Vallejo A N, Pease L R
Department of Immunology, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
J Immunol. 1995 Apr 15;154(8):3912-21.
The expansion and contraction of mammalian class I multigene families raises the issue as to what determines the loss or retention of family members. We propose that accumulating changes in regulatory regions result in the loss of expression of the gene products during times critical to selection, leading to the extinction of misregulated genes. The structures of promoter regions of MHC class I genes in nonhuman primates support this view. The B promoters are more homogeneous and contain regulatory elements also found in the promoters of the homologous class I genes of more distant mammals, whereas the A locus promoters were significantly more heterogeneous, have fewer sequence motifs related to known transcription factor-binding sites and have accumulated nucleotide substitutions within one of the widely conserved class I promoter elements. These findings are consistent with the view that the more polymorphic B locus is the principal MHC locus encoding functional class I Ag-presenting molecules whereas the less polymorphic A locus is assuming a secondary role as a consequence of promoter defects.
哺乳动物I类多基因家族的扩增和收缩引发了一个问题，即是什么决定了家族成员的丢失或保留。我们提出，调控区域累积的变化导致基因产物在对选择至关重要的时期失去表达，从而导致调控异常的基因灭绝。非人类灵长类动物MHC I类基因启动子区域的结构支持这一观点。B启动子更为同质化，包含在更远亲缘关系哺乳动物的同源I类基因启动子中也发现的调控元件，而A位点启动子则明显更具异质性，与已知转录因子结合位点相关的序列基序更少，并且在一个广泛保守的I类启动子元件内积累了核苷酸替换。这些发现与以下观点一致，即多态性更高的B位点是编码功能性I类抗原呈递分子的主要MHC位点，而多态性较低的A位点由于启动子缺陷而发挥次要作用。
