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Published in final edited form as: Nat Rev Immunol. 2013 Jan 21;13(2):133–144. doi: 10.1038/nri3370

a | Humans first entered the Americas at Alaska after migration from Asia ~17,000 years ago. North, Central and South America were then colonized by southward migration. For present-day Native American populations of North America, the HLA-B alleles largely remain identical to the ones that came with the migrants from Asia. Starting in the southwestern part of the USA and increasing with distance southwards, the Amerindian populations have ‘new’ recombinant HLA-B alleles in which a short sequence segment in one Asian founder allele was replaced by the orthologous segment from another founder allele. This phenomenon is illustrated for the HLA-B*35:01 Asian allele⁹². Shown are fourteen recombinants of HLA-B*35:01, the amino-acid positions that were affected by the recombinations, and the various founder alleles that could have been the donor for the recombinations. All such recombinations involve one or more amino-acid substitutions in the α₁ and α₂ domains that alter the interactions of HLA-B with antigenic peptides (p) and T-cell receptors (t). For each recombination the potential donor alleles are indicated by the coloured boxes on the right and the donated sequences by the coloured residue boxes on the left. For the six recombinations with more than one possible donor, the residues are only shaded with the colour of one of them (the one furthest to the left). b | The ‘heat map’ shows the geographical distribution of the archaic allele HLA-B*73. The colour spectrum denotes increasing frequency from 0% (dark blue) to 4.5% (bright red). Gray shading indicates regions for which high-resolution HLA typing data from ethnically well-defined indigenous populations were not available. The table below the heat map shows the 41 amino-acid differences that distinguish HLA-B*35:01 and HLA-B*73:01. Of these 16 are at functionally important positions that make contact with peptide (p), T-cell receptor (t), KIR (k) or leukocyte immunoglobulin-like receptor (l).

a | Humans first entered the Americas at Alaska after migration from Asia ~17,000 years ago. North, Central and South America were then colonized by southward migration. For present-day Native American populations of North America, the HLA-B alleles largely remain identical to the ones that came with the migrants from Asia. Starting in the southwestern part of the USA and increasing with distance southwards, the Amerindian populations have ‘new’ recombinant HLA-B alleles in which a short sequence segment in one Asian founder allele was replaced by the orthologous segment from another founder allele. This phenomenon is illustrated for the HLA-B*35:01 Asian allele⁹². Shown are fourteen recombinants of HLA-B*35:01, the amino-acid positions that were affected by the recombinations, and the various founder alleles that could have been the donor for the recombinations. All such recombinations involve one or more amino-acid substitutions in the α₁ and α₂ domains that alter the interactions of HLA-B with antigenic peptides (p) and T-cell receptors (t). For each recombination the potential donor alleles are indicated by the coloured boxes on the right and the donated sequences by the coloured residue boxes on the left. For the six recombinations with more than one possible donor, the residues are only shaded with the colour of one of them (the one furthest to the left). b | The ‘heat map’ shows the geographical distribution of the archaic allele HLA-B*73. The colour spectrum denotes increasing frequency from 0% (dark blue) to 4.5% (bright red). Gray shading indicates regions for which high-resolution HLA typing data from ethnically well-defined indigenous populations were not available. The table below the heat map shows the 41 amino-acid differences that distinguish HLA-B*35:01 and HLA-B*73:01. Of these 16 are at functionally important positions that make contact with peptide (p), T-cell receptor (t), KIR (k) or leukocyte immunoglobulin-like receptor (l).