【作者】 黄惠芳；

【导师】 纪志梁； 马飞；

【作者基本信息】 厦门大学 ， 生化与分子生物学， 2006， 硕士

【摘要】 遗传密码子(Genetic Codes)是连接基因和蛋白质的桥梁。通过研究密码子与互补密码子在疾病选择性剪接形成及物种进化中使用频率的差异,将有助于从新的角度来了解选择性剪接的进化及其导致人类疾病的可能分子机制。本文统计分析了118个人类疾病相关的选择性剪接基因编码区中2,903个单核苷酸替代的特征:在选择性剪接基因的单碱基替代中,最普通的替代类型依次是C|T (C/T或T/C) (31.97 %)和A|G (28.14 %)替换、G|T (13.65 %)和C|G (12.47 %), A|C和A|T替换是较少的,分别为7.44 %和6.34 %。转换(A|G和C|T)60.11 %大于颠换(A|C、G|T、A|T和C|G)39.89 %。密码子第一、第二和第三位碱基替代的等次分别为C > G > A > T、G > C > T > A和C > G >T > A,其比例分别为49.26 %、42.16 %和8.58 %。在对60种生物(13种真核生物,26种细菌,5种古细菌和16种病毒)基因组和60种细胞器(40种线粒体和20种叶绿体)基因组的密码子与互补密码子数据的分析中,显示密码子与互补密码子存在显著或极显著的相关性。对70个物种(5个古细菌,20个真核生物和45个细菌)基因组密码子与互补密码子的分析支持了上一步的结果,并发现密码子与互补密码子的使用相关系数和GC含量之间存在显著的相关性。基于密码子与互补密码子使用频率差异,我们构建了密码子与互补密码子使用的进化树;结果表明密码子与互补密码子使用的进化树可以反应物种的协同进化过程。更多还原

【Abstract】 Genetic code is the biological language in communication between DNA and protein. To reveal the role of different usage of genetic codons and their complementary codons in the evolution of disease-associated alternative splicing, 118 alternatively spliced human genes with 2,903 nucleotide substitutions were statistically analyzed. It is found that nucleotide tranitions has overall preponderance over nucleotide transversions (60.11 % versus 39.89 %). The propobility of substituation in the first, second and third base of codons are 49.26 %, 42.16 % and 8.58 %, respectively. Among tri-nucleotides (triplets) formed by the substitutions (denoted as N) and their immediate neighboring nucleotides (5’ to 3’), 1,866 (64.28 %) are of pyrimidine-N-purine or purine-N-purine types. Futher exon analysis of these disease-related genes found that single base substitutions are much denser within the first and last two exons than that of middle exons. 83.91 % of substitutions have occurred within exons that have a medium range (40 ~ 65 %) of GC content. Larger exons seem to have suffered fewer substitutions. Additional study of 44 cellular organisms, 16 viruses, 40 mitochondria and 20 chloroplasts indicates that there exist significant correlation between codons and corresponding complementary codons usage in species except virus. Moreover, phylogentic tree was generated based on this finding, which is comparable to traditional molecular evolution tree.更多还原