IB生物 分子生物学 中心法则 基因表达 | IB Biology Molecular Biology Central Dogma Gene Expression

IB生物 分子生物学 中心法则 基因表达

IB Biology Topic 2 (Molecular Biology) is one of the heaviest content carriers in the Core syllabus. From DNA structure to protein synthesis, it bridges chemistry and genetics with a level of mechanistic detail that can overwhelm even strong students. 对IB考生来说，分子生物学不仅需要记忆大量术语(核酸、酶、聚合酶、引物、核糖体亚基)，更需要理解各个过程之间的逻辑关系。 **The Central Dogma states: DNA makes RNA makes protein.** But IB asks you to go far deeper: compare replication in prokaryotes and eukaryotes, explain transcription initiation, describe translation elongation, and connect it all through gene expression. Topic 2 appears in Paper 1, Paper 2 (data-based questions), and Paper 3 (Section A). HL students must additionally master Topic 7 (Nucleic Acids), which covers DNA structure at atomic resolution, Hershey-Chase and Rosalind Franklin's contributions, and the detailed enzymology of replication. 本文将四大核心对比串联成一条完整的逻辑链，帮你建立分子生物学的立体认知。

DNA vs RNA Structure: The Molecular Foundation DNA与RNA结构对比

At the heart of molecular biology lies the distinction between DNA and RNA. Both are nucleic acids composed of nucleotide monomers, but their structures define their functions. DNA是双链(double-stranded)的反平行双螺旋，脱氧核糖(deoxyribose)缺少2'位羟基使得DNA化学性质更稳定，适合长期储存遗传信息。RNA通常是单链(single-stranded)，核糖(ribose)的2'羟基使其更活泼但更易水解。In DNA, thymine (T) pairs with adenine (A); in RNA, uracil (U) replaces thymine. The absence of the methyl group on uracil is believed to be an evolutionary adaptation: cytosine can spontaneously deaminate to uracil, and if uracil were a normal DNA base, repair enzymes could not distinguish legitimate U from deaminated C. This is why DNA uses T instead of U: a key insight for IB extended-response questions.

DNA Replication: Prokaryotic vs Eukaryotic 原核与真核DNA复制对比

DNA复制是半保留复制(Semi-conservative replication)，每条子链包含一条母链和一条新链。This was elegantly demonstrated by the Meselson-Stahl experiment using N-15 and N-14 isotopes: after one generation in N-14, all DNA showed intermediate density, ruling out conservative replication. After two generations, half was intermediate and half was light, ruling out dispersive replication and confirming semi-conservative. IB经常要求你用Meselson-Stahl的实验结果来解释DNA复制机制 ： 记住：一代后全部居中(排除全保留)，两代后一半居中一半轻(排除分散保留)。 **Prokaryotic replication** (e.g., E. coli) occurs in the cytoplasm from a single origin of replication (oriC). DNA gyrase relieves supercoiling ahead of the replication fork. Helicase unwinds the double helix, and single-stranded binding proteins (SSBs) prevent re-annealing. DNA primase synthesizes RNA primers, and DNA polymerase III extends the new strand in the 5' to 3' direction. 因为DNA双链是反平行的，前导链(leading strand)可以连续合成，而滞后链(lagging strand)则以Okazaki片段(Okazaki fragments)的形式不连续合成。DNA polymerase I removes RNA primers and replaces them with DNA, and DNA ligase seals the nicks. **Eukaryotic replication** involves multiple origins of replication on each chromosome, allowing faster duplication of much larger genomes. 真核生物的DNA不是裸露的，而是缠绕在组蛋白(histone)上形成核小体(nucleosome)。复制叉前方需要拆卸核小体，复制后方需要重新组装 ： 这增加了复杂性。Eukaryotes also use multiple types of DNA polymerases (alpha, delta, epsilon), and telomerase adds repetitive sequences to the ends of linear chromosomes to solve the "end-replication problem" absent in circular prokaryotic chromosomes. **Key comparison summary:** - Origin: prokaryotes have 1 (oriC), eukaryotes have many - Location: prokaryotic cytoplasm, eukaryotic nucleus - DNA polymerase: prokaryotes use Pol III (main), eukaryotes use Pol alpha/delta/epsilon - Chromosome shape: prokaryotic circular, eukaryotic linear with telomeres - Rate: prokaryotic ~1000 bp/s, eukaryotic ~50 bp/s (slower due to chromatin)

Transcription: Prokaryotic vs Eukaryotic 原核与真核转录对比

转录(Transcription)是DNA模板链合成mRNA的过程，由RNA polymerase催化。Both use the template (antisense) strand in the 3' to 5' direction, synthesizing mRNA 5' to 3'. 但原核和真核生物的转录机制差异巨大。 **Prokaryotic transcription** is simpler: RNA polymerase holoenzyme (core enzyme + sigma factor) recognises promoter sequences at -10 (Pribnow box, TATAAT) and -35 (TTGACA). Sigma factor dissociates after initiation. mRNA is synthesised as a single continuous strand, and because prokaryotes lack a nucleus, translation can begin while transcription is still in progress ： a phenomenon called coupled transcription-translation. 原核生物的mRNA不需要加工：没有5' cap，没有poly-A tail，基因是连续的(无内含子)。 **Eukaryotic transcription** involves three different RNA polymerases: Pol I (rRNA), Pol II (mRNA), and Pol III (tRNA, 5S rRNA). 真核生物的启动子区域包含TATA box(约在-25位置)和多个转录因子结合位点。Transcription factors (TFIID, TFIIB, etc.) assemble at the promoter before RNA Pol II can bind ： this pre-initiation complex is a multi-step assembly absent in prokaryotes. After transcription, eukaryotic pre-mRNA undergoes extensive processing: 5' capping (7-methylguanosine), splicing (removal of introns by spliceosomes), and 3' polyadenylation (poly-A tail). Only after processing does mature mRNA exit the nucleus for translation. **Key comparison summary:** - RNA polymerase: prokaryotes have 1 type (with sigma factor), eukaryotes have 3 types (Pol I/II/III) - Promoter: prokaryotic -10/-35, eukaryotic TATA box with multiple transcription factors - Post-transcriptional modification: absent in prokaryotes, 5' cap + splicing + poly-A tail in eukaryotes - Coupled transcription-translation: occurs in prokaryotes, separated by nuclear membrane in eukaryotes - Gene structure: prokaryotic genes are continuous, eukaryotic genes contain introns and exons

Translation: Prokaryotic vs Eukaryotic 原核与真核翻译对比

翻译(Translation)是在核糖体上将mRNA的密码子(codon)转化为氨基酸链的过程。Both use the genetic code ： degenerate (multiple codons for one amino acid) and universal across all life. 核糖体由大亚基和小亚基组成：prokaryotes have 70S ribosomes (50S + 30S), while eukaryotes have 80S ribosomes (60S + 40S). The S (Svedberg) unit measures sedimentation rate during ultracentrifugation ： it is NOT additive (50S + 30S does not equal 80S because the combined shape differs from the sum of parts). 这是IB常考的概念题。 **Initiation:** 原核生物中，小亚基通过Shine-Dalgarno序列(位于mRNA起始密码子AUG上游约8个碱基)与16S rRNA的互补配对来识别起始位置。The initiator tRNA carries N-formylmethionine (fMet). In eukaryotes, the small subunit scans from the 5' cap until it finds the first AUG (Kozak sequence context), and the initiator tRNA carries methionine (not formylated). **Elongation:** 肽键形成的过程在两种生物中高度保守。The ribosome has three sites: A (aminoacyl), P (peptidyl), and E (exit). A charged tRNA enters the A site, a peptide bond forms between the amino acid in the P site and the incoming amino acid (catalysed by peptidyl transferase, which is rRNA ： a ribozyme!), the ribosome translocates one codon downstream (requiring EF-G/GTP in prokaryotes, eEF2/GTP in eukaryotes), and the uncharged tRNA exits through the E site. **Termination:** When a stop codon (UAA, UAG, UGA) enters the A site, release factors (RF1/RF2/RF3 in prokaryotes, eRF1/eRF3 in eukaryotes) trigger hydrolysis of the polypeptide from the tRNA, and the ribosomal subunits dissociate. **Key comparison summary:** - Ribosome: 70S (prokaryotic) vs 80S (eukaryotic) - Initiation: Shine-Dalgarno sequence vs 5' cap scanning + Kozak sequence - Initiator tRNA: fMet (prokaryotic) vs Met (eukaryotic) - Coupling: translation can couple with transcription in prokaryotes, not in eukaryotes - Antibiotic targeting: many antibiotics (tetracycline, streptomycin, chloramphenicol) target prokaryotic 70S ribosomes without affecting eukaryotic 80S ribosomes

Compare: PCR vs DNA Replication in vivo PCR与体内DNA复制的对比

PCR(Polymerase Chain Reaction，聚合酶链式反应)是一种体外(in vitro)扩增特定DNA片段的技术，与体内(in vivo)的DNA复制有诸多相似之处，却也有着根本差异。Understanding this comparison is essential for IB Paper 2 data-based questions. **Similarities:** Both processes synthesise new DNA in the 5' to 3' direction. Both require a template DNA strand. Both use primers to initiate synthesis. Both require a polymerase enzyme. 两者都遵循碱基互补配对原则(A-T, C-G)。 **Differences in detail:** PCR uses Taq polymerase (from Thermus aquaticus, a thermophilic bacterium) because the process cycles through 95°C (denaturation). 体内复制用的是DNA polymerase III(原核)或多种聚合酶(真核)，这些酶在高温下会变性。PCR primers are synthetic DNA oligonucleotides (18-25 bases), designed to flank the target sequence ： no primase needed. In vivo replication uses RNA primers synthesised by primase. PCR occurs in three temperature cycles: denaturation (95°C, separates double-stranded DNA), annealing (50-65°C, primers bind to complementary sequences), and extension (72°C, Taq polymerase synthesises new strands). 体内复制是在37°C恒温下进行的连续过程。PCR amplifies a specific target sequence exponentially (2^n after n cycles), while in vivo replication duplicates the entire genome once per cell division. PCR requires a thermal cycler, dNTPs, target DNA, primers, Taq polymerase, and buffer. 体内复制需要一整套复杂的酶系统(解旋酶、DNA旋转酶、SSB蛋白、引物酶、DNA聚合酶I/III、连接酶)。A key practical application: PCR is used in DNA profiling (forensics, paternity testing), where STR loci are amplified and separated by gel electrophoresis. The number of STR repeats at each locus varies between individuals, creating a unique DNA fingerprint. IB Paper 2 frequently presents gel electrophoresis images and asks you to identify which suspect's DNA matches the crime scene sample ： remember: smaller fragments migrate further toward the positive electrode. **Key comparison summary:** - Temperature: PCR cycles 50-95°C, in vivo constant ~37°C - Polymerase: Taq polymerase (PCR) vs DNA Pol III (in vivo) - Primers: synthetic DNA oligos (PCR) vs RNA primers from primase (in vivo) - Product: specific short sequence (PCR) vs entire genome (in vivo) - Enzyme complexity: single polymerase (PCR) vs multi-enzyme replisome (in vivo)

Gene Expression and Regulation 基因表达与调控

Gene expression is the process by which information from a gene is used to synthesise a functional gene product (usually a protein, sometimes functional RNA). 基因表达调控决定了哪些基因在何时、何地、以何种水平表达 ： 这是细胞分化和生物体发育的基础。 In prokaryotes, gene regulation often occurs at the transcriptional level through operons. The lac operon in E. coli is the classic example: when lactose is present and glucose is absent, the repressor protein is inactivated by allolactose, and CAP (catabolite activator protein) bound to cAMP activates transcription. 原核生物的基因表达调控比较直接：转录因子结合 → mRNA合成 → 翻译 → 蛋白质。由于原核生物没有细胞核，调控主要在转录水平。 Eukaryotic gene regulation is vastly more complex, occurring at multiple levels: chromatin remodelling (histone acetylation/deacetylation, methylation), transcriptional regulation (enhancers, silencers, transcription factors), post-transcriptional regulation (alternative splicing, mRNA stability, microRNA interference), translational regulation, and post-translational modification (phosphorylation, ubiquitination, proteolytic cleavage). Enhancers can be located thousands of base pairs away from the promoter ： DNA looping brings them into physical proximity. 真核生物的调控层次多得惊人：同一个基因可以通过可变剪接产生多种蛋白质亚型，mRNA的半衰期从几分钟到数小时不等，microRNA可以在翻译前结合mRNA的3' UTR区，诱导降解或阻断翻译。Promoter-proximal elements like the CAAT box and GC box further fine-tune transcription rates. DNA methylation (adding methyl groups to cytosine bases in CpG islands) typically silences gene expression. Histone acetylation (adding acetyl groups to lysine residues on histone tails) generally activates gene expression by loosening chromatin structure. The pattern of these modifications is called the "histone code," and it determines whether chromatin is in the open euchromatin state (transcriptionally active) or the compact heterochromatin state (transcriptionally silent). 这些表观遗传修饰(epigenetic modifications)是可逆的，不改变DNA序列本身，但影响基因的可及性：这是IB HL的重要内容。For example, X-inactivation in female mammals involves heavy DNA methylation and histone deacetylation of one X chromosome, forming a Barr body.

Exam Tips for IB Molecular Biology IB分子生物学考试技巧

Paper 1 (multiple choice) often tests the subtle distinctions: the difference between transcription and translation in prokaryotes vs eukaryotes, the role of specific enzymes, and the directionality (5' to 3') of all polymerisation reactions. Remember: ALL DNA and RNA polymerases synthesise 5' to 3', using a 3' to 5' template. 这是IB最爱考的方向性问题。 Paper 2 data-based questions frequently ask you to interpret gel electrophoresis results (used in DNA profiling), PCR amplification curves, or Meselson-Stahl density gradient data. Practice identifying the number of bands and their positions relative to N-14 and N-15 standards. 凝胶电泳中，小片段迁移得更快(更接近正极)，大片段迁移得慢。DNA profiling使用STR(短串联重复序列)，不同的等位基因产生不同长度的片段。 The "compare" command word (compare and contrast) appears regularly. Structure your answer: one similarity, then one difference, each with specific molecular detail. 不要只写PCR和体内复制都用引物 ： 要补充"但PCR用DNA引物而体内复制用RNA引物"才能拿满分。 Common pitfalls: confusing transcription and translation directionality, mixing up the lac operon's on-off logic (lactose present = operon ON, but ONLY when glucose is absent), forgetting that post-transcriptional modification only occurs in eukaryotes, and using "energy" loosely instead of naming ATP or GTP specifically. When answering "outline the process of translation," IB expects you to name the A, P, and E sites, describe translocation requiring GTP, and specify that peptidyl transferase is a ribozyme. 在IB生物中，精确的分子机制术语是得分关键：写解旋酶(helicase)而不是"把双链分开"，写肽基转移酶(peptidyl transferase)而不是"形成肽键"。For Paper 2 Section B extended-response (8-mark) questions on molecular biology, aim for 10-12 distinct marking points. A strong answer on DNA replication should cover: semi-conservative nature, Meselson-Stahl evidence, role of helicase/gyrase/SSBs/primase/Pol III/Pol I/ligase, leading vs lagging strand, Okazaki fragments, and 5' to 3' directionality of synthesis.

Key Bilingual Terms 关键双语术语

Semi-conservative replication 半保留复制 | Helicase 解旋酶 | DNA gyrase DNA旋转酶 | SSB proteins 单链结合蛋白 | Okazaki fragments 冈崎片段 | Leading strand 前导链 | Lagging strand 滞后链 | Promoter 启动子 | Sigma factor σ因子 | TATA box TATA框 | Spliceosome 剪接体 | 5' cap 5'帽结构 | Poly-A tail 多聚腺苷酸尾 | Shine-Dalgarno sequence SD序列 | Peptidyl transferase 肽基转移酶 | Ribozyme 核酶 | Taq polymerase Taq聚合酶 | PCR 聚合酶链式反应 | Thermal cycler 热循环仪 | STR 短串联重复序列 | Gel electrophoresis 凝胶电泳 | Lac operon 乳糖操纵子 | Epigenetics 表观遗传学 | Histone acetylation 组蛋白乙酰化 | DNA methylation DNA甲基化

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