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Table 3 Comparing sequence polymorphism and strength of selection between MHC classes using both peptide binding domains

From: High functional allelic diversity and copy number in both MHC classes in the common buzzard

Species

MHC region

nalleles

Pi

dN/dS

dN-dS

SE

Z-score

P

Human

HLA-I exon 2 (α1)

83

0.087

3.160

0.203

0.081

0.728

0.233

HLA-I exon 3 (α2)

83

0.065

2.447

0.123

0.076

0.052

0.479

HLA-I exon 2 & 3 (α1α2)

83

0.076

2.809

0.161

0.054

1.565

0.059

HLA-II DRA exon 2 (α1)

1

0.000

NA

0.000

0.000

  

HLA-II DRB1 exon 2 (β1)

29

0.062

1.922

0.117

0.086

  

HLA-II DR- A & B1 exon 2 (α1β1)

29

0.033

1.750

0.050

0.046

  

Common buzzard

MHC-I exon 2 (α1)

10

0.094

3.461

0.219

0.075

-1.147

0.126

MHC-I exon 3 (α2)

8

0.065

2.635

0.121

0.059

-2.042

0.021

MHC-I exon 2 & 3 (α1α2)

10

0.079

3.089

0.166

0.042

-0.143

0.443

MHC-IIA exon 2 (α1)

3

0.008

NA

0.035

0.036

  

MHC-IIB exon 2 (β1)

8

0.105

9.156

0.367

0.105

  

MHC-II A & B exon 2 (α1β1)

8

0.056

7.481

0.175

0.047

  
  1. To demonstrate how a false conclusion can be reached when comparing only one set of peptide binding domains between MHC classes, we collected and analyzed well-curated alleles from humans and full alleles of common buzzards. Human class I HLA-A, B, C, and class II HLA-DRB1 alleles from the European population classified as "common" in the Common and Well-Documented allele catalog 3.0.0 [70] as well as HLA-DRA*01:01 from the monomorphic DRA locus were downloaded from IPD-IMGT/HLA Database version 3.51 [16] (Additional file Table S5). Common buzzard alleles with full peptide-binding grooves were retrieved from genomic data (GenBank accession #s: OL311287, OL311290, OL311292, OL311294, OL311304, OL311305, OP490259, OQ414190-OQ414202, OQ428163-OQ428174). All analyses for the strength of selection (dN and dS) were conducted in MEGA X [71] using human peptide binding residues from [72] and the Nei-Gojobori model [73] with 1000 bootstraps for variance estimation. The Z-score was calculated with the formula (dN-dSMHC-I—dN-dSMHC-II)/\(\surd\)(SE2MHC-I + SE2MHC-II). We compared MHC-I exon 2 and 3 separately with MHC-IIB exon 2, and then combined against concatenated MHC-IIA & B exon 2 sequences. We tested if MHC-I had stronger selection than MHC-II in humans and if MHC-IIB had stronger selection than MHC-I in common buzzards. One-sided p-values were generated from the Z-scores. P-values show how comparing single exons between the classes does not represent comparisons across the full binding domains (italicized for emphasis; MHC-I: α1α2, MHC-II: α1β1). nalleles: number of alleles, Pi: nucleotide diversity, SE: standard error of the mean. Significant p-values are highlighted in bold