Diversity and selection of MHC class I genes in the Godlewski's bunting

The major histocompatibility complex (MHC) is a multiple-copy immune gene family in vertebrates. Its genes are highly variable and code for antigen-presenting molecules. Characterization of MHC genes in different species and investigating the mechanisms that shape MHC diversity is an important goal in understanding the evolution of biological diversity. Here we developed a next generation sequencing (NGS) protocol to genotype the MHC class I genes of 326 Godlewski’s buntings (Emberiza godlewskii) sampled in the Western mountain area of Beijing from 2014 to 2016. A total of 184 functional alleles were identified, including both non-classical and classical alleles. Classical alleles could be clustered into nine supertypes. Compared with other passerine birds, the individual diversity of MHC class I genes in Godlewski’s buntings is intermediate. Ten amino acid sites in the antigen-binding domain showed signatures of positive selection and eight of them exhibit high amino acid polymorphism. These findings indicate the action of balancing selection and provide a framework for subsequent investigation of selection acting on MHC genes in Godlewski’s buntings.

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Allelic diversity and patterns of selection at the major histocompatibility complex class I and II loci in a threatened shorebird, the Snowy Plover (Charadrius nivosus)

BMC Evolutionary Biology ◽

10.1186/s12862-020-01676-7 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Medardo Cruz-López ◽

Guillermo Fernández ◽

Helen Hipperson ◽

Eduardo Palacios ◽

John Cavitt ◽

...

Keyword(s):

Mhc Class I ◽

Mhc Class Ii ◽

Balancing Selection ◽

Allelic Diversity ◽

Class Ii ◽

Class I ◽

Mhc Genes ◽

Snowy Plover ◽

Snowy Plovers ◽

Private Alleles

Abstract Background Understanding the structure and variability of adaptive loci such as the major histocompatibility complex (MHC) genes is a primary research goal for evolutionary and conservation genetics. Typically, classical MHC genes show high polymorphism and are under strong balancing selection, as their products trigger the adaptive immune response in vertebrates. Here, we assess the allelic diversity and patterns of selection for MHC class I and class II loci in a threatened shorebird with highly flexible mating and parental care behaviour, the Snowy Plover (Charadrius nivosus) across its broad geographic range. Results We determined the allelic and nucleotide diversity for MHC class I and class II genes using samples of 250 individuals from eight breeding population of Snowy Plovers. We found 40 alleles at MHC class I and six alleles at MHC class II, with individuals carrying two to seven different alleles (mean 3.70) at MHC class I and up to two alleles (mean 1.45) at MHC class II. Diversity was higher in the peptide-binding region, which suggests balancing selection. The MHC class I locus showed stronger signatures of both positive and negative selection than the MHC class II locus. Most alleles were present in more than one population. If present, private alleles generally occurred at very low frequencies in each population, except for the private alleles of MHC class I in one island population (Puerto Rico, lineage tenuirostris). Conclusion Snowy Plovers exhibited an intermediate level of diversity at the MHC, similar to that reported in other Charadriiformes. The differences found in the patterns of selection between the class I and II loci are consistent with the hypothesis that different mechanisms shape the sequence evolution of MHC class I and class II genes. The rarity of private alleles across populations is consistent with high natal and breeding dispersal and the low genetic structure previously observed at neutral genetic markers in this species.

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The strength of selection is consistent across both domains of the MHC class I peptide-binding groove in birds

BMC Ecology and Evolution ◽

10.1186/s12862-021-01812-x ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Piotr Minias ◽

Ke He ◽

Peter O. Dunn

Keyword(s):

Mhc Class I ◽

Peptide Binding ◽

Variable Region ◽

Molecular Data ◽

Class I ◽

Amino Acid Polymorphism ◽

Exon 2 ◽

Peptide Binding Groove ◽

Binding Groove ◽

Avian Mhc

Abstract Background The Major Histocompatibility Complex (MHC) codes for the key vertebrate immune receptors responsible for pathogen recognition. Foreign antigens are recognized via their compatibility to hyper-variable region of the peptide-binding groove (PBR), which consists of two separate protein domains. Specifically, the PBR of the MHC class I receptors, which recognize intra-cellular pathogens, has two α domains encoded by exon 2 (α1) and exon 3 (α2) of the same gene. Most research on avian MHC class I polymorphism has traditionally focused exclusively on exon 3 and comparisons of selection between the two domains have been hampered by the scarcity of molecular data for exon 2. Thus, it is not clear whether the two domains vary in their specificity towards different antigens and whether they are subject to different selective pressure. Results Here, we took advantage of rapidly accumulating genomic resources to test for the differences in selection patterns between both MHC class I domains of the peptide-binding groove in birds. For this purpose, we compiled a dataset of MHC class I exon 2 and 3 sequences for 120 avian species from 46 families. Our phylogenetically-robust approach provided strong evidence for highly consistent levels of selection on the α1 and α2 domains. There were strong correlations in all selection measures (number of positively/negatively selected residues and dN/dS ratios) between both PBR exons. Similar positive associations were found for the level of amino acid polymorphism across the two domains. Conclusions We conclude that the strength of selection and the level of polymorphism are highly consistent between both peptide-binding domains (α1 and α2) of the avian MHC class I.

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PAAQD: Predicting immunogenicity of MHC class I binding peptides using amino acid pairwise contact potentials and quantum topological molecular similarity descriptors

Journal of Immunological Methods ◽

10.1016/j.jim.2012.09.016 ◽

2013 ◽

Vol 387 (1-2) ◽

pp. 293-302 ◽

Cited By ~ 14

Author(s):

Thammakorn Saethang ◽

Osamu Hirose ◽

Ingorn Kimkong ◽

Vu Anh Tran ◽

Xuan Tho Dang ◽

...

Keyword(s):

Amino Acid ◽

Mhc Class I ◽

Molecular Similarity ◽

Class I ◽

Binding Peptides

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Impaired MHC class I (H-2Dd)-mediated protection against Ly-49A+ NK cells after amino acid substitutions in the antigen binding cleft

European Journal of Immunology ◽

10.1002/(sici)1521-4141(199809)28:09<2872::aid-immu2872>3.0.co;2-3 ◽

1998 ◽

Vol 28 (9) ◽

pp. 2872-2881 ◽

Cited By ~ 14

Author(s):

Margareta Waldenström ◽

Jonas Sundbäck ◽

Mats Y. Olsson-Alheim ◽

Adnane Achour ◽

Klas Kärre

Keyword(s):

Amino Acid ◽

Nk Cells ◽

Mhc Class I ◽

Class I ◽

Antigen Binding ◽

Amino Acid Substitutions ◽

Binding Cleft

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Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression

Scientific Reports ◽

10.1038/srep13994 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 5

Author(s):

Megumi Tasaka-Fujita ◽

Nao Sugiyama ◽

Wonseok Kang ◽

Takahiro Masaki ◽

Asako Murayama ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Amino Acid ◽

Mhc Class I ◽

Infectious Virus ◽

Core Protein ◽

Virus Production ◽

Class I ◽

Histocompatibility Complex

Abstract Amino acid (aa) polymorphisms in the hepatitis C virus (HCV) genotype 1b core protein have been reported to be a potent predictor for poor response to interferon (IFN)-based therapy and a risk factor for hepatocarcinogenesis. We investigated the effects of these polymorphisms with genotype 1b/2a chimeric viruses that contained polymorphisms of Arg/Gln at aa 70 and Leu/Met at aa 91. We found that infectious virus production was reduced in cells transfected with chimeric virus RNA that had Gln at aa 70 (aa70Q) compared with RNA with Arg at aa 70 (aa70R). Using flow cytometry analysis, we confirmed that HCV core protein accumulated in aa70Q clone transfected cells and it caused a reduction in cell-surface expression of major histocompatibility complex (MHC) class I molecules induced by IFN treatment through enhanced protein kinase R phosphorylation. We could not detect any effects due to the polymorphism at aa 91. In conclusion, the polymorphism at aa 70 was associated with efficiency of infectious virus production and this deteriorated virus production in strains with aa70Q resulted in the intracellular accumulation of HCV proteins and attenuation of MHC class I molecule expression. These observations may explain the strain-associated resistance to IFN-based therapy and hepatocarcinogenesis of HCV.

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Evaluation of T-cell responses to peptides and lipopeptides with MHC class I binding motifs derived from the amino acid sequence of the 19-kDa lipoprotein of Mycobacterium tuberculosis

Molecular Immunology ◽

10.1016/s0161-5890(00)00066-3 ◽

2000 ◽

Vol 37 (8) ◽

pp. 413-422 ◽

Cited By ~ 9

Author(s):

Dora P.A.J Fonseca ◽

Dianne Joosten ◽

Harm Snippe ◽

André F.M Verheul

Keyword(s):

Mycobacterium Tuberculosis ◽

Amino Acid ◽

T Cell ◽

Amino Acid Sequence ◽

Mhc Class I ◽

T Cell Responses ◽

Class I ◽

Binding Motifs ◽

Cell Responses

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H-2Kd-restricted antigenic peptides share a simple binding motif.

Journal of Experimental Medicine ◽

10.1084/jem.174.3.603 ◽

1991 ◽

Vol 174 (3) ◽

pp. 603-612 ◽

Cited By ~ 93

Author(s):

P Romero ◽

G Corradin ◽

I F Luescher ◽

J L Maryanski

Keyword(s):

Amino Acid ◽

Mhc Class I ◽

Specific Binding ◽

Structural Features ◽

Class I ◽

Binding Motif ◽

Antigenic Peptides ◽

Amino Acid Residues ◽

Antigenic Activity ◽

Mhc Class I Molecule

We have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (MHC) class I molecule, H-2Kd. The four epitopes are recognized in the form of synthetic peptides by cytotoxic T lymphocytes of the appropriate specificity. By analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 or 10 amino acid residues. A comparison of the relative competitor activity of the different-length peptides in a functional competition assay, as well as in a direct binding assay based on photoaffinity labeling of the Kd molecule, indicated that the enhanced potency of the peptides upon reduction in length was most likely due to a higher affinity of the shorter peptides for the Kd molecule. A remarkably simple motif that appears to be important for the specific binding of Kd-restricted peptides was identified by the analysis of peptides containing amino acid substitutions or deletions. The motif consists of two elements, a Tyr in the second position relative to the NH2 terminus and a hydrophobic residue with a large aliphatic side chain (Leu, Ile, or Val) at the COOH-terminal end of the optimal 9- or 10-mer peptides. We demonstrated that a simple peptide analogue (AYP6L) that incorporates the motif can effectively and specifically interact with the Kd molecule. Moreover, all of the additional Kd-restricted epitopes defined thus far in the literature contain the motif, and it may thus be useful for the prediction of new epitopes recognized by T cells in the context of this MHC class I molecule.

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Effect of a Single Amino Acid Change in MHC Class I Molecules on the Rate of Progression to AIDS

New England Journal of Medicine ◽

10.1056/nejm200105313442203 ◽

2001 ◽

Vol 344 (22) ◽

pp. 1668-1675 ◽

Cited By ~ 346

Author(s):

Xiaojiang Gao ◽

George W. Nelson ◽

Peter Karacki ◽

Maureen P. Martin ◽

John Phair ◽

...

Keyword(s):

Amino Acid ◽

Mhc Class I ◽

Amino Acid Change ◽

Class I ◽

Single Amino Acid ◽

Single Amino Acid Change ◽

Rate Of Progression ◽

Mhc Class I Molecules

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Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1918232117 ◽

2020 ◽

Vol 117 (10) ◽

pp. 5376-5385 ◽

Cited By ~ 4

Author(s):

Joaquin C. B. Nunez ◽

Patrick A. Flight ◽

Kimberly B. Neil ◽

Stephen Rong ◽

Leif A. Eriksson ◽

...

Keyword(s):

Amino Acid ◽

Balancing Selection ◽

Amino Acid Polymorphism ◽

Intertidal Zones ◽

Spatial And Temporal Scales ◽

Allelic Replacement ◽

Mannose 6 Phosphate ◽

A Site ◽

Zonation Patterns ◽

Insight Into

The mannose-6-phosphate isomerase (Mpi) locus in Semibalanus balanoides has been studied as a candidate gene for balancing selection for more than two decades. Previous work has shown that Mpi allozyme genotypes (fast and slow) have different frequencies across Atlantic intertidal zones due to selection on postsettlement survival (i.e., allele zonation). We present the complete gene sequence of the Mpi locus and quantify nucleotide polymorphism in S. balanoides, as well as divergence to its sister taxon Semibalanus cariosus. We show that the slow allozyme contains a derived charge-altering amino acid polymorphism, and both allozyme classes correspond to two haplogroups with multiple internal haplotypes. The locus shows several footprints of balancing selection around the fast/slow site: an enrichment of positive Tajima’s D for nonsynonymous mutations, an excess of polymorphism, and a spike in the levels of silent polymorphism relative to silent divergence, as well as a site frequency spectrum enriched for midfrequency mutations. We observe other departures from neutrality across the locus in both coding and noncoding regions. These include a nonsynonymous trans-species polymorphism and a recent mutation under selection within the fast haplogroup. The latter suggests ongoing allelic replacement of functionally relevant amino acid variants. Moreover, predicted models of Mpi protein structure provide insight into the functional significance of the putatively selected amino acid polymorphisms. While footprints of selection are widespread across the range of S. balanoides, our data show that intertidal zonation patterns are variable across both spatial and temporal scales. These data provide further evidence for heterogeneous selection on Mpi.

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