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乙型肝炎病毒X蛋白(hepatitis B virus X protein,HBx)全长154个氨基酸,与肝癌发生密切相关。为确定HBx的优势氨基酸序列和热点突变位点,在GenBank中下载所有HBx的氨基酸序列13 950条,剔除插入突变、缺失突变和起始密码子非甲硫氨酸的序列,最后保留7 126条。通过分析这7 126条序列,计算出HBx每个位点的氨基酸分布情况,出现频率最高的氨基酸为该位点的优势氨基酸,其他氨基酸为突变氨基酸。154个位点的优势氨基酸组成HBx优势氨基酸序列。突变率>10.0%的热点突变位点有32个。其中第36、42、44、87、88和127位氨基酸有4种(突变率>1.0%)以上突变形式,具有较高的多态性。与肝癌密切相关的K130M/V131I双突变率为34.7%。通过7 126条HBx序列与优势序列的同源性比较,随机选出其中50条序列(2条与优势序列同源性<75%,48条同源性为76%~99%),与23条参考序列及优势序列共同构建系统发生树。结果显示,HBx优势氨基酸序列属于基因型C,这与基因型C为全球主要流行型一致。本研究首次系统性分析了GenBank中HBx的优势序列,确定了32个HBx热点突变位点和6个多态性较高的位点,为基于HBx突变的基础和应用研究奠定了基础。
Hepatitis B virus X protein (HBx) is 154 amino acids in length, which is closely related to the occurrence of liver cancer. To identify the dominant and hot spot mutations of HBx, 13 950 amino acid sequences of all HBx were downloaded from GenBank and the sequences of insertional mutations, deletion mutations and start codon non-methionine were deleted and finally 7 126 . By analyzing these 7 126 sequences, the distribution of amino acids at each position of HBx was calculated. The amino acids with the highest frequency of occurrence were the dominant amino acids at this site, and the other amino acids were mutant amino acids. The dominant amino acid at 154 loci constitutes the dominant amino acid sequence of HBx. There are 32 hotspot mutation sites with the mutation rate> 10.0%. Among them, 36 (superscript th), 42 (superscript th), 44 (superscript th), 84 (superscript th), 87 th, 81 (superscript th), 127 (superscript th) and 127 (superscript th) amino acids have more mutation (> 1.0%). The double mutation rate of K130M / V131I closely related to liver cancer was 34.7%. By comparing the homology of 7 126 HBx sequences with the dominant sequences, 50 sequences were randomly selected (2 with homology <75%, 48 with homology 76% -99%) and 23 The reference sequence and the dominant sequence construct the phylogenetic tree. The results showed that the dominant amino acid sequence of HBx belongs to genotype C, which is consistent with genotype C being the major epidemic in the world. This study, for the first time, systematically analyzed the dominant sequences of HBx in GenBank, identified 32 HBx hotspot mutation sites and 6 polymorphic sites, which laid the foundation for the basic and applied research on HBx mutation.