Genetics: From genes to genomes - Chapter 4: Basic principles: how traits are transmitted

*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or displayPowerPoint to accompanyGenetics: From Genes to GenomesFourth EditionLeland H. Hartwell, Leroy Hood, Michael L. Goldberg, Ann E. Reynolds, and Lee M. SilverPrepared by Mary A. BedellUniversity of GeorgiaCHAPTER OUTLINE*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4CHAPTERBasic Principles: How Traits Are TransmittedCHAPTERPART IThe Chromosome Theory of Inheritance4.1 Chromosomes: The Carriers of Genes4.2 Mitosis: Cell Division That Preserves Chromosome Number4.3 Meiosis: Cell Divisions That Halve Chromosome Number4.4 Gametogenesis4.5 Validation of the Chromosome TheoryChromosomes are cellular structures that transmit genetic informationBreeding experiments and microscopy provided evidence for the chromosome theory of inheritanceProper development relies on accurate transmission of genes and accurate maintenance of chromosome numberThe abstract idea of a gene was changed to a physical reality by the chromosome theoryCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Evidence that genes reside in the nucleus1667 - Anton Van LeeuwenhoekMicroscopy revealed that semen contain spermatozoa ("sperm animals")Hypothesized that sperm may enter egg to achieve fertilization1854 – 1874Direct observations of fertilization through union of nuclei of eggs and sperm (frog and sea urchin) Conclusion: something in the nucleus must contain the hereditary materialCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Evidence that genes reside in chromosomes1880s – improved microscopy and staining techniquesLong, threadlike bodies (chromosomes) visualized in the nucleusMovement of these bodies followed through cell divisionMitosis - nuclear division that generates two daughter cells containing the same number and type of chromosomes as parent cellMeiosis - Nuclear division that generates gametes (egg and sperm) containing half the number of chromosomes found in other cellsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Diploid versus haploid: 2n versus nMost body cells are diploid (each chromosome pair has one maternal and one paternal copy)Meiosis  haploid (n) gametesIn Drosophila, 2n = 8, n = 4In humans , 2n = 46 and n = 23Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.2Fertilization is the union of haploid gametes to produce diploid zygotesFertilized eggs carry matching sets of chromosomes, one set from maternal gamete and one set from paternal gameteGametes are haploid (n) – carry only a single set of chromosomesZygotes are diploid (2n) – carry two matching set of chromosomeMitosis ensures that all cells of developing individuals have identical 2n chromosome setsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Metaphase chromosomes can be classified by centromere positionMetacentric chromosome – centromere is in the middleAcrocentric chromosome – centromere is near one endCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.3Homologous chromosomes are matched in size, shape , and banding patternsHomologs contain the same set of genes, but can have different alleles for some genesNonhomologs carry completely unrelated sets of genes Karyotype – micrograph of stained chromosomes arranged in homologous pairs (see Fig 4.4)Sex chromosomes – unpaired X and Y chromosomeAutosomes – all chromosomes except X and YCells of each species have a characteristic diploid number of chromosomese.g. D. melanogaster, 2n = 8; D. obscura, 2n = 10; D. virilis, 2n = 12; sweet peas, 2n = 14; goldfish, 2n = 94; dogs, 2n = 78Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Karyotype of a human malePhotos of metaphase human chromosomes (2n = 46, n = 23)Each homologous pair arranged in order of decreasing sizeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.4One chromosome pair determines sex in grasshoppersW. S. Sutton studied meiosis in great lubber grasshoppers Before meiosis, testes cells had 24 chromosomes22 in matched pairs (autosomes) and 2 unmatched (large = X and smaller = Y)After meiosis, two types of sperm were formed1/2 of sperm had 11 chromosomes and an X1/2 of sperm had 11 chromosomes and a YAfter meiosis, only one type of egg was producedAll had 11 chromosomes plus an XCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*The great lubber grasshopperFertilization of egg with sperm carrying an X  XX femaleFertilization of egg with sperm carrying a Y  XY maleSutton concluded that the X and Y chromosomes determine sexCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.5The X and Y chromosomes determine sex in humansChildren receive an X chromosome from their mother, but either an X or Y chromosome from their fatherResults in 1:1 ratio of females-to-malesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.6Sex determination in fruit flies and humansIn Drosophila, ratio of X chromosomes to autosomes determines genderIn humans, presence or absence of Y chromosome determines gender Abnormal numbers of X or Y chromosomes have different effects in humans and flies Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Table 4.1Mechanisms of sex determination differ between speciesHeterogametic sex – gender with two different kinds of gametes (e.g. XY males in humans, ZW females in birds)Homogametic sex – gender with one type of gamete (e.g. XX females in humans, ZZ males in birds)In some species, gender is determined by environment (e.g. temperature)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Table 4.2The cell cycle is a repeating pattern of cell growth and divisionNuclear division during mitosis apportions chromosomes in equal fashion to two genetically identical daughter cellsInterphase has three parts - gap 1 (G1) phase, synthesis (S) phase, and gap 2 (G2) phasePeriod of cell growth and chromosome duplication between divisionsFormation of microtubules in cytoplasmCentrosome – microtubule organizing center near the nuclear envelopeCentrioles – core of centrosome, not found in plant cellsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*The cell cycle: An alternation between interphase and mitosisMost of cell growth occurs during G1 and G2 phasesSome terminally differentiated cells stop dividing and arrest in G0 stageChromosomes replicate to form sister chromatids during S phaseCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.7aChromosomes replicate during S phaseG1 phase – chromosomes are not duplicating or dividingLength of time varies in different cell typesS phase – duplication of chromosome into sister chromatidsG2 phase – synthesis of proteins required for mitosisCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.7bMitosis has five stages that have distinct cytological characteristics The five stages of mitosis and their major eventsProphase - chromosomes condense and become visiblePrometaphase – spindle forms and sister chromatids attach to microtubules from opposite centrosomesMetaphase – chromosome align at the cell's equatorAnaphase – sister chromatids separate and move to opposite polesTelophase – chromosomes decondense and are enclosed in two nucleiCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Stages of mitosis: prophaseChromosomes condense and become visibleCentrosomes move apart toward opposite polesNucleoli begin to disappearCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Figure 4.8aStages of mitosis: prometaphaseCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Figure 4.8bNuclear envelope breaks downMicrotubules from centrosomes invade the nucleus and connect to kinetochores in centromere of each chromatid Sister chromatids attach to microtubules from opposite polesMitotic spindle forms from three kinds of microtubules (astral, kinetochore, and polar)Stages of mitosis: metaphaseChromosomes align on the metaphase plate with sister chromatids facing opposite polesForces pushing and pulling chromosomes to or from each pole are in balanced equilibriumCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Figure 4.8cStages of mitosis: anaphaseCentromeres of all chromosomes divide simultaneouslyKinetochore microtubules shorten and pull separated sister chromatids to opposite poles (characteristic V shape)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Figure 4.8dStages of mitosis: telophaseRewind of prophaseNuclear envelope forms around each group of chromatids Nucleoli re-formSpindle fibers disperseChromosomes decondenseCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Figure 4.8eCytokinesis is the final stage of cell divisionBegins during anaphase but not completed until after telophaseParent cells split into two daughter cells with identical nucleiCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Figure 4.8fCytokinesis: The cytoplasm divides and produces two daughter cellsAnimals have contractile ring that contracts to form cleavage furrowPlants have cell plate that forms near equator of cellOrganelles (e.g. ribosomes, mitochondria, Golgi bodies) are distributed to each daughter cellCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.9Cytokinesis does not always occur after mitosisIn fertilized Drosophila eggs, 13 rounds of mitosis occur without cytokinesisResults in syncytial embryo with thousands of nuclei within a single cellCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.10Checkpoints help regulate the cell cycleAt each checkpoint, prior events must be completed before the next step of the cycle can beginDetails of cell-cycle regulation and checkpoint controls are described in Chapter 17Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.11Two general types of cells in plants and animalsSomatic cells make up vast majority of cells in the organismIn G0 or are actively going through mitosisGerm cells are precursors to gametesSet aside from somatic cells during embryogenesisBecome incorporated into reproductive organsOnly cells that undergo meiosis produce haploid gametesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Overview of meiosisCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.12Two rounds of meiosisChromosomes duplicate onceNuclei divide twiceOverview of meiosis IHomologs pair, exchange parts, and then segregateSister chromatids remain intact throughout meiosis IMaternal and paternal homologs recombine and create new combinations of allelesAfter recombination, homologs segregate to different daughter cellsFive substages to prophase I – leptotene, zygotene, pachytene, diplotene, and diakinesisDepending on the species, length of time in prophase I can be short or very long Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*The first three substages of prophase I:Leptotene, zygotene, and pachyteneHomologs pair and are held together by synaptonemal complexCrossing-over (recombination) occurs during prophase ICopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Feature Fig. 4.13The last two substages of prophase :Diplotene and diakinesisSynaptonemal complex dissolves and chromatids in each tetrad become visibleCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Feature Fig. 4.13In metaphase I and anaphase I, homologs move to opposite polesNote that the centromeres do not divide and sister chromatids are not separatedCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Feature Fig. 4.13Meiosis I is a reductional divisionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Feature Fig. 4.13During meiosis II, sister chromatids separate and move to opposite polesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Feature Fig. 4.13Meiosis II is an equational divisionCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Feature Fig. 4.13Prophase I of meiosis at very high magnificationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.14Mistakes in meiosis produce defective gametesNondisjunction – mistakes in chromosome segregation during meiosis I or IIMay result in inviable gametes or embryosCan also result in abnormal chromosome numbers in viable individuals (e.g. trisomy 21, Down syndrome; or XXY, Klinefelter syndrome)Many hybrids between species (i.e. donkey x horse  mule) are sterile because chromosomes cannot pair properly (hybrid sterility, see Figure 4.15)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Meiosis contributes to genetic diversity in two waysIndependent assortment of nonhomologs creates different combinations of allelesCrossing-over between homologs creates different combinations of alleles within each chromosomeCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.16Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Table 4.3Comparison of mitosis and meiosisCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Table 4.3Comparison of mitosis and meiosis (continued)Gametogenesis in sexually reproducing animalsGerm line – specialized diploid cells set aside during embryogenesisGametogenesis – the formation of gametesInvolves meiosis as well as specialized events before and after meiosisDifferent types of animals have variations on general aspects of this processIn humans, oogenesis produces one ovum from each primary oocyteIn humans, spermatogenesis produces four sperm from each primary spermatocyteCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Oogenesis in humansOogonia – diploid germ cells in ovaries of female embryosDivide by mitosis and enter meiosis I to become primary oocytesPrimary oocytes arrest in diplotene stage of meiosis I until after birthAt puberty, one oocyte per month resumes meiosisAt ovulation, completion of meiosis I produces a secondary oocyte and first polar bodySecondary oocyte arrests in metaphase of meiosis IIIf oocyte is fertilized, meiosis II is completed and produces a mature ovum and second polar bodyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*In humans, egg formation begins in the fetal ovaries and arrests during prophase of meiosis ICopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.17One ovum and 2 – 3 nonfunctional polar bodies produced by asymmetrical meiosisLong meiotic arrest may contribute to chromosome segregation errors (e.g. trisomies)Spermatogenesis in humansSpermatogonia – diploid germ cells found only in testisDivide by mitosis throughout lifespan of individualAfter birth, meiosis begins and spermatogonia become primary spermatocytesPrimary spermatocytes undergo symmetrical division at meiosis I to produce two secondary spermatoctyesSecondary spermatocytes undergo symmetrical division at meiosis II to produce two spermatidsSpermatids mature to become spermEqual numbers of X and Y sperm are producedCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Human sperm form continuously in the testes after pubertyCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.18Four haploid sperm produced by symmetrical meiosis of each spermatocyteMitosis and meiosis occur throughout adult lifeThe chromosome theory of inheritanceWalter Sutton – 1903, chromosomes carry Mendel's units of heredityTwo copies of each kind of chromosomeChromosome complement is unchanged during transmission to progenyHomologous chromosomes separate to different gametesMaternal and paternal chromosomes move to opposite polesFertilization of eggs by random encounter with spermIn all cells derived from fertilized egg, half of chromosomes are maternal and half are paternalCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*How the chromosome theory of inheritance explains Mendel's law of segregationTable 4.4aCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*How the chromosome theory of inheritance explains Mendel's law of independent assortmentTable 4.4bValidation of the chromosome theoryPrior to 1910, the chromosome theory of inheritance was supported by two circumstantial lines of evidenceSex determination associates with inheritance of particular chromosomes Events in mitosis, meiosis, and gametogenesis ensure constant numbers of chromosomes in somatic cellsThis theory confirmed and validated by:Inheritance of genes and chromosomes correspond in every detailTransmission of particular chromosome coincides with transmission of traits other than for sex determinationCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Nomenclature for Drosophila geneticsGene symbol identified by abnormal phenotypeWild-type allele denoted with superscript +Recessive mutant allele denoted with lowercasee.g. gene symbol for white gene is wwild-type allele (w+) specifies brick-red eyesmutant allele (w) specifies white eyesDominant mutant allele denoted with upper casee.g. gene symbol for bar eyes is Barwild-type allele (Bar+) specifies normal eyemutant allele (Bar) specifies abnormal eyesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*The Drosophila white gene is located on the X chromosomeT. H. Morgan (1910) discovered a white-eyed Drosophila mutant and did a series of crossesCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.19Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.19Crisscross inheritance occurs with X-linked recessive traitsSee cross D – daughters inherit the phenotype of their fathers, sons inherit the phenotype of their mothers Rare mistakes in meiosis helped confirm the chromosome theoryCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.20aC. Bridges found 1/2000 male progeny of white females have red eyesHypothesized that red-eyed males arise from mistakes in chromosome segregation (nondisjunction) during meiosis in white-eyed femalesRare mistakes in meiosis helped confirm the chromosome theory (cont)Chromosome segregation in an XXY femaleThe three sex chromosomes pair and segregate in two ways, producing progeny with unusual sex chromosome complementsCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.20bExample of an X-linked trait in humansCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.21(Top) View of the world to a person with normal color vision(Bottom) View of the world to a person with red-green colorblindnessE. B. Wilson – 1911, assigned gene for this trait to the X chromosomeAn example of a pedigree for an X-linked recessive trait: HemophiliaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.22aAn example of a pedigree for an X-linked dominant trait: HypophosphatemiaCopyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.22bAutosomal genes and sexual dimorphismSex-influenced traitsAppear in both sexes but hormonal differences may cause differencee.g. male pattern baldness (right, in John Adams and John Quincy Adams)Copyright © The McGraw-Hill Companies, Inc. Permission required to reproduce or display Hartwell et al., 4th ed., Chapter 4*Fig. 4.23Sex-limited traits Affect a structure or process found in only one sexe.g. Drosophila stuck mutant males can't separate from female after mating