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1、Bacterial GeneticsXiao-Kui GUO PhD第一页，共四十二页。Bacterial Genomics第二页，共四十二页。Microbial Genomics第三页，共四十二页。第四页，共四十二页。第五页，共四十二页。68%Deinococcus radioduransMicrobial Genome FeaturesG+C content29%Borrelia burgdorferiGenome organizationsingle circular chromosomelarge linear chromosome plus21 extrachromosomal el
2、ementscircular chromosome plus one or moreextrachromosomal elementstwo circular chromosomes第六页，共四十二页。PLASMIDS Plasmidsareextrachromosomalgeneticelementscapableofautonomousreplication.Plasmidsareextrachromosomalgeneticelementscapableofautonomousreplication.AnAnepisomeepisomeisaplasmidthatcanintegrate
3、intothebacterialchromosomeisaplasmidthatcanintegrateintothebacterialchromosomeClassification of PlasmidsClassification of PlasmidsTransferpropertiesTransferpropertiesConjugative plasmidsConjugative plasmids Nonconjugative plasmidsPhenotypiceffectsPhenotypiceffects Fertility plasmid(F factor)Fertilit
4、y plasmid(F factor)Bacteriocinogenic plasmids.Resistance plasmids 7 factors)Resistance plasmids 7 factors).第七页，共四十二页。Insertionsequences(IS)-InsertionsequencesaretransposablegeneticelementsInsertionsequencesaretransposablegeneticelementsthatcarrynoknowngenesexceptthosethatarerequiredfortransposition.
5、thatcarrynoknowngenesexceptthosethatarerequiredfortransposition.a.a.NomenclatureNomenclature-InsertionsequencesaregiventhedesignationISfollowedbyanumber.e.g.IS1-InsertionsequencesaregiventhedesignationISfollowedbyanumber.e.g.IS1 b.b.StructureStructureInsertionsequencesaresmallstretchesofDNAthathavea
6、ttheirendsrepeatedsequences,whichareInsertionsequencesaresmallstretchesofDNAthathaveattheirendsrepeatedsequences,whichareinvolvedintransposition.Inbetweentheterminalrepeatedsequencestherearegenesinvolvedintranspositionandinvolvedintransposition.Inbetweentheterminalrepeatedsequencestherearegenesinvol
7、vedintranspositionandsequencesthatcancontroltheexpressionofthegenesbutnoothernonessentialgenesarepresent.sequencesthatcancontroltheexpressionofthegenesbutnoothernonessentialgenesarepresent.c.c.ImportanceImportance i)Mutation-Theintroductionofaninsertionsequenceintoabacterialgenewillresultintheinacti
8、vationofthei)Mutation-Theintroductionofaninsertionsequenceintoabacterialgenewillresultintheinactivationofthegene.gene.ii)Plasmidinsertionintochromosomes-Thesitesatwhichplasmidsinsertintothebacterialchromosomeareatornearinsertionii)Plasmidinsertionintochromosomes-Thesitesatwhichplasmidsinsertintotheb
9、acterialchromosomeareatornearinsertionsequenceinthechromosome.sequenceinthechromosome.iii)PhaseVariation-Theflagellarantigensareoneofthemainantigenstowhichtheimmuneresponseisdirectedinouriii)PhaseVariation-Theflagellarantigensareoneofthemainantigenstowhichtheimmuneresponseisdirectedinourattempttofig
10、htoffabacterialinfection.InSalmonellatherearetwogeneswhichcodefortwoantigenicallydifferentattempttofightoffabacterialinfection.InSalmonellatherearetwogeneswhichcodefortwoantigenicallydifferentflagellarantigens.Theexpressionofthesegenesisregulatedbyaninsertionsequences.Inoneorientationoneoftheflagell
11、arantigens.Theexpressionofthesegenesisregulatedbyaninsertionsequences.Inoneorientationoneofthegenesisactivewhileintheotherorientationtheotherflagellargeneisactive.Thus,Salmonellacanchangetheirflagellagenesisactivewhileintheotherorientationtheotherflagellargeneisactive.Thus,Salmonellacanchangetheirfl
12、agellainresponsetotheimmunesystemsattack.PhasevariationisnotuniquetoSalmonellaflagellarantigens.Itisalsoseeninresponsetotheimmunesystemsattack.PhasevariationisnotuniquetoSalmonellaflagellarantigens.Itisalsoseenwithotherbacterialsurfaceantigens.Alsothemechanismofphasevariationmaydifferindifferentspec
13、iesofbacteria(e.g.withotherbacterialsurfaceantigens.Alsothemechanismofphasevariationmaydifferindifferentspeciesofbacteria(e.g.Neisseria;transformation).Neisseria;transformation).第八页，共四十二页。Transposons(Tn)-Transposons are transposable genetic elements that carry one or Transposons are transposable gen
14、etic elements that carry one or more other genes in addition to those which are essential for transposition.more other genes in addition to those which are essential for transposition.NomenclatureNomenclature-Transposons are given the designation Tn followed by a -Transposons are given the designati
15、on Tn followed by a number.number.StructureStructure-The structure of a transposon is similar to that of an insertion sequence.The -The structure of a transposon is similar to that of an insertion sequence.The extra genes are located between the terminal repeated sequences.In some instances extra ge
16、nes are located between the terminal repeated sequences.In some instances(composite transposons)the terminal repeated sequences are actually insertion sequences.(composite transposons)the terminal repeated sequences are actually insertion sequences.ImportanceImportance-Many antibiotic resistance gen
17、es are located on transposons.-Many antibiotic resistance genes are located on transposons.Since transposons can jump from one DNA molecule to another,these Since transposons can jump from one DNA molecule to another,these antibiotic resistance transposons are a major factor in the development of an
18、tibiotic resistance transposons are a major factor in the development of plasmids which can confer multiple drug resistance on a bacterium harboring plasmids which can confer multiple drug resistance on a bacterium harboring such a plasmid.These multiple drug resistance plasmids have become a major
19、such a plasmid.These multiple drug resistance plasmids have become a major medical problem because the indiscriminate use of antibiotics have provided a medical problem because the indiscriminate use of antibiotics have provided a selective advantage for bacteria harboring these plasmidsselective ad
20、vantage for bacteria harboring these plasmids.第九页，共四十二页。第十页，共四十二页。Mechanism of bacterial variationGene mutationGene transfer and recombination TransformationTransformationConjugation Conjugation TransductionTransductionLysogenic conversion Protoplast fusion Protoplast fusion 第十一页，共四十二页。Types of muta
21、tionBase substitutionFrame shefitInsertion sequences第十二页，共四十二页。What can cause mutation?Chemicals:nitrous acid;alkylating agents5-bromouracilbenzpyreneRadiation:X-rays and Ultraviolet lightViruses第十三页，共四十二页。Bacterial mutationMutation rateMutation and selectivityBackward mutation第十四页，共四十二页。Transformat
22、ionTransformation is gene transfer resulting from the uptake by a recipient cell of naked DNA from a donor cell.Certain bacteria(e.g.Bacillus,Haemophilus,Neisseria,Pneumococcus)can take up DNA from the environment and the DNA that is taken up can be incorporated into the recipients chromosome.第十五页，共
23、四十二页。第十六页，共四十二页。第十七页，共四十二页。第十八页，共四十二页。第十九页，共四十二页。第二十页，共四十二页。Conjugation Transfer of DNA from a donor to a recipient by direct physical contact between the cells.In bacteria there are two mating types a donor(male)and a recipient(female)and the direction of transfer of genetic material is one way;DNA
24、 is transferred from a donor to a recipient.第二十一页，共四十二页。Physiological States of F FactorAutonomous(F+)Characteristics of F+x F-crossesF F-becomes F becomes F+while F while F+remains F remains F+Low transfer of donor Low transfer of donor chromosomal geneschromosomal genesF+第二十二页，共四十二页。Physiological
25、States of F FactorIntegrated(Hfr)Characteristics of Hfr x F-crossesF F-rarely becomes rarely becomes Hfr while Hfr Hfr while Hfr remains Hfrremains HfrHigh transfer of High transfer of certain donor certain donor chromosomal chromosomal genesgenesF+Hfr第二十三页，共四十二页。Physiological States of F FactorAuto
26、nomous with Autonomous with donor genes(F)donor genes(F)Characteristics of F x Characteristics of F x F F-crosses crossesF F-becomes F becomes F while F remains while F remains F FHigh transfer of High transfer of donor genes on donor genes on F and low F and low transfer of other transfer of other
27、donor donor chromosomal chromosomal genesgenesHfrF第二十四页，共四十二页。Mechanism of F+x F-CrossesDNA transferOrigin of transferRolling circle replication Pair formation Conjugation bridgeF+F-F+F-F+F+F+F+第二十五页，共四十二页。Mechanism of Hfr x F-CrossesDNA transferDNA transfer Origin of transferOrigin of transfer Roll
28、ing circle Rolling circle replicationreplicationHomologous Homologous recombinationrecombination Pair formation Conjugation bridgeHfrF-HfrF-HfrF-HfrF-第二十六页，共四十二页。Mechanism of F x F-CrossesDNA transfer Origin of transferOrigin of transfer Rolling circle Rolling circle replicationreplication Pair form
29、ation Conjugation bridgeFFFFFF-FF-第二十七页，共四十二页。R Plasmid第二十八页，共四十二页。Transduction:Transduction is defined as the transfer of genetic information between cells through the mediation of a virus(phage)particle.It therefore does not require cell to cell contact and is DNase resistant.第二十九页，共四十二页。Generaliz
30、ed Transduction Generalized transduction is transduction in which potentially any bacterial gene from the donor can be transferred to the recipient.第三十页，共四十二页。The mechanism of generalizedtransduction第三十一页，共四十二页。第三十二页，共四十二页。第三十三页，共四十二页。第三十四页，共四十二页。Generalized transduction1.It is relatively easy.2.It
31、is rather efficient(10It is rather efficient(10-3-3 per recipient with P22HT,10-6 with P22 or P1),using the correct with P22 or P1),using the correct phage.phage.3.It moves only a small part of the chromosome It moves only a small part of the chromosome which allows you to change part of a strains w
32、hich allows you to change part of a strains genotype without affecting the rest of the genotype without affecting the rest of the chromosome.chromosome.4.The high frequency of transfer and the small The high frequency of transfer and the small region transferred allows fine-structure region transfer
33、red allows fine-structure mappingmapping第三十五页，共四十二页。Specialized transductionSpecialized transductionSpecialized transduction is transduction in which is transduction in which only only certain donor genes genes can be transferred to can be transferred to the recipient.the recipient.Different phages
34、may transfer different genes but anDifferent phages may transfer different genes but an individual phage can only transfer certain genesindividual phage can only transfer certain genesSpecialized transduction is mediated by lysogenic or Specialized transduction is mediated by lysogenic or temperate
35、phage and the genes that get transferred temperate phage and the genes that get transferred will depend on where the prophage has inserted in will depend on where the prophage has inserted in the chromosome.the chromosome.第三十六页，共四十二页。The mechanism of specialized transduction第三十七页，共四十二页。Specialized t
36、ransduction 1.Very efficient transfer of a small region-can be useful Very efficient transfer of a small region-can be useful for fine-structure mapping for fine-structure mapping 2.Excellent source of DNA for the chromosomal region Excellent source of DNA for the chromosomal region carried by the p
37、hage,since every phage carries the carried by the phage,since every phage carries the same DNA.same DNA.3.Can often be used to select for deletions of some of the chromosomal genes carried on the phage.4.Merodiploids generated using specialized phage can be quite useful in complementation analyses.第
38、三十八页，共四十二页。Lysogenic conversion The prophage DNA as a gene recombined with chromosome of host cell.第三十九页，共四十二页。Protoplast Fusion Fusion of two protoplasts treated with lysozyme and penicillin.第四十页，共四十二页。Application of Bacterial VariationUse in medical clinic:Diagnosis,Treatment,Prophylaxis.Use in Genetic Engineering 第四十一页，共四十二页。内容(nirng)总结Bacterial Genetics。Xiao-Kui GUO PhD。Origin of transfer。Origin of transfer。Protoplast Fusion第四十二页，共四十二页。