresponding ND6 protein by three additional amino acids, Trp-Leu-Trp. The phylogenetic analysis based on mt genomes of sea urchins and related echinoderm groups from GenBank has shown the S and L ND6 variants as shared among the camarodont sea urchins; the rest of the echinoderms demonstrate the S variant only. The data suggest that the ND6 488A>G substitution can be the first example of the trans-species polymorphism in sea urchins, persisting at least since the time of the Odontophora diversification at the Eocene/Oligocene boundary (approximately 34 million years ago), which was characterized by an abrupt climate change and significant global ocean cooling. Alternative hypotheses, including the convergent RNA editing and/or codon reassignment, are not supported by direct comparisons of the ND6 gene sequences with the corresponding transcripts using the basic local alignment search tool (BLAST) of full sea urchin transcriptomes.
Project description:The ABO histo-blood group, the critical determinant of transfusion incompatibility, was the first genetic polymorphism discovered in humans. Remarkably, ABO antigens are also polymorphic in many other primates, with the same two amino acid changes responsible for A and B specificity in all species sequenced to date. Whether this recurrence of A and B antigens is the result of an ancient polymorphism maintained across species or due to numerous, more recent instances of convergent evolution has been debated for decades, with a current consensus in support of convergent evolution. We show instead that genetic variation data in humans and gibbons as well as in Old World monkeys are inconsistent with a model of convergent evolution and support the hypothesis of an ancient, multiallelic polymorphism of which some alleles are shared by descent among species. These results demonstrate that the A and B blood groups result from a trans-species polymorphism among distantly related species and has remained under balancing selection for tens of millions of years-to date, the only such example in hominoids and Old World monkeys outside of the major histocompatibility complex.
Project description:Major histocompatibility complex (Mhc) genes are believed to play a key role in the genetic basis of disease control. Although numerous studies have sought links between Mhc and disease prevalence, many have ignored the ecological and epidemiological aspects of the host-parasite interaction. Consequently, interpreting associations between prevalence and Mhc has been difficult, whereas discriminating alleles for qualitative resistance, quantitative resistance and susceptibility remains challenging. Moreover, most studies to date have quantified associations between genotypes and disease status, overlooking the complex relationship between genotype and the properties of the Mhc molecule that interacts with parasites. Here, we address these problems and demonstrate avian malaria (Plasmodium) parasite species-specific associations with functional properties of Mhc molecules (Mhc supertypes) in a wild great tit (Parus major) population. We further show that correctly interpreting these associations depends crucially on understanding the spatial variation in risk of infection and the fitness effects of infection. We report that a single Mhc supertype confers qualitative resistance to Plasmodium relictum, whereas a different Mhc supertype confers quantitative resistance to Plasmodium circumflexum infections. Furthermore, we demonstrate common functional properties of Plasmodium-resistance alleles in passerine birds, suggesting this is a model system for parasite-Mhc associations in the wild.