📚 Gene Mutations | 基因突变
Gene mutations are permanent changes in the nucleotide sequence of DNA. They can occur spontaneously during DNA replication or be induced by mutagens. Although many mutations are neutral or harmful, some provide genetic variation essential for evolution. In A-Level Biology, understanding the types, causes and consequences of mutations is fundamental to genetics, protein synthesis and disease.
基因突变是DNA核苷酸序列的永久性改变，可在DNA复制时自然发生或由诱变剂诱导。尽管许多突变是中性的或有害的，但部分突变为进化提供了必需的遗传变异。在A-Level生物中，理解突变的类型、原因和后果是遗传学、蛋白质合成与疾病部分的基础。
1. What Are Gene Mutations? | 什么是基因突变？
A gene mutation is a change in the base sequence of DNA. It may involve a single nucleotide or a larger segment of a chromosome. These alterations can affect the structure and function of proteins, sometimes leading to genetic disorders.
基因突变是指DNA碱基序列的改变，可能涉及单个核苷酸或一段染色体片段。这些变化可影响蛋白质的结构与功能，有时会导致遗传病。
Mutations are distinct from chromosome mutations, which involve changes in the number or structure of whole chromosomes. In A-Level exams, ‘gene mutation’ refers specifically to changes within a gene at the nucleotide level.
突变不同于染色体突变，后者涉及整个染色体数目或结构的改变。在A-Level考试中，“基因突变”特指基因内部核苷酸水平的变化。
2. Substitution Mutations | 碱基替换突变
A substitution mutation occurs when one nucleotide base is replaced by another. For example, in a DNA sequence, an ‘A’ might be replaced by a ‘G’. This changes one codon in the mRNA, potentially altering a single amino acid in the polypeptide.
碱基替换突变是指一个核苷酸碱基被另一个碱基取代。例如，DNA序列中的“A”可能被“G”替换。这会改变mRNA中的一个密码子，可能改变多肽链中的一个氨基酸。
Substitutions are also called point mutations. They are often less damaging than insertions or deletions because they do not cause a frameshift. However, their effect depends on the role of the changed amino acid in protein folding and function.
替换突变也称为点突变。它们通常比插入或缺失突变的危害小，因为不会引起移码。但其影响取决于被改变的氨基酸在蛋白质折叠和功能中的作用。
3. Frameshift Mutations: Insertion and Deletion | 移码突变：插入与缺失
Insertion or deletion of a number of nucleotides that is not a multiple of three leads to a frameshift mutation. The reading frame of the genetic code shifts, altering every codon from the point of mutation onward. This often produces a completely different amino acid sequence and a premature stop codon.
插入或缺失的核苷酸数目不是3的倍数时，会导致移码突变。遗传密码的阅读框发生改变，从突变点开始后的每一个密码子都发生变化。这通常产生完全不同的氨基酸序列和提前的终止密码子。
For example, consider the DNA sequence ATG GCC TAC. If an extra ‘A’ is inserted after ATG, it becomes ATG AGC CTA C. The codons are now ATG, AGC, CTA, etc., entirely different from the original. The resulting polypeptide is non-functional in most cases.
例如，考虑DNA序列ATG GCC TAC。如果在ATG后插入一个多余的“A”，序列变为ATG AGC CTA C。现在的密码子是ATG、AGC、CTA等，与原来完全不同。在大多数情况下产生的多肽没有功能。
If exactly three nucleotides are inserted or deleted, the reading frame is restored, and only one amino acid is gained or lost. This may have a milder effect.
如果恰好插入或缺失三个核苷酸，阅读框得以恢复，只增加或丢失一个氨基酸，影响可能较轻微。
4. Effects of Mutations on Protein Function | 突变对蛋白质功能的影响
Mutations can be classified by their effect on the polypeptide: silent, missense or nonsense. A silent mutation has no effect on the amino acid sequence because the genetic code is degenerate; the new codon codes for the same amino acid.
突变可根据对多肽的影响分为：沉默突变、错义突变或无义突变。沉默突变不影响氨基酸序列，因为遗传密码具有简并性，新密码子仍编码相同氨基酸。
A missense mutation results in a different amino acid being incorporated. The protein may still function, especially if the new amino acid has similar properties to the original. Sickle cell anaemia is caused by a missense mutation in the haemoglobin gene.
错义突变导致嵌入不同的氨基酸。蛋白质可能仍具功能，尤其是当新氨基酸性质与原氨基酸相似时。镰状细胞贫血由血红蛋白基因中的一个错义突变引起。
A nonsense mutation changes an amino acid codon into a stop codon. This truncates the polypeptide, almost always resulting in a non-functional protein. Nonsense mutations are often associated with severe genetic diseases such as cystic fibrosis.
无义突变将一个氨基酸密码子变为终止密码子。这使多肽链提前终止，几乎总会产生无功能的蛋白质。无义突变通常与严重的遗传病如囊性纤维化有关。
5. Spontaneous Mutations | 自发突变
Spontaneous mutations arise without external influence. They occur due to errors in DNA replication, such as base mismatches that escape proofreading by DNA polymerase. Tautomeric shifts in nitrogenous bases can cause incorrect base pairing.
自发突变在没有外界影响下发生。它们由DNA复制中的错误引起，例如逃脱DNA聚合酶校对作用的碱基错配。含氮碱基的互变异构位移可导致错误配对。
Depurination (loss of a purine base) and deamination (e.g., cytosine to uracil) are chemical reactions that happen naturally in cells and can lead to permanent mutations if not repaired.
脱嘌呤（失去嘌呤碱基）和脱氨基（如胞嘧啶变为尿嘧啶）是细胞内自然发生的化学反应，如果不被修复，可导致永久性突变。
The rate of spontaneous mutation is very low, about one error per 10⁹ base pairs replicated, due to efficient proofreading and DNA repair systems.
由于高效的校对和DNA修复系统，自发突变率很低，大约每复制10⁹个碱基对才出现一个错误。
6. Induced Mutations and Mutagens | 诱导突变与诱变剂
Induced mutations are caused by mutagens – environmental agents that significantly increase the mutation rate. Mutagens can be physical or chemical. Ionising radiation such as X‑rays and gamma rays breaks DNA strands, causing deletions or rearrangements.
诱导突变由诱变剂引起，诱变剂是显著提高突变率的环境因素。诱变剂可为物理或化学因素。电离辐射如X射线和γ射线会断裂DNA链，导致缺失或重排。
Ultraviolet light induces the formation of thymine dimers, where adjacent thymine bases on the same strand bond together. This distorts the DNA helix and blocks replication and transcription.
紫外线诱导胸腺嘧啶二聚体的形成，即同一条链上相邻的胸腺嘧啶交联在一起。这扭曲了DNA螺旋，阻碍复制和转录。
Chemical mutagens include base analogs (e.g., 5‑bromouracil) that mimic normal bases but pair incorrectly, and intercalating agents that insert between bases and cause frameshifts during replication.
化学诱变剂包括碱基类似物（如5-溴尿嘧啶），它们模拟正常碱基却错误配对，以及嵌入剂，它们插入碱基之间并在复制时引起移码。
7. DNA Repair Mechanisms | DNA修复机制
Cells possess several mechanisms to repair mutated or damaged DNA, protecting the genome from permanent change. Proofreading by DNA polymerase III (in prokaryotes) immediately corrects most replication errors.
细胞拥有多种机制来修复突变或受损的DNA，保护基因组免于永久改变。DNA聚合酶III（在原核生物中）的校对功能能立即纠正大多数复制错误。
Mismatch repair enzymes detect and excise incorrectly paired bases after replication. Nucleotide excision repair removes bulky lesions such as thymine dimers by cutting out a short single‑stranded segment and resynthesising it using the complementary strand as a template.
错配修复酶在复制后识别并切除错配碱基。核苷酸切除修复通过切除一段短的单链片段，并以互补链为模板重新合成，来去除胸腺嘧啶二聚体等大体积损伤。
Base excision repair corrects small, non‑helix‑distorting base lesions like deaminated cytosine. A specific glycosylase removes the damaged base, then the backbone is cleaved, and the gap filled.
碱基切除修复能纠正小的、不扭曲螺旋的碱基损伤，如脱氨基胞嘧啶。特定的糖苷酶移除受损碱基，接着切断主链，填补缺口。
If repair fails, mutated cells may undergo apoptosis, preventing the propagation of potentially harmful mutations.
如果修复失败，突变细胞可能发生凋亡，阻止潜在有害突变的传播。
8. Sickle Cell Anaemia: A Case Study | 镰状细胞贫血：一个实例分析
Sickle cell anaemia is caused by a single substitution mutation in the gene for the β‑globin chain of haemoglobin. The DNA triplet GAG is changed to GTG, which in mRNA becomes GUG instead of GAG. This replaces glutamic acid with valine at position 6 of the polypeptide.
镰状细胞贫血由编码血红蛋白β-珠蛋白链的基因发生单个替换突变引起。DNA三联体GAG变为GTG，mRNA上即由GAG变为GUG，导致多肽链第6位的谷氨酸被缬氨酸取代。
| Description / 描述 | Normal / 正常 | Sickle cell / 镰状细胞 |
|---|---|---|
| DNA triplet | GAG | GTG |
| mRNA codon | GAG | GUG |
| Amino acid | Glutamic acid / 谷氨酸 | Valine / 缬氨酸 |
| Haemoglobin | HbA (soluble) / 可溶 | HbS (insoluble when deoxygenated) / 缺氧时不溶 |
| Red blood cell shape | Biconcave disc / 双凹圆盘状 | Sickle‑shaped / 镰刀形 |
The valine residue is non‑polar, causing haemoglobin molecules to stick together under low oxygen conditions, forming rigid fibres that distort red blood cells into a sickle shape. These sickled cells block capillaries, causing pain and organ damage.
缬氨酸残基是非极性的，在低氧条件下导致血红蛋白分子相互黏附，形成刚性纤维，使红细胞扭曲成镰刀形。这些镰状细胞阻塞毛细血管，引起疼痛和器官损伤。
9. Mutations and Evolution | 突变与进化
Although many mutations are harmful or neutral, they are the ultimate source of genetic variation upon which natural selection acts. In asexual reproduction, mutations are the primary source of variation, whereas in sexually reproducing organisms, meiosis and fertilisation create new allele combinations.
尽管许多突变有害或中性，但它们是自然选择作用于其上的遗传变异的最终来源。在无性生殖中，突变是变异的主要来源；而在有性生殖的生物中，减数分裂和受精创造新的等位基因组合。
A beneficial mutation increases an organism’s fitness, making it more likely to survive and reproduce. For example, mutations in the CCR5 gene confer resistance to HIV infection. Over generations, favourable alleles increase in frequency in the population.
有利突变提高生物的适合度，使其更有可能生存和繁殖。例如，CCR5基因的突变赋予对HIV感染的抵抗力。经过数代，有利等位基因在种群中的频率上升。
The sickle cell allele, though deleterious in homozygotes, provides a heterozygote advantage in regions where malaria is endemic, as heterozygotes are more resistant to the malaria parasite. This maintains the allele in the population.
镰状细胞等位基因虽然在纯合子中有害，但在疟疾流行地区为杂合子提供了优势，因为杂合子对疟原虫的抵抗力更强。这使该等位基因在种群中得以维持。
10. Exam Tips on Gene Mutations | 基因突变备考要点
When answering A‑Level questions on mutations, always be precise about the level of change: base substitution, insertion or deletion, and whether a frameshift occurs. Use correct terminology such as silent, missense and nonsense, and support with specific examples like sickle cell anaemia.
回答A‑Level关于突变的题目时，务必精确描述变化层次：碱基替换、插入或缺失，以及是否发生移码。使用正确术语，如沉默、错义、无义，并用镰状细胞贫血等具体实例佐证。
Many mark schemes expect you to link a mutation to the change in the primary structure of the protein and then to the consequence for the final shape and function. Always mention how changes in hydrogen bonds, ionic bonds and disulfide bridges alter the tertiary structure.
许多评分标准期望你将突变与蛋白质一级结构的变化联系起来，再说明对最终形状和功能的影响。务必提及氢键、离子键和二硫键的改变如何影响三级结构。
Be able to compare the severity of substitution vs frameshift mutations. A substitution may be tolerated, while a frameshift often destroys protein function completely. Also discuss repair mechanisms and the role of mutations in generating genetic diversity.
要能够比较置换与移码突变的严重性。置换突变可能被耐受，而移码突变常彻底破坏蛋白质功能。同时讨论修复机制以及突变在产生遗传多样性中的作用。
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