In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function
The major histocompatibility complex (MHC) genes are the most polymorphic genes found in the vertebrate genome, and they encode proteins that play an essential role in the adaptive immune response. Many songbirds (passerines) have been shown to have a large number of transcribed MHC class I genes compared to most mammals. To elucidate the reason for this large number of genes, we compared 14 MHC class I alleles (α1–α3 domains), from great reed warbler, house sparrow and tree sparrow, via phylogenetic analysis, homology modelling and in silico peptide-binding predictions to investigate their functional and genetic relationships. We found more pronounced clustering of the MHC class I allomorphs (allele specific proteins) in regards to their function (peptide-binding specificities) compared to their genetic relationships (amino acid sequences), indicating that the high number of alleles is of functional significance. The MHC class I allomorphs from house sparrow and tree sparrow, species that diverged 10 million years ago (MYA), had overlapping peptide-binding specificities, and these similarities across species were also confirmed in phylogenetic analyses based on amino acid sequences. Notably, there were also overlapping peptide-binding specificities in the allomorphs from house sparrow and great reed warbler, although these species diverged 30 MYA. This overlap was not found in a tree based on amino acid sequences. Our interpretation is that convergent evolution on the level of the protein function, possibly driven by selection from shared pathogens, has resulted in allomorphs with similar peptide-binding repertoires, although trans-species evolution in combination with gene conversion cannot be ruled out.
KeywordsMajor histocompatibility complex (MHC) class I Functional clustering Convergent evolution Trans-species evolution Gene conversion Passerine birds
This study was financed by grants from the Swedish Research Council, Crafoords foundation and Schybergs foundation (the Royal Physiographic foundation) to Helena Westerdahl, by grants from the Swedish Research Council to Stefan Wallin, by grants from the Swedish Research Council, Kocks foundation, Crafoords foundation, the Royal Physiographic foundation, Groschinskys foundation and Alfred Österlunds foundation to Kajsa Paulsson, and by grants from the foundation of ‘Regementsläkaren Dr Hartelii’ to Elna Follin. We would like to thank Anna Drews and Ester Arévalo Sureda for assistance in the lab and Emily O´Connor and three anonymous referees for giving feedback on the manuscript.
Conflict of interest
The authors declare that they have no conflict of interest.
- Axelsson-Robertson R, Ahmed RK, Weichold FF, Ehlers MM, Kock MM, Sizemore D, Sadoff J, Maeurer M (2011) Human leukocyte antigens A*3001 and A*3002 show distinct peptide-binding patterns of the Mycobacterium tuberculosis protein TB10.4: consequences for immune recognition. Clin vaccine immunol CVI 18:125–134CrossRefGoogle Scholar
- Cramp S (1992) Handbook of the birds of Europe, the Middle East and North Africa. Oxford University Press, OxfordGoogle Scholar
- Hall TA (1999) BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 41:95–98Google Scholar
- Koch M, Camp S, Collen T, Avila D, Salomonsen J, Wallny HJ, van Hateren A, Hunt L, Jacob JP, Johnston F, Marston DA, Shaw I, Dunbar PR, Cerundolo V, Jones EY, Kaufman J (2007) Structures of an MHC class I molecule from B21 chickens illustrate promiscuous peptide binding. Immunity 27:885–899PubMedCrossRefGoogle Scholar
- Nielsen M, Lund O, Lundegaard C (2012) MHCcluster, a method for functional clustering of MHC molecules. ISCB-LatinGoogle Scholar
- Shaw I, Powell TJ, Marston DA, Baker K, van Hateren A, Riegert P, Wiles MV, Milne S, Beck S, Kaufman J (2007) Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens. J Immunol 178:5744–5752PubMedGoogle Scholar
- Stearns SC, Koella JC (2007) Evolution in health and disease. Oxford University Press, New YorkGoogle Scholar
- Thomsen MC, Nielsen M (2012) Seq2Logo: a method for construction and visualization of amino acid binding motifs and sequence profiles including sequence weighting, pseudo counts and two-sided representation of amino acid enrichment and depletion. Nucleic acids resGoogle Scholar
- Wallny HJ, Avila D, Hunt LG, Powell TJ, Riegert P, Salomonsen J, Skjodt K, Vainio O, Vilbois F, Wiles MV, Kaufman J (2006) Peptide motifs of the single dominantly expressed class I molecule explain the striking MHC-determined response to Rous sarcoma virus in chickens. Proc Natl Acad Sci USA 103:1434–1439PubMedCrossRefGoogle Scholar
- Warren WC, Clayton DF, Ellegren H, Arnold AP, Hillier LW, Kunstner A, Searle S, White S, Vilella AJ, Fairley S, Heger A, Kong L, Ponting CP, Jarvis ED, Mello CV, Minx P, Lovell P, Velho TA, Ferris M, Balakrishnan CN, Sinha S, Blatti C, London SE, Li Y, Lin YC, George J, Sweedler J, Southey B, Gunaratne P, Watson M, Nam K, Backstrom N, Smeds L, Nabholz B, Itoh Y, Whitney O, Pfenning AR, Howard J, Volker M, Skinner BM, Griffin DK, Ye L, McLaren WM, Flicek P, Quesada V, Velasco G, Lopez-Otin C, Puente XS, Olender T, Lancet D, Smit AF, Hubley R, Konkel MK, Walker JA, Batzer MA, Gu W, Pollock DD, Chen L, Cheng Z, Eichler EE, Stapley J, Slate J, Ekblom R, Birkhead T, Burke T, Burt D, Scharff C, Adam I, Richard H, Sultan M, Soldatov A, Lehrach H, Edwards SV, Yang SP, Li X, Graves T, Fulton L, Nelson J, Chinwalla A, Hou S, Mardis ER, Wilson RK (2010) The genome of a songbird. Nature 464:757–762PubMedCrossRefGoogle Scholar
- Yang Z (1997) PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci CABIOS 13:555–556Google Scholar