整理课件 整理课件we are approaching the 100th anniversary of the fruit fly as amodel organism for studies in genetics and developmental biology In 1908,Thomas Hunt Morgan and his research associates at Columbia University placed rotting fruit on the window ledge of their laboratory.整理课件整理课件Among the menagerie of creatures that were captured,the fruit fly emerged as the animal of choice.Study the inheritance of quantitative traits,such as eye color.milk bottles,using inexpensive yeast and agarthe fruit fly adults produced large numbers of progeny innjust two weeks 整理课件整理课件One of the key processes that occurs during larval development is the growth of the imaginal disksThe growth of the imaginal disks:arising from invaginations of epidermis in mid-stage embryos.imaginal disks differentiate into their appropriate adult structures during metamorphosis(or pupation,蛹化蛹化)整理课件nThere is a pair of disks for every set of appendagesfor example,a set of foreleg imaginal disks a set of antennae imaginal disks a set of mouthpart imaginal disks -nDisks are composed of fewer than 100 cells in the embryo but ten thousands of cells in mature larvae.整理课件Figure 21-16 Imaginal disks(器官芽器官芽)in Drosophila整理课件nThe wing imaginal disk has become an important model system for the control of complex patterning processes by gradients of secreted signaling molecules.整理课件In 1910 the Morgan lab identified a spontaneous mutant male fly that had white eyes rather than the brilliant red seen for normal strains.This single fly lanched an incisive series of genetic studies-led two major discoveries:nGenes are located on chromosome nEach gene is composed of two allels整理课件Two allels assort independently during meiosis(Mendels first law)That genes located on separate chromosomes segregate independently(Mendels second law)Whreras those linked on the same chromosome do not.整理课件nMendels first law:Genes are located on chromosomes,and each gene is composed of two alleles that assort independently during meiosis.等位基因独立分离等位基因独立分离nMendels second law:Genes located on separate chromosomes segregate independently 不同染色体上不同染色体上的基因自由组合的基因自由组合(形成合子时形成合子时)整理课件Alfred H.Sturtevant(an undergradute at Columbia University,a member of the Morgan lab)developed a simple mathematical algorithm for mapping the distances between linked genes based on recombination frequenciesBy 1930s,extensive genetic maps were produced that identified the relative position of numerous gene controlling a variety of physical characteristics of the adult,such as wing size and shape,eye color.整理课件整理课件Useful features of the flies in experimental research:nFecunditynRapid life cyclenFour chromosomes(two large autosomes,a smaller X,and a very small fourth chromosome)整理课件Polytene chromosomesIn the salivary gland,extensive endoreplication without mitosis,Giant chromosomes composed of approximately 1000 copies of each chromatid-determine a physical map of the Drosophila genome整理课件Genetic map,deficiency mappingfirst correlate the occurrence of genes for certain traits with given physical segments of chromosomes,(phenotypes of flies white eyes were correlated with deletions in the chromosomesFigure 21-17 Polytene chromosomes整理课件nBridges used polytene chormosomes to determine a physical map of the Drosophila genome.identified 5000“bands”on the four chromosomes and established a correlation between the bands and the locations of genetic loci identified in the classical recombination maps.整理课件For example:Female fruit flies that are heterozygous for the recessive white mutation exhibit nomal red eyesFemale fruit flies that contain the white mutation and a small deletion in the other X chromosome,which removes polytene bands 3C2-3C3,exhibit white eyes.This type of analysis led to the conclusion:that the white gene is located between polytene bands 3C2-3C3 on the X chromosome整理课件nBalancer chromosomes contain inversions Figure 21-18整理课件nSuch balancers fail to undergo recombination with the native chromosome.Thus,it is possible to maintain fruit flies that contain recessive,lethal mutations.For example:nnull allele of eve and a balancer整理课件Embryos that are homozygous for this mutation die and fail to produce viable larvae and adultsThe null mutation can be maintained in a population that is heterozygous for a“nomal”chromosome containing the null allele of eve and a balancer second chromosome which contain a nomal copy of the gene.Since the eve null allele is strictly recessive,these flies are completely viable.整理课件Embryos that contain two copies of the balancer chromosome die,because of the invresions produce recessive disruption in critical genes.In addition,embryos that contain two copies of“nomal”chromosome die,because they are homozygous for the eve null mutation整理课件Mosaics are animals that contain small patches of mutant tissue in a generally“normal”genetic background.整理课件For example:Small pathes engrailed/engrailed homozygous mutant tissue can be produced by inducing mitotic recombination in developing larvae using X-rays.When such pathes are created in posterior regions of the developing wings,then the resulting flies exhibit abnomal wings that have duplicted anterior structure in place of the nomal posterior structureThe analysis of genetic mosaics provided the first evidence that engrailed is required for subdividing segments of flies into anterior and posterior compartments整理课件Sexual identity in flies is determined by the number of X chromosomes.(two-female;one-male)Y is needed for production of spermRarely,one of the two X chromosomes is lost at the(only)first mitotic division.整理课件nSuppose that one of the X chromosomes contains the recessive white allele.Then one half of the fly,the male half,has white eyes.While the other female half,has red eyes.整理课件Figure 21-19most spectacular genetic mosaics are gyandromorphs整理课件Drosophila:several favorable attributes for molecular studies and whole-genome analysis Approximately 150 Mb-5%mouse and humam fewer 14000 protein coding genesNew experimental method-producingstable transgenic strains carrying recombinant DNA整理课件Earlier,genetic Mosaics are produced by mitotic recombination in somatic tissurs.X-rays were used to induce recombination.it is inefficient-small pathes of mutant tissues More recently,The frequency of mitotic recombination was greatly enhanced by the use of the FLP recombinase from yeast.整理课件FLP recognizes FRT and catalyzes DNA rearrangement.整理课件整理课件整理课件整理课件整理课件This method is quite efficient.整理课件P-elements are transposable DNA segments that can cause hybrid dysgenesis.整理课件整理课件nSometimes the P-elements insert into genes that are essential for the development of progenitors of the gametes(配子配子),and,as a result,the adult flies derived from the these matings are sterile.整理课件Figure 21-21 hybrid dysgenesis nThe F1 progeny are often sterile,when mating females from the“M”strain with males from the“P”strain.整理课件整理课件整理课件P-elements can be used as vectors in the transformation of the fly embryos.Figure 21-22 整理课件整理课件整理课件整理课件整理课件 整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件整理课件Microinjection methods have been developed for the efficient expression of recombinant DNA in transgenic strain of mice.1,Inject DNA into the egg pronucleus.2,place the embryos into the oviduct(输卵管输卵管)of a female mouse.3,the injected DNA integrates at random positions in the genome.整理课件整理课件The efficiency of integration is quite high and usually occurs during early steges of development,often in one-cell embryos.As result,the fusion gene insert into most or all of the cells in the embryo,including the that form the somatic tissue and germline of the adult mouse that produced using this simple method of microinjection exhibit:germline transformation(生殖转化）生殖转化）:the offspring of transgenic mice also contain the foreign recombinant DNA.整理课件Figure 21-25转基因小鼠的原位表达转基因小鼠的原位表达A transgenic strain of mice was created that contains a portion of the Hoxb-2 regulatory region attached to a lacZ report gene.There are two bands of staining detected in the hindbrain region of 10.5 day embryos.整理课件 The single most powerful method of mouse transgenesis is the ability to disrupt,or“knock out,”single genetic loci.This permits the creation of mouse models for human disease.整理课件For example,the p53 gene encodes a regulatory protein that activates the expression of genes required for DNA repair.when p53 fuction is lost,cancer cells become highly invasive due to rapid accumulation of DNA mutations.A strain of mice has been established that is completely normal except for the removal of the p53 gene.These mice are highly susceptible to cancer,die young.-drug discovery整理课件culturing mouse blastocyst so ICM cells proliferate without diferentiatingmodified by deleting a small region near the beginning of the gene 整理课件.整理课件nThe process of the experiment整理课件整理课件整理课件整理课件整理课件整理课件整理课件Figure 21-27 imprinting in the mouse整理课件n作业：作业：n一、说出下列五种模式生物（一、说出下列五种模式生物（Model Organisms）的特点）的特点nEscherichia coli nphagenyeastnnematodenfruit fly nmouse整理课件n二、翻译下列英文单词并作简单解释二、翻译下列英文单词并作简单解释nprophagenBacteriophagenSexual Conjugation nPhage-Mediated TransductionnDNA-Mediated Transformationnhigh frequency recombinationnFluorescence in situ hybridization neukaryotic cellsnsporulationnGenetic complementationnhomologous recombination nOrphans familiesnDauer larva ntyrosine kinase napoptosis。