第三節(jié)分子生物學的中心法則thecentraldogmaofmolecularbiology

1、Chapter 10 Gene Mutation,Severe Acute Respiratory Syndrome (SARS),,H1N1 流感病毒,流感的啟示……,問題,1、為什么每一次大流行的流感病毒的類型都不一樣？2、為什么如此猖狂和恐怖的流感病毒不能像天花病毒一樣被“消滅”？為什么不能通過接種疫苗進行有效的預(yù)防？,血凝素（HA）,神經(jīng)氨酸酶（NA），,SARS的S蛋白質(zhì)和M蛋白質(zhì)的變異點位達到31個，這說明SARS

2、病毒具有極強的變異能力，這意味著研究SARS疫苗可能會同研究流感疫苗一樣困難重重……,1、What Are Mutations?,4、What Causes Mutations?,3、Consequences of Mutations,5、How to Detect the Gene Mutation?,2、 Features of Gene Mutantion,OUTLINE,Chapter 10 Gene Mutation

3、,1、What Are Mutations?,★ Any heritable change in the DNA（RNA） sequence of an organism is a mutation.★ Mutations can be divided into three main types1. Chromosome mutations（染色體突變）2. Genome mutations（基因組突變）3. gene

4、mutations（基因突變）Relatively small changes in DNA structure that occur within a particular gene,★ Gene mutation（基因突變）: changes in one or a few nucleotides.★ point mutation(點突變) are mutations of a single nucleotide.Includes

5、 the deletion, insertion, or substitution in a gene.（堿基的增加及缺失、堿基替換）,替換,增加及缺失,,A transition(轉(zhuǎn)換) is a change of a pyrimidine (C, T) to another pyrimidine or a purine (A, G) to another purineA transversion(顛換) is a change

6、 of a pyrimidine to a purine or vice versa,轉(zhuǎn)換和顛換的相互關(guān)系示意圖,,Mutations may also involve the addition or deletion of short sequences of DNA,,5’ AACGCTAGATC 3’3’ TTGCG ATCTAG 5’,5’ AACGCTC 3’3’ TTGCGAG 5’,,Deletion of fou

7、r base pairs,Addition of four base pairs,Mutations Due to Trinucleotide Repeats（dynamic mutation）,Mutations happen regularlyMutation rateForward & backward(or reverse) mutationMultiple orientations Beneficial &am

8、p; deleteriousMutation similarity between the related species,2、 Features of Gene Mutantion,Mutations happen regularly,Therefore, the mutation can be passed on to future generations,,The size of the patch will dep

9、end on the timing of the mutation,The earlier the mutation, the larger the patch,An individual who has somatic regions that are genotypically different from each other is called a genetic mosaic,Therefore, the mut

10、ation cannot be passed on to future generations,Mutation rate,The frequency with which a particular mutation appears in a population.,Forward & backward(or reverse) mutation(正突變&回復(fù)突變),A,,a,,forward,reverse,通常從一

11、個野生型基因變成突變性的頻率總是高于回復(fù)突變率，如何解釋？,一突變型回復(fù)成野生型，可能機制是什么？（預(yù)習基因重組）,,A,,a1,,a2,,a3,,,,,,,,,,Multiple orientations（多向性）,Beneficial & deleterious,,Harmful,Almost all mutations are neutral,beneficial,,Some terms,lethal mutation（

12、致死突變）: Mutation that eventually results in the death of an organism carrying the mutation.neutral mutation（中性突變）: A mutation that has no selective advantage or disadvantage.conditional mutation（條件突變）: A mutatio

13、n that is only expressed under certain environmental conditions.,Mutation similarity between the related species（突變的平行性）,,+,3、Consequences of Mutations,Mutations in the coding sequence of a structural gene (can hav

14、e various effects on the polypeptide),Mutations in Non-coding Sequences(affect gene expression),,,,,,,insert,3、Consequences of Mutations- coding sequence,3、Consequences of Mutations- coding sequence,☆Silent mutations (o

15、r silent) mutation（同義突變）: base substitutions that do not alter the amino acid sequence of the polypeptide. ☆ Missense mutations(錯義突變) are those base substitutions in which an amino acid change does occur. ☆ Nonsense

16、mutations （無義突變）: are those base substitutions that change a normal codon to a termination codon. ☆ Frameshift mutations （移碼突變）: involve the addition or deletion of nucleotides in multiples of one or two.,3、Consequence

17、s of Mutations- coding sequence,,如果你所研究的基因發(fā)生了突變，你將如何從遺傳學角度判斷他是錯義突變、無義突變還是移碼突變？,3、Consequences of Mutations- Noncoding sequence,為什么操縱子區(qū)（oprator）和啟動子(promoter)突變總是順式顯性和反式隱形突變？而編碼阻抑蛋白基因突變，則是順式還是反式顯性呢？,Mutations can occur

18、spontaneously or be inducedSpontaneous mutations(自發(fā)突變)Result from abnormalities in cellular/biological processesfor example： Errors in DNA replicationInduced mutations （誘發(fā)突變）Caused by environmental agentsAgents t

19、hat are known to alter DNA structure are termed mutagensThese can be chemical or physical agents,4、What Causes Mutations?,1、What Are Mutations?,4、What Causes Mutations?,3、Consequences of Mutations,2、 Features of Gene M