Steele Edward J
Perspect Biol Med. 2014 Spring;57(2):179-97. doi: 10.1353/pbm.2014.0014.
The major histocompatibility complex (MHC), once labelled the "sphinx of immunology" by Jan Klein, provides powerful challenges to evolutionary thinking. This essay highlights the main discoveries that established the block ancestral haplotype structure of the MHC and the wider genome, focusing on the work by the Perth (Australia) group, led by Roger Dawkins, and the Boston group, led by Chester Alper and Edmond Yunis. Their achievements have been overlooked in the rush to sequence the first and subsequent drafts of the human genome. In Caucasoids, where most of the detailed work has been done, about 70% of all known allelic MHC diversity can be accounted for by 30 or so ancestral haplotypes (AHs), or conserved sequences of many mega-bases, and their recombinants. The block haplotype structure of the genome, as shown for the MHC (and other genetic regions), is a story that needs to be understood in its own right, particularly given the promotion of the "HapMap" project and single nucleotide polymorphism (SNP) linkage disequilibrium (LD) analysis, which has been wrongly touted as the only way to pinpoint those genes that are important in genetic disorders or other desired (qualitative) characteristics.
主要组织相容性复合体（MHC），曾被扬·克莱因称为“免疫学的斯芬克斯”，给进化思维带来了巨大挑战。本文着重介绍了确定MHC以及更广泛基因组的嵌合祖先单倍型结构的主要发现，重点关注由罗杰·道金斯领导的珀斯（澳大利亚）团队以及由切斯特·阿尔珀和埃德蒙·尤尼斯领导的波士顿团队所开展的工作。在匆忙对人类基因组的初稿及后续版本进行测序的过程中，他们的成就被忽视了。在大多数详细研究工作都已完成的高加索人中，所有已知的MHC等位基因多样性中，约70%可由30个左右的祖先单倍型（AHs），即许多兆碱基的保守序列及其重组体来解释。正如MHC（以及其他基因区域）所显示的那样，基因组的嵌合单倍型结构本身就是一个需要被理解的故事，特别是考虑到“国际人类基因组单体型图计划”以及单核苷酸多态性（SNP）连锁不平衡（LD）分析的推广，而后者被错误地吹捧为确定那些在遗传疾病或其他期望的（定性）特征中起重要作用的基因的唯一方法。
