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I类主要组织相容性复合体抗原mRNA的结构与多态性

Structure and polymorphism of class I MHC antigen mRNA.

作者信息

Sood A K, Pan J, Biro P A, Pereira D, Srivastava R, Reddy V B, Duceman B W, Weissman S M

出版信息

Immunogenetics. 1985;22(2):101-21. doi: 10.1007/BF00563508.

DOI:10.1007/BF00563508
PMID:2993161
Abstract

We have used cDNA cloning and primer extension techniques to determine the complete nucleotide sequence of HLA-B7 mRNA. The 5'-untranslated sequence of the mRNA is rather short and the putative promoter has weak homology to the conventional "TATA" sequences. The 5' end and the polyadenylation site define the transcription unit of the B7 gene to be about 3.5 kb long. Comparison of the translated nucleotide sequence of this cDNA with the amino acid sequence of the heavy chain of the B7 antigen showed two amino acid differences. In addition, comparison with the sequences of the coding and untranslated regions of several HLA and H-2 genes showed that the class I histocompatibility molecules consist of four variable segments separated by three regions of homology. Analysis of the DNA polymorphisms revealed that in the variable segments the majority of the nucleotide substitutions are nonsilent, while in the homology regions the majority of substitutions are silent. Further analysis of the nature of the amino acid substitutions revealed the predominance of nonconservative replacements/changes in both the variable segments and the homology regions except the transmembrane part of the molecule. Selection at both the protein and the codon levels contributes to the pattern of mutations found in class I histocompatibility molecules.

摘要

我们利用cDNA克隆和引物延伸技术确定了HLA - B7 mRNA的完整核苷酸序列。该mRNA的5'-非翻译序列相当短,其推测的启动子与传统的“TATA”序列的同源性较弱。5'端和聚腺苷酸化位点确定B7基因的转录单位约为3.5 kb长。将该cDNA的翻译核苷酸序列与B7抗原重链的氨基酸序列进行比较,发现有两个氨基酸差异。此外,与几个HLA和H - 2基因的编码区和非翻译区序列进行比较表明,I类组织相容性分子由四个可变区段组成,中间间隔三个同源区域。对DNA多态性的分析表明,在可变区段中,大多数核苷酸替换是有义的,而在同源区域中,大多数替换是无义的。对氨基酸替换性质的进一步分析表明,除分子的跨膜部分外,可变区段和同源区域中均以非保守替换/变化为主。蛋白质水平和密码子水平的选择都对I类组织相容性分子中发现的突变模式有影响。

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