In silico peptide-binding predictions of passerine MHC class I reveal similarities across distantly related species, suggesting convergence on the level of protein function
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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.
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