Department of Pathology and Laboratory Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Hum Immunol. 2010 Sep;71(9):837-42. doi: 10.1016/j.humimm.2010.06.010. Epub 2010 Jun 19.
Class I human leukocyte antigen (HLA) alleles can be classified into supertypes based on the epitope specificity of their peptide binding grooves. The evolutionary origin of these supertypes has been the topic of prior research and remains an important question because of the increasing interest in HLA supertypes in the contexts of infection and cancer epidemiology and vaccine development. Here I re-examine the origins of HLA class I supertypes using the nucleotide sequences of 88 HLA-A alleles and 117 HLA-B alleles. Phylogenetic trees with ancestral character state reconstruction show that the HLA-A02, A03, and A24 supertypes largely form clades with a single ancestral origin while HLA-A01 shows multiple independent origins all from HLA-A03 ancestors. HLA-B supertypes show multiple origins for the B07, B08, and B27 supertypes, while the B44, B58, and B62 supertypes largely form clades with a single ancestor. Supertypes arising multiple times show different amino acid substitutions in each clade. These findings suggest that convergent evolution has occurred in only a few HLA allele supertypes and may indicate different evolutionary pressures shaping certain supertypes.
I 类人类白细胞抗原 (HLA) 等位基因可根据其肽结合槽的表位特异性分为超型。这些超型的进化起源一直是先前研究的主题，由于人们越来越关注感染和癌症流行病学以及疫苗开发背景下的 HLA 超型，因此这个问题仍然很重要。在这里，我使用 88 个 HLA-A 等位基因和 117 个 HLA-B 等位基因的核苷酸序列重新研究了 HLA I 类超型的起源。带有祖先特征状态重建的系统发育树表明，HLA-A02、A03 和 A24 超型主要形成具有单一祖先起源的分支，而 HLA-A01 则显示出多种独立起源，均来自 HLA-A03 祖先。HLA-B 超型的 B07、B08 和 B27 超型显示出多种起源，而 B44、B58 和 B62 超型则主要形成具有单一祖先的分支。多次出现的超型在每个分支中显示出不同的氨基酸取代。这些发现表明，只有少数 HLA 等位基因超型发生了趋同进化，这可能表明某些超型受到了不同的进化压力的影响。
