Spontaneousmutationsdifferfrom inducedmutations:Spontaneousmutationscanoccuratanypointofthecell cycleMovementoftransposons(mobilegeneticelements)Mutationrate=~10-4to10-6mutations/gene/generationRatesvarybylineage,andmostspontaneouserrorsarerepaired
Spontaneous mutations differ from induced mutations: • Spontaneous mutations can occur at any point of the cell cycle. • Movement of transposons (mobile genetic elements) • Mutation rate = ~10-4 to 10-6 mutations/gene/generation • Rates vary by lineage, and most spontaneous errors are repaired
SpontaneouschemicalchangescancausemutationExample:Deamination:C→U.C→Ta)NH2HDeaminationCytosineUracilb)MethylNH2groupCH3CH3DeaminationH5-methylcytosine (5mC)Thymine(T)
Spontaneous chemical changes can cause mutation Example : Deamination: C U, C T
Induced mutationsRadiation (e.g., X-rays, UV)lonizing radiation breaks covalent bonds including those in DNA and is the leadingcauseofchromosomemutationsUV (254-260 nm) causes purines and pyrimidines to form abnormal dimer bondsandbulgesintheDNAstrandsThymineThymineThyminedimer
Induced mutations Radiation (e.g., X-rays, UV) Ionizing radiation breaks covalent bonds including those in DNA and is the leading cause of chromosome mutations. UV (254-260 nm) causes purines and pyrimidines to form abnormal dimer bonds and bulges in the DNA strands. Thymine dimers induced by UV light
Inducedmutations:chemicalmutagensBaseanalogsSimilartonormal bases,incorporatedinto DNAduringreplicationSome cause mis-pairing (e.g., 5-bromouracil)Base modifying agents,actatanystage of thecell cycle:Deaminating agentsHydroxylatingagentsAlkylatingagents
Induced mutations: chemical mutagens Base analogs • Similar to normal bases, incorporated into DNA during replication. • Some cause mis-pairing (e.g., 5-bromouracil). Base modifying agents, act at any stage of the cell cycle: • Deaminating agents • Hydroxylating agents • Alkylating agents
突变发生在基因的非编码区调节位点ACAGCGTGGT在非编码区的点突变GAGCGTGGT调节蛋白不能结合调节区和非编码区的DNA序列DNA水平：包括RNA聚合酶、特定转录因子的结合位点；RNA水平：包括核糖体结合位点，真核生物mRNA外显子交接区5'和3端拼接位点，以及调节mRNA进入细胞特定区域和组分的翻译调节和定位信号位点
突变发生在基因的非编码区 调节区和非编码区的DNA序列: DNA水平: 包括RNA聚合酶、特定转录因子的结合位点； RNA水平：包括核糖体结合位点，真核生物mRNA 外显子交接区5′和3′端拼接位点, 以及调节mRNA进入细胞特定区域和组分的翻译调节和定位信号位点