Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens
Different evolutionary histories of the two classical class I genes BF1 and BF2 illustrate drift and selection within the stable MHC haplotypes of chickens
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DOI：
10.4049/jimmunol.178.9.5744
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发表时间：
2007-05-01
影响因子：
4.4
通讯作者：
Kaufman, Jim
中科院分区：
文献类型：
--
作者：
Shaw, Iain;Powell, Timothy J.;Kaufman, Jim
与典型哺乳动物的MHC相比，B12单倍型的鸡MHC（BF/BL区）更小、更简单、更重排，具有两个经典的I类基因，其中只有一个是高表达的。在这项研究中，我们描述了长距离PCR的发展，分别扩增每个I类基因的部分或全部，使我们能够提出以下几点。首先，其他六种单倍型与B12具有相同的基因组结构，在DMB 2和TAP 2之间具有低表达（次要）BF 1基因，在TAP 2和C4之间具有高表达（主要）BF 2基因。第二，BF 2基因的表达在这些单倍型中以三种不同的方式受损：增强子A缺失（B12，B19），增强子A趋异和转录起始位点缺失（B2，B4，B21），以及插入/重排。导致假基因（B14，B15）。第三，BF 1基因中的三种改变对应于BF 1和低表达II类B（BLB 1）基因的树状图，反映了大多数中性变化，而BF 2和高表达II类（BLB 2）基因的树状图各自具有完全不同的拓扑结构，反映了选择。低表达基因的共同模式反映了BF/BL区域几乎不发生重组的事实，并使我们能够提出这些鸡MHC单倍型来自共同祖先的血统模式。总之，这些数据解释了稳定的MHC单倍型如何主要表达单个I类分子，这反过来又导致鸡MHC与对感染性病原体的抗性和对疫苗的反应的显著关联。免疫学杂志，2007，178：5744-5752.
Compared with the MHC of typical mammals, the chicken MHC (BF/BL region) of the B12 haplotype is smaller, simpler, and rearranged, with two classical class I genes of which only one is highly expressed. In this study, we describe the development of long-distance PCR to amplify some or all of each class I gene separately, allowing us to make the following points. First, six other haplotypes have the same genomic organization as B12, with a poorly expressed (minor) BF1 gene between DMB2 and TAP2 and a well-expressed (major) BF2 gene between TAP2 and C4. Second, the expression of the BF2 gene is crippled in three different ways in these haplotypes: enhancer A deletion (B12, B19), enhancer A divergence and transcription start site deletion (B2, B4, B21), and insertion/rearrangement. leading to pseudogenes (B14, B15). Third, the three kinds of alterations in the BF1 gene correspond to dendrograms of the BF1 and poorly expressed class II B (BLB1) genes reflecting mostly neutral changes, while the dendrograms of the BF2 and well-expressed class II (BLB2) genes each have completely different topologies reflecting selection. The common pattern for the poorly expressed genes reflects the fact the BF/BL region undergoes little recombination and allows us to propose a pattern of descent for these chicken MHC haplotypes from a common ancestor. Taken together, these data explain how stable MHC haplotypes predominantly express a single class I molecule, which in turn leads to striking associations of the chicken MHC with resistance to infectious pathogens and response to vaccines. The Journal of Immunology, 2007, 178: 5744-5752.