Wu S, Saunders T L, Bach F H
Nature. 1986;324(6098):676-9. doi: 10.1038/324676a0.
Class II molecules encoded by the human major histocompatibility complex (MHC) are involved in regulating T-cell response to antigens. The mechanisms for generating polymorphism in products of the MHC have been studied extensively for both the murine H-2 and the human HLA complex. Such studies indicate that point mutations plus selection have a major role in the generation of polymorphisms of class I and class II MHC genes. However, a non-reciprocal gene conversion mechanism has been proposed to explain several examples of clustered sequence variation in MHC genes. In all these examples, the proposed gene conversion event is unidirectional; that is, one of the two interacting genes acts as sequence donor and the other as sequence recipient. No examples of potential reciprocal genetic exchange (as occurs in the fungal system), in which the two interacting genes act as both donor and recipient of gene fragments, have been found in the MHC system or in other multigene families of higher organisms. We sequenced two different HLA-DR beta complementary DNAs from each of two different cells all expressing the same serologically defined determinant (DR2) but different T-cell-recognized (Dw) specificities (Dw12 and MN2). Sequence comparisons of these four cDNA clones (and two DR beta amino-acid sequences from the DR2-Dw2 subtype) suggest that new coding sequences for DR beta molecules in the DR2 haplotypes are potentially generated by reciprocal intergenic exchange.
人类主要组织相容性复合体（MHC）编码的II类分子参与调节T细胞对抗原的反应。对于小鼠的H-2复合体和人类的HLA复合体，人们已经广泛研究了MHC产物产生多态性的机制。此类研究表明，点突变加上选择在I类和II类MHC基因多态性的产生中起主要作用。然而，有人提出一种非相互基因转换机制来解释MHC基因中几个成簇序列变异的例子。在所有这些例子中，所提出的基因转换事件是单向的；也就是说，两个相互作用的基因之一作为序列供体，另一个作为序列受体。在MHC系统或高等生物的其他多基因家族中，尚未发现潜在的相互基因交换的例子（如在真菌系统中发生的那样），即两个相互作用的基因同时作为基因片段的供体和受体。我们从两个不同的细胞中分别测序了两种不同的HLA-DRβ互补DNA，这两个细胞均表达相同的血清学定义决定簇（DR2），但具有不同的T细胞识别（Dw）特异性（Dw12和MN2）。对这四个cDNA克隆（以及来自DR2-Dw2亚型的两个DRβ氨基酸序列）的序列比较表明，DR2单倍型中DRβ分子的新编码序列可能是由相互基因间交换产生的。
