医学分子生物学_第二章 基因

带负电荷的核酸在电场中向正极泳动，泳动速 率与其分子量的对数近似负线性关系
2000 bp 1500 bp 1000 bp 700 bp
500 bp 400 bp 300 bp 200 bp
100 bp
50 bp
Size of DNA fragment
M
1
2
3
4
5 Cathode(-)
900bp 800bp 700bp 600bp 500bp
– Example: methylation （甲基化）of the N-6 position of adenine and the 4-amino group, and the 5-position of cytocine, phage DNAs; modifications of RNA.
核酸的物理化学性质
Effect of acid(酸效应 酸效应) 酸效应 • Highly acidic conditions may hydrolyze nucleic acids to their components: bases, sugar and phosphate. Moderate acid causes the hydrolysis of the purine base glycosylic bonds （糖苷键） to yield 糖苷键） apurinic acid（脱嘌啉核苷酸）. （脱嘌啉核苷酸） • More complex chemistry has been developed to remove particular bases, and is the basis of chemical DNA sequencing.
基因的概念及其含义的演变
参见“医学分子生物学---第一章 绪论” 相关学习网站： (NHGRI官方网站)
Eukaryotic Central Dogma
启动子
外显子
内含子 转录 RNA剪接 剪接 下游
上游
RNA初始转录本 初始转录本
非翻译序列 翻译 蛋白
Viscosity(黏滞性 黏滞性) 黏滞性
• DNA solutions have high viscosity（粘滞 性）. Long DNA molecules are susceptible to cleavage by shearing（剪 切）(or by sonication（超声）in solution – this process can be used to generate DNA of a specific average length.
Table 1.1 Forms of DNA
Form Pitch(nm) Residues per turn Inclination of base pair from horizontal
A B C D Z
RNA-DNA hybrid
0. 26 0.34 0.33 0.30 0.45 0.28
Effect of alkali(碱效应 碱效应) 碱效应 • High pH denatures DNA and RNA by altering the tautomeric （互变异构） 互变异构） state of the bases and disrupting specific hydrogen bonding. • RNA is also susceptible to hydrolysis at high ramolecular cleavage of the phosphodiester backbone.
11 10 9.33 8.5 12 11
20º 0º
7º 20º
RNA secondary structure
• Most RNA molecules occur as a single strand （单链）, which may be folded into a complex conformation, involving local regions of intramolecular base pairing（分子内碱基配 对） and other hydrogen bonding interactions.
医学分子生物学
第二章 基因
结构与功能
易光辉 南华大学医学院分子生物学研究中心 2009-11
Genes:
Structure and Function
by Prof. Guanghui Yi
ghyi6108@ 13974778329 Institute of Cardiovascular Disease Research Center for Molecular Biology Medical College, University of South China 2009-11
Stability of nucleic acids(核酸的稳定性 ) 核酸的稳定性
• Although it might seem obvious that DNA double strands and RNA structures are stabilized by hydrogen bonding, this is not the case. • H-bonds determine the specificity of the base pairing, but the stability of a nucleic acid helix is the result of hydrophobic（疏水） （疏水） and dipole-dipole interactions（双极 双极相 （双极-双极相 堆叠） 互作用） 互作用） between the stacked （堆叠）base pairs.
Examples: 5’-ATAAGCTC-3’ (DNA ), 5’-AUAGCUUGA-3’ (RNA).
DNA double helix • Two separate and antiparallel chains （反向平行）of DNA are wound around each other in a right-handed helical (coiled) path, with the sugar-phosphate backbones on the outside and the bases, paired by hydrogen bonding and stacked on each other, on the inside. Adenine pairs with thymine; guanine pairs with cytosine. The two chains are complemently（互 补）; one specifies the sequence of the other.
成熟RNA 成熟
• Gene: A DNA segment containing biological information and hence coding for an RNA and/or polypeptide molecule. • 基因是含有生物信息的 基因是含有生物信息的DNA片段，根据 片段， 片段 这些生物信息可以编码具有生物功能的 产物，包括RNA和多肽链。 和多肽链。 产物，包括 和多肽链
Chemical and Physical Properties of Nucleic Acids
核酸的物理化学性质
• • • • • Stability of nucleic acids（核酸稳定性） Effect of acid（酸效应） acid Effect of alkali（碱效应） Chemical denaturation（化学变性） Viscosity（粘滞性）
Nucleotides In ribonucleotides(核苷酸）(CMP, CTP, ATP, GTP, UTP), the 2’-position is hydroxyl group. If the sugar is deoxyribose, then compounds are deoxynucleotides（脱氧核苷酸）(dATP, dGTP, dCTP, dTTP; dNTP). Base+sugar+phosphate=nucleotide.
基因的分子本质 Genes: Molecular Nature
碱基配对
T A
A:T
G:C
C G
双链 DNA的结构
• • • • 右手方向双股螺旋 反向平行 共同轴心 大沟和小沟
Bases In DNA, there are four heterocyclic bases: adenine(A)（腺嘌啉） and quinine(G)（鸟嘌啉） are purines; cytosine(C)（胞嘧啶） and thymine(T) （胸腺嘧啶） are pyrimidines. In RNA, thymine is replaced by the structurally very similar pyrimidine, uracil(U)（尿嘧啶）.
Phosphodiester bonds Between the 5’-position of one sugar and the 3’-position of the next, forming a 3’, 5’phosphodiester bond. Nucleic acids are highly charged polymers with a negative charge（负 电荷） on each phosphate.
Chemical denaturation(化学变性 化学变性) 化学变性
• Some chemicals, such as urea（尿素） （尿素） and formamide（甲酰胺）, can （甲酰胺） denature DNA and RNA at neutral pH by disrupting the hydrophobic forces between the stacked（堆叠）bases. （堆叠）