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1.
Joëlle Goüy de Bellocq Franz Suchentrunk Stuart J. E. Baird Helmut Schaschl 《Immunogenetics》2009,61(2):131-144
We surveyed the genetic diversity of the expressed major histocompatibility complex class II DQA locus in natural populations
of European brown hares, Lepus europaeus, from Austria and Belgium (267 individuals in total). Based on cDNA sequences, we designed hare-specific primers to amplify
the highly variable second exon of the DQA gene. Using cloning–sequencing methodology and capillary electrophoresis single-strand
conformation polymorphism, we found ten alleles of the DQA exon 2 locus across these two European regions, of which eight
are described for the first time. To search for signals of selection and recombination in the evolution of the DQA gene within
the leporids, we augmented our sample with orthologous DQA alleles from the European rabbit, Oryctolagus cuniculus, in order to carry out a species level, species pairwise comparison. We found evidence of recombination in the history of
the DQA sequences in leporids with some recombinant alleles bridging the species divide. In both species, selection on peptide
binding site codons can be detected, though stronger for the rabbit. This result suggests that there may be a differential
selection pressure in the deeper evolutionary history of these two species due to differences in several demographic and ecological
traits likely subjecting them to differential selection by parasites. Finally, evolutionary relationships show a widespread
and statistically significant intermingling of alleles from the two species. The many macroparasites shared between hares
and rabbits may explain this pattern of trans-species polymorphism.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
The nucleotide sequence data reported in this paper have been submitted to Genbank and have been assigned the accession numbers
FJ225335–FJ225346. 相似文献
2.
The major histocompatibility complex (MHC) is an essential part of the vertebrate immune response. MHC genes may be classified as classical, non-classical or non-functional pseudogenes. We have investigated the diversity of class I MHC genes in the brushtail possum, a marsupial native to Australia and an introduced pest in New Zealand. The MHC of marsupials is poorly characterised compared to eutherian mammal species. Comparisons between marsupials and eutherians may enhance understanding of the evolution and functions of this important genetic region. We found a high level of diversity in possum class I MHC genes. Twenty novel sequences were identified using polymerase chain reaction (PCR) primers designed from existing marsupial class I MHC genes. Eleven of these sequences shared a high level of homology with the only previously identified possum MHC class I gene TrvuUB and appear to be alleles at a single locus. Another seven sequences are also similar to TrvuUB but have frame-shift mutations or stop codons early in their sequence, suggesting they are non-functional alleles of a pseudogene locus. The remaining sequences are highly divergent from other possum sequences and clusters with American marsupials in phylogenetic analysis, indicating they may have changed little since the separation of Australian and American marsupials. 相似文献
3.
High variability in the MHC class II DA beta chain of the brushtail possum (<Emphasis Type="Italic">Trichosurus vulpecula</Emphasis>) 总被引:1,自引:0,他引:1
The diversity of class II major histocompatibility complex (MHC) loci was investigated in the brushtail possum, an important
marsupial pest species in New Zealand. Immunocontraception, a form of fertility control that generates an autoimmune response,
is being developed as a population control method for the possum. Because the immune response is partly under genetic control,
an understanding of immunogenetics in possum will be crucial to the development of immunocontraceptive vaccines. MHC molecules
are critical in the vertebrate immune response. Class II MHC molecules bind and present exogenously derived peptides to T
lymphocytes and may be important in the presentation of immunocontraceptives. We used polymerase chain reaction primers designed
to amplify the peptide binding region of possum class II MHC genes to isolate sequences from 49 animals. We have previously
described 19 novel alleles from the DAB locus in the possum (Holland et al., Immunogenetics 60:449–460, 2008). Here, we report on another 11 novel alleles isolated from possum DAB, making this the most diverse marsupial locus described so far. This high level of diversity indicates that DAB is an important MHC locus in the possum and will need to be taken into account in the design of immunocontraceptive vaccines. 相似文献
4.
The major histocompatibility complex (MHC) is central to the vertebrate immune system and its highly polymorphic genes are considered to influence several life-history traits of individuals. To characterize the MHC in a natural population of blue tits (Cyanistes caeruleus) we investigated the class I exon 3 diversity of more than 900 individuals. We designed two pairs of motif-specific primers that reliably amplify independent subsets of MHC alleles. Applying denaturing gradient gel electrophoresis (DGGE) we obtained 48 independently inherited units of unique band patterns (DGGE-haplogroups), which were validated in a segregation analysis within 105 families. In a second approach, we extensively sequenced 6 unrelated individuals to confirm that DGGE-haplogroup composition reflects individual allelic variation. The highest number of different DGGE-haplogroups in a single individual corresponded in 19 MHC exon 3 sequences, suggesting a minimum of 10 amplified MHC class I loci in the blue tit. In total, we identified 50 unique functional and 3 non-functional sequences. Functional sequences showed high levels of recombination and strong positive selection in the antigen binding region, whereas nucleotide diversity was comparatively low in the range of all passerine species. Finally, in a phylogenetic comparison of passerine MHC class I exon 3 sequences we discuss conflicting evolutionary signals possibly due to recent gene duplication, recombination events and concerted evolution. Our results indicate that the described method is suitable to effectively explore the MHC diversity and its ecological impacts in blue tits in future studies. 相似文献
5.
The great polymorphism observed in the major histocompatibility complex (MHC) genes is thought to be maintained by pathogen-mediated
selection possibly combined with MHC-disassortative mating, guided by MHC-determined olfactory cues. Here, we partly characterize
the MHC class I and II B of the blue petrel, Halobaena caerulea (Procellariiformes), a bird with significant olfactory abilities that lives under presumably low pathogen burdens in Subantarctica.
Blue petrels are long-lived, monogamous birds which suggest the necessity of an accurate mate choice process. The species
is ancestral to songbirds (Passeriformes; many MHC loci), although not to gamefowls (Galliformes; few MHC loci). Considering
the phylogenetic relationships and the low subantarctic pathogen burden, we expected few rather than many MHC loci in the
blue petrel. However, when we analysed partial MHC class I and class II B cDNA and gDNA sequences we found evidence for as
many as at least eight MHC class I loci and at least two class II B loci. These class I and II B sequences showed classical
MHC characteristics, e.g. high nucleotide diversity, especially in putative peptide-binding regions where signatures of positive
selection was detected. Trans-species polymorphism was found between MHC class II B sequences of the blue petrel and those
of thin-billed prion, Pachyptila belcheri, two species that diverged ∼25 MYA. The observed MHC allele richness in the blue petrel may well serve as a basis for mate
choice, especially since olfactory discrimination of MHC types may be possible in this species. 相似文献
6.
Worley K Gillingham M Jensen P Kennedy LJ Pizzari T Kaufman J Richardson DS 《Immunogenetics》2008,60(5):233-247
In species with duplicated major histocompatibility complex (MHC) genes, estimates of genetic variation often rely on multilocus
measures of diversity. It is possible that such measures might not always detect more detailed patterns of selection at individual
loci. Here, we describe a method that allows us to investigate classical MHC diversity in red jungle fowl (Gallus gallus), the wild ancestor of the domestic chicken, using a single locus approach. This is possible due to the well-characterised
gene organisation of the ‘minimal essential’ MHC (BF/BL region) of the domestic chicken, which comprises two differentially
expressed duplicated class I (BF) and two class II B (BLB) genes. Using a combination of reference strand-mediated conformation
analysis, cloning and sequencing, we identify nine BF and ten BLB alleles in a captive population of jungle fowl. We show
that six BF and five BLB alleles are from the more highly expressed locus of each gene, BF2 and BLB2, respectively. An excess of non-synonymous substitutions across the jungle fowl BF/BL region suggests that diversifying selection
has acted on this population. Importantly, single locus screening reveals that the strength of selection is greatest on the
highly expressed BF2 locus. This is the first time that a population of red jungle fowl has been typed at the MHC region,
laying the basis for further research into the underlying processes acting to maintain MHC diversity in this and other species. 相似文献
7.
Gene duplication and gene conversion in class II MHC genes of New Zealand robins (Petroicidae) 总被引:6,自引:6,他引:0
In contrast to mammals, the evolution of MHC genes in birds appears to be characterized by high rates of gene duplication and concerted evolution. To further our understanding of the evolution of passerine MHC genes, we have isolated class II B sequences from two species of New Zealand robins, the South Island robin (Petroica australis australis), and the endangered Chatham Island black robin (Petroica traversi). Using an RT-PCR based approach we isolated four transcribed class II B MHC sequences from the black robin, and eight sequences from the South Island robin. RFLP analysis indicated that all class II B loci were contained within a single linkage group. Analysis of 3-untranslated region sequences enabled putative orthologous loci to be identified in the two species, and indicated that multiple rounds of gene duplication have occurred within the MHC of New Zealand robins. The orthologous relationships are not retained within the coding region of the gene, instead the sequences group within species. A number of putative gene conversion events were identified across the length of our sequences that may account for this. Exon 2 sequences are highly diverse and appear to have diverged under balancing selection. It is also possible that gene conversion involving short stretches of sequence within exon 2 adds to this diversity. Our study is the first report of putative orthologous MHC loci in passerines, and provides further evidence for the importance of gene duplication and gene conversion in the evolution of the passerine MHC.Nucleotide sequence data reported in this paper are available in the GenBank database under the accession numbers AY258333–AY258335, AY428561–AY428570, and AY530534–AY530535 相似文献
8.
Miguel Alcaide Scott V. Edwards Luis Cadahía Juan J. Negro 《Conservation Genetics》2009,10(5):1349-1355
The threat of emerging infectious diseases encourages the investigation of functional loci related to host resilience, such
as those belonging to the major histocompatibility complex (MHC). Through careful primer design targeting to conserved regions
of MHC class I sequences in birds, we successfully amplified a genomic fragment spanning exons 2–4 in three birds of prey.
The identification of a highly conserved region within intron 2 allowed cross-amplifying complete exon 3 sequences in diurnal
raptors, owls and New World vultures. We found evidence through PCR and cloning for 1–2 polymorphic class I loci, although
this is almost certainly an underestimate. Inferences of diversifying selection in the kestrel MHC revealed that the two major
regions of exon 3 exhibiting positive selection mostly agree with those described for the human HLA-A2 molecule. In contrast
to passerines, where a high incidence of gene duplications and pseudogenes has been commonly documented, birds of prey emerge
as nice model species for the investigation of the evolutionary significance and conservation implications of MHC diversity
in vertebrates. 相似文献
9.
10.
Castro-Prieto A Wachter B Melzheimer J Thalwitzer S Sommer S 《The Journal of heredity》2011,102(6):653-665
The genes of the major histocompatibility complex (MHC) are a key component of the mammalian immune system and have become important molecular markers for fitness-related genetic variation in wildlife populations. Currently, no information about the MHC sequence variation and constitution in African leopards exists. In this study, we isolated and characterized genetic variation at the adaptively most important region of MHC class I and MHC class II-DRB genes in 25 free-ranging African leopards from Namibia and investigated the mechanisms that generate and maintain MHC polymorphism in the species. Using single-stranded conformation polymorphism analysis and direct sequencing, we detected 6 MHC class I and 6 MHC class II-DRB sequences, which likely correspond to at least 3 MHC class I and 3 MHC class II-DRB loci. Amino acid sequence variation in both MHC classes was higher or similar in comparison to other reported felids. We found signatures of positive selection shaping the diversity of MHC class I and MHC class II-DRB loci during the evolutionary history of the species. A comparison of MHC class I and MHC class II-DRB sequences of the leopard to those of other felids revealed a trans-species mode of evolution. In addition, the evolutionary relationships of MHC class II-DRB sequences between African and Asian leopard subspecies are discussed. 相似文献
11.
The major histocompatibility complex (MHC) has a central role in the specific immune defence of vertebrates. Exon 3 of MHC class I genes encodes the domain that binds and presents peptides from pathogens that trigger immune reactions. Here we develop a fast population screening method for detecting genetic variation in the MHC class I genes of birds. We found evidence of at least 15 exon 3 sequences in the investigated great reed warbler individual. The organisation of the great reed warbler MHC class I genes suggested that a locus-specific screening protocol is impractical due to the high similarity between alleles across loci, including the introns flanking exon 3. Therefore, we used motif-specific PCR to amplify two subsets of alleles (exon 3 sequences) that were separated with by DGGE. The motif-specific primers amplify a substantial proportion of the transcribed class I alleles (2-12 alleles per individual) from as many as six class I loci. Although not exhaustive, this gives a reliable estimate of the class I variation. The method is highly repeatable and more sensitive in detecting genetic variation than the RFLP method. The motif-specific primers also allow us to avoid screening pseudogenes. In our study population of great reed warblers, we found a high level of genetic variation in MHC class I, and no less than 234 DGGE genotypes were detected among 248 screened individuals. 相似文献
12.
MHC class I genes in a New World primate, the cotton-top tamarin (Saguinus oedipus), have evolved by an active process of loci turnover 总被引:2,自引:2,他引:0
Lymphocytes of a New World primate, the cotton-top tamarin (Saguinus oedipus), express classical G–related major histocompatibility complex (MHC) class I molecules with unusually limited polymorphism and variability. Three
G-related loci, an F locus, an E locus, and two pseudogenes (So-N1 and So-N3) have been identified by cDNA library screening and extensive PCR analysis of both cDNA and genomic DNA from the cotton-top
tamarin. Furthermore, each genus of the subfamily Callitrichinae (tamarins and marmosets) appears to express its own unique
set of MHC class I genes, likely due to a rapid turnover of loci. The rapid emergence of unique MHC class I genes in the Callitrichinae
genera, resulting from an active process of duplication and inactivation of loci, may account for the limited diversity of
the MHC class I genes in the cotton-top tamarin. To determine the nature of the entire complement of MHC class I genes in
the cotton-top tamarin, we synthesized a genomic DNA library and screened it with MHC class I-specific probes. We isolated
nine new MHC class I pseudogenes from this library. These newly isolated tamarin G–related MHC class I pseudogenes are not closely related to any of their functional counterparts in the tamarin, suggesting
that they do not share a recent common ancestral gene with the tamarin's currently expressed MHC class I loci. In addition,
these tamarin sequences display a high rate of nonsynonymous substitutions in their putative peptide binding region. This
indicates that the genes from which they have derived were likely subject to positive selection and, therefore, were once
functional. Our data support the notion that an extremely high rate of loci turnover is largely responsible for the limited
diversity of the MHC class I genes in the cotton-top tamarin.
Received: 15 September 1997 / Revised: 2 July 1998 相似文献
13.
Elizabeth A. Archie Tammy Henry Jesus E. Maldonado Cynthia J. Moss Joyce H. Poole Virginia R. Pearson Suzan Murray Susan C. Alberts Robert C. Fleischer 《Immunogenetics》2010,62(2):85-100
Genes of the vertebrate major histocompatibility complex (MHC) are crucial to defense against infectious disease, provide
an important measure of functional genetic diversity, and have been implicated in mate choice and kin recognition. As a result,
MHC loci have been characterized for a number of vertebrate species, especially mammals; however, elephants are a notable
exception. Our study is the first to characterize patterns of genetic diversity and natural selection in the elephant MHC.
We did so using DNA sequences from a single, expressed DQA locus in elephants. We characterized six alleles in 30 African
elephants (Loxodonta africana) and four alleles in three Asian elephants (Elephas maximus). In addition, for two of the African alleles and three of the Asian alleles, we characterized complete coding sequences
(exons 1–5) and nearly complete non-coding sequences (introns 2–4) for the class II DQA loci. Compared to DQA in other wild
mammals, we found moderate polymorphism and allelic diversity and similar patterns of selection; patterns of non-synonymous
and synonymous substitutions were consistent with balancing selection acting on the peptides involved in antigen binding in
the second exon. In addition, balancing selection has led to strong trans-species allelism that has maintained multiple allelic
lineages across both genera of extant elephants for at least 6 million years. We discuss our results in the context of MHC
diversity in other mammals and patterns of evolution in elephants. 相似文献
14.
Allelic diversity at major histocompatibility complex (MHC) genes is thought to be maintained by balancing selection over long periods of time, even across multiple speciation events. Trans-species sharing of MHC alleles among genera has been supported by many studies on mammals and fish, but in rodents, the results are ambiguous. We investigated natural levels of MHC-DRB variability and evolutionary processes in the wood mouse (Apodemus sylvaticus) and the yellow-necked mouse (Apodemus flavicollis), which are common, sympatric murid rodents in European forests. Using single-strand conformation polymorphism analysis and DNA sequencing, 38 DRB exon 2 alleles were detected among 162 A. sylvaticus from nine different locations in Germany and Switzerland, and 15 DRB exon 2 alleles were detected among 60 A. flavicollis from three different locations in northern Germany. There was evidence for balancing selection in both species. Phylogenetic analysis, including additional murid taxa, showed that the DRB exon 2 sequences did not separate according to species, consistent with trans-species evolution of the MHC in these taxa. 相似文献
15.
Frequent segmental sequence exchanges and rapid gene duplication characterize the<Emphasis Type="Italic"> MHC</Emphasis> class I genes in lemurs 总被引:2,自引:2,他引:0
Go Y Satta Y Kawamoto Y Rakotoarisoa G Randrianjafy A Koyama N Hirai H 《Immunogenetics》2003,55(7):450-461
Major histocompatibility complex (MHC) class I genes have complicated and profound evolutionary histories. To reconstruct and better understand their histories, partial class I genes (exon 2–intron 2–exon 3) were sequenced in a sampling of prosimians (Strepsirhini, Primates). In total, we detected 117 different sequences from 36 Malagasy prosimians (lemurs) and 1 non-Malagasy prosimian (galago) representing 4 families, 7 genera, and 13 species. Unlike the MHC class II genes (MHC-DRB), MHC class I genes show a generally genus-specific mode of evolution in lemurs. Additionally, no prosimian class I loci were found to be orthologous to HLA genes, even at highly conserved loci (such as HLA-E, HLA-F). Phylogenetic analysis indicates that nucleotide diversity among loci was very small and the persistence time of the polymorphisms was short, suggesting that the origin of the lemur MHC class I genes detected in this study was relatively recent. The evolutionary mode of these genes is similar to that of classic HLA genes, HLA-A, HLA-B, and HLA-C, in terms of their recent origin and rarity of pseudogenes, and differs from them with respect to the degree of gene duplications. From the viewpoint of MHC genes evolution, some interlocus sequence exchanges were apparently observed in the lemur lineage upon phylogenetic and amino acid motif analyses. This is also in contrast to the evolutionary mode of HLA genes, where intralocus exchanges have certainly occurred but few interlocus exchanges have taken place. Consequently, the gene conversion model for explaining the generation of the MHC diversity among different loci can be thought to play more important roles in the evolution of lemur MHC class I genes than in that of HLA genes.Electronic Supplementary Material Supplementary material is available in the online version of this article at 相似文献
16.
The genes of the major histocompatibility complex (MHC) are amongst the most variable in vertebrates and represent some of
the best candidates to study processes of adaptive evolution. However, despite the number of studies available, most of the
information on the structure and function of these genes come from studies in mammals and birds in which the MHC class I and
II genes are tightly linked and class II alpha exhibits low variability in many cases. Teleost fishes are among the most primitive
vertebrates with MHC and represent good organisms for the study of MHC evolution because their class I and class II loci are
not physically linked, allowing for independent evolution of both classes of genes. We have compared the diversity and molecular
mechanisms of evolution of classical MH class II α and class II β loci in farm populations of three salmonid species: Oncorhynchus kisutch, Oncorhynchus mykiss and Salmo salar. We found single classical class II loci and high polymorphism at both class II α and β genes in the three species. Mechanisms
of evolution were common for both class II genes, with recombination and point mutation involved in generating diversity and
positive selection acting on the peptide-binding residues. These results suggest that the maintenance of variability at the
class IIα gene could be a mechanism to increase diversity in the MHC class II in salmonids in order to compensate for the
expression of one single classical locus and to respond to a wider array of parasites. 相似文献
17.
Potential links between fish life history traits, an immune investment as measured by variability of the MHC genes and parasitism
were analysed in 14 species of cyprinid fish. The hypothesis of the diversity of MHC genes being driven by high parasite diversity,
i.e. species richness, was tested and a potential relationship between the MHC diversity and fish life-history traits including
adult mortality rate, fecundity, longevity and maturity was investigated. Molecular techniques (SSCP and sequencing) were
applied to analyse the MHC nucleotide diversity of the exons 2 and 3 of DAB genes belonging to the MHC class IIB. The comparative analyses, using phylogenetic independent contrasts, revealed a negative
relationship between parasite species richness and adult fish mortality rate. We also found a positive relationship between
nucleotide diversity of the exon 2 and parasite species richness. Our results suggest that fish species, of which populations
are exposed to high parasite pressure, in terms of high parasite species richness, maintain a high genetic diversity of the
exon 2 of the MHC genes (presenting the peptide binding regions), allowing them to decrease their natural mortality rate. 相似文献
18.
19.
The protein-coding sequences of the major histocompatibility complex (MHC) genes are characterized by extraordinarily high
polymorphism, apparently maintained by balancing selection, which favors diversity in the peptide-binding domains of the MHC
glycoproteins. Here we report that the introns flanking the polymorphic exons of the human MHC class I loci HLA-A, -B, and -C genes have been relatively conserved and have become locus-specific apparently as a result of recombination and subsequent
genetic drift, leading to homogenization within loci over evolutionary time. Thus, HLA class I genes have been shaped by contrasting evolutionary forces maintaining polymorphism in the exons and leading to conservation
in the introns. This study provides the first extensive analysis of the introns of a highly polymorphic gene family.
Received: 10 April 1997 / Revised: 15 July 1997 相似文献
20.
Major histocompatibility complex (MHC) genes are important for vertebrate immune response and typically display high levels
of diversity due to balancing selection from exposure to diverse pathogens. An understanding of the structure of the MHC region
and diversity among functional MHC genes is critical to understanding the evolution of the MHC and species resilience to disease
exposure. In this study, we characterise the structure and diversity of class II MHC genes in little spotted kiwi Apteryx owenii, a ratite bird representing the basal avian lineage (paleognaths). Results indicate that little spotted kiwi have a more
complex MHC structure than that of other non-passerine birds, with at least five class II MHC genes, three of which are expressed
and likely to be functional. Levels of MHC variation among little spotted kiwi are extremely low, with 13 birds assayed having
nearly identical MHC genotypes (only two genotypes containing four alleles, three of which are fixed). These results suggest
that recent genetic drift due to a species-wide bottleneck of at most seven birds has overwhelmed past selection for high
MHC diversity in little spotted kiwi, potentially leaving the species highly susceptible to disease. 相似文献