Chromosomes and Sex-Chromosome Inheritance

CHAPTER 4 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORChromosomes SALE OR DISTRIBUTION NOT FOR SALE and OR DISTRIBUTION

Sex-Chromosome© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC InheritanceNOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION CHAPTER OUTLINE Chromosomes come in pairs, one from the mother and the other from the father. Human cells have 23 pairs of 4.1 The Stability of Chromosome Complements chromosomes—46 chromosomes altogether. [© Hybrid Medical/Photo Researchers, Inc.] 4.2 Mitosis © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Meiosis 4.3 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4.4 Sex-Chromosome Inheritance 4.5 Probability in the Prediction of Progeny Distributions 4.6 Testing Goodness of Fit to a Genetic Hypothesis CONNECTION Grasshopper, Grasshopper E. Eleanor Carothers© Jones 1913 & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC The MendelianNOT Ratio FORin Relation SALE to Certain OR Orthopteran DISTRIBUTION Chromosomes NOT FOR SALE OR DISTRIBUTION CONNECTION The White-Eyed Male Thomas Hunt Morgan 1910 Sex-Limited Inheritance in Drosophila CONNECTION Seeds of Doubt © JonesRonald & Aylmer Bartlett Fisher Learning, 1936 LLC © Jones & Bartlett Learning, LLC Has Mendel’s Work Been Rediscovered? NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

26105_CH04_116_153.indd 116 4/27/11 9:32 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

LEARNING OBJECTIVES & SCIENCE COMPETENCIES

Understanding how© chromosomesJones & Bartlett and sex-chromosomes Learning, LLC are inherited as well as the© basicJones principles & Bartlett of probability Learning, LLC and statistical testsNOT of hypothesesFOR SALE discussed OR DISTRIBUTION in this chapter will allow you toNOT satisfy FOR the SALEfollowing OR science DISTRIBUTION competencies: ■ Predict what products of mitosis or meiosis would result from normal chromosome behavior or chromosome misbehavior. ■ Recognize the characteristic pattern of X-linked inheritance, and be able to trace X chromosomes as they pass ©between Jones the & sexesBartlett from Learning, generation toLLC generation. © Jones & Bartlett Learning, LLC ■ NOTGiven FOR a genetic SALE cross, OR use DISTRIBUTION the binomial distribution to calculate NOTthe probability FOR SALE of any OR particular DISTRIBUTION combination of genotypes or phenotypes among the progeny. ■ Be able to formulate a genetic hypothesis, use it to predict expected results of a cross, and compare the expected results with observed results by means of a chi-square test for goodness of fit. Interpret the results of the test © Jones & Bartlettaccording Learning, to whether LLC or not the hypothesis should© Jones be rejected. & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

t came as no great revelation that genes are located in chromosomes. The parallel Ibetween their properties© Jones made & Bartlett this quite Learning, LLC © Jones & Bartlett Learning, LLC obvious: NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 1. Genes come in pairs; chromosomes come in pairs. 2. Alleles of a gene segregate; homologous chromosomes segregate. 3.© UnlinkedJones & genes Bartlett undergo Learning, independent LLC © Jones & Bartlett Learning, LLC assortment; nonhomologous chromo- NOTsomes FOR undergo SALE independent OR DISTRIBUTION assortment. NOT FOR SALE OR DISTRIBUTION These parallels were first pointed out in MICROTUBULAR cytoskeleton of the African globe amaryllus (Scadoxus), which becomes transformed into the spindle in 1903, and after that time there was little doubt mitosis, as seen through a light microscope. [© Andrew S. that chromosomes are the cellular carriers of the Bajer/Bajer Research Projects.] © Jones &genes. Bartlett But parallels Learning, do not LLC constitute scientific © Jones & Bartlett Learning, LLC proof, nor does widespread agreement among years later, chromosomes were found to segregate NOT FORscientists. SALE ORIn this DISTRIBUTION chapter we shall examine some byNOT an orderly FOR SALEprocess OR into DISTRIBUTION the daughter cells of the experimental evidence that was at the formed by cell division as well as into the gametes time—and still is—regarded as sufficient to formed by the division of reproductive cells. prove the chromosome theory of heredity. Three important regularities were observed about © Jones & Bartlett Learning,the chromosome LLC complement (the© Jones complete & Bartlett Learning, LLC set of chromosomes) of plants and animals. 4.1 The StabilityNOT of Chromosome FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Complements 1. The nucleus of each somatic cell (a cell of the body, in contrast to a germ cell, The cell nucleus was first discovered in 1831, but or gamete) contains a fixed number of not until the late 1860s was it understood that chromosomes typical of the particular nuclear© Jones division &nearly Bartlett always Learning, accompanies LLC cell species. This© Jones number & variesBartlett tremen- Learning, LLC division. The importance of the nucleus in inheri- dously among species, and chromosome tanceNOT was reinforced FOR SALE by the OR nearly DISTRIBUTION simultaneous number bearsNOT little FOR relation SALE to theOR com- DISTRIBUTION discovery that the nuclei of two gametes fuse in plexity of the organism (TABLE 4.1). the process of fertilization. The next major 2. The chromosomes in the nuclei of advance came in the 1880s with the discovery of somatic cells are usually present in © Jones &chromosomes Bartlett Learning,, easily visualized LLC in the light © Jonespairs. &For Bartlett example, Learning, the 46 chromo-LLC microscope with the use of certain dyes. A few somes of human beings consist of 23 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.1 The Stability of Chromosome Complements 117

26105_CH04_116_153.indd 117 4/27/11 9:32 AM © Jones & BartlettTable 4.1 Learning,Somatic (diploid)LLC chromosome numbers of ©some Jones plant and & animalBartlett species Learning, LLC NOT FOR SALEOrganism OR DISTRIBUTION Chromosome numberNOT OrganismFOR SALE OR DISTRIBUTIONChromosome number Field horsetail 216 Yeast (Saccharomyces cerevisiae) 32 Bracken fern 116 Fruit fly (Drosophila melanogaster) 8 Giant sequoia 22 Nematode (Caenorhabditis elegans) 11 (, 12 & Macaroni wheat © Jones & Bartlett Learning, 28 LLC House fly © Jones & Bartlett 12 Learning, LLC Bread wheat NOT FOR SALE OR DISTRIBUTION 42 Scorpion NOT FOR SALE 4 OR DISTRIBUTION Fava bean 12 Geometrid moth 224 Garden pea 14 Common toad 22 Mustard cress (Arabidopsis thaliana) 10 Chicken 78 Corn (Zea mays) 20 Mouse 40 ©Lily Jones & Bartlett Learning, LLC 24 Gibbon © Jones & Bartlett Learning, 44 LLC NOTSnapdragon FOR SALE OR DISTRIBUTION 16 Human beingNOT FOR SALE OR DISTRIBUTION 46

pairs (FIGURE 4.1). Cells with nuclei that and the other from the paternal parent © Jones & Bartlett Learning,contain LLC two similar sets of chromo-© Jones & Bartlettof the Learning, organism. LLC somes are called diploid. A diploid 3. The gametes that unite in fertilization NOT FOR SALE OR DISTRIBUTIONindividual carries two alleleic copiesNOT ofFOR SALE toOR produce DISTRIBUTION the diploid somatic cells each gene present in each pair of chro- have nuclei that contain only one set of mosomes. The chromosomes occur in chromosomes, consisting of one mem- pairs because one chromosome of each ber of each pair. The gametic nuclei are ©pair Jones derives & fromBartlett the maternalLearning, parent LLC haploid. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

FIGURE 4.1 Chromosome complement of a human male. There are 46 chromosomes, present in 23 pairs. At the stage of the division cycle in which these chromosomes were observed, each chromosome consists of two identical halves lying side by side longitudinally. Except for the members of one chromosome pair (the pair that determines sex), the members of all the chromosome © Jones & Bartlett Learning,pairs are the same LLC color because they contain DNA molecules© Jones that were& Bartlett labeled with Learning,the same mixture LLC of fluorescent dyes. The colors differ from one pair to the next because the dye mixtures differ in color. In some cases, the long and the short arm have been labeled NOT FOR SALE OR DISTRIBUTIONwith a different color. [Courtesy of Michael R. Speicher,NOT Institute FOR of Genome SALE Genetics, OR MedicalDISTRIBUTION University of Graz.]

118 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 118 4/27/11 9:32 AM In multicellular organisms that develop be seen. This stage of the cell cycle is called © Jones from& Bartlett single cells,Learning, the presence LLC of the diploid interphase© Jones .& In Bartlett preparation Learning, for mitosis, LLC the NOT FORchromosome SALE OR number DISTRIBUTION in somatic cells and of the DNANOT in FORthe chromosomes SALE OR is DISTRIBUTION replicated during a haploid chromosome number in germ cells indi- period of interphase called S (FIGURE 4.2), which cates that there are two processes of nuclear stands for synthesis of DNA. DNA replication is division that differ in their outcome. One of accompanied by chromosome duplication. these (mitosis) maintains the chromosome Before and after S, there are periods, called © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC number; the other (meiosis) reduces the num- G1 and G2, respectively, in which DNA replica- ber by half. These twoNOT processes FOR are SALE examined OR DISTRIBUTION tion does not take place. The cell cycleNOT (the FOR life SALE OR DISTRIBUTION in the following sections. cycle of a cell) is commonly described in terms of these three interphase periods followed by 4.2 Mitosis mitosis, M. The order of events is therefore G1 ǞSǞG2 ǞM, as shown in Figure 4.2. In this Mitosis© Jones is a process & Bartlett of nuclear Learning, division LLCthat representation, the© MJones period & also Bartlett includes Learning, the LLC ensuresNOT that FOR each ofSALE two daughter OR DISTRIBUTION cells receives a division of the cytoplasmNOT FOR (cytokinesis) SALE intoOR twoDISTRIBUTION diploid complement of chromosomes identical to approximately equal parts, each containing one the diploid complement of the parent cell. Mitosis daughter nucleus. The length of time required is usually accompanied by cytokinesis, the pro- for a complete life cycle varies with cell type; it cess in which the cell itself divides to yield two is 18–24 hours for the majority of cells in higher © Jones &daughter Bartlett cells. Learning, The basic LLCprocess of mitosis is eukaryotes.© Jones The& Bartlett relative duration Learning, of the LLC differ- NOT FORremarkably SALE OR uniform DISTRIBUTION in all organisms: entNOT periods FOR in theSALE cycle OR also DISTRIBUTION varies considerably 1. Each chromosome is already present as a with cell type. Mitosis is usually the shortest duplicated structure at the beginning of period, requiring 0.5–2 hours. nuclear division. (The duplication of each The cell cycle is an active, regulated process chromosome coincides with the replica- controlled by mechanisms that are essentially tion of the DNA© moleculeJones &it contains.)Bartlett Learning,identical LLC in all eukaryotes. These are© Jones discussed & Bartlett Learning, LLC 2. Each chromosomeNOT FORdivides SALE longitudi- OR DISTRIBUTIONin detail in Chapter 15. The transitionsNOT from FOR G1 SALE OR DISTRIBUTION nally into identical halves that separate into S and from G2 into M are called check- from each other. points because the transitions are delayed 3. The separated chromosome halves unless key processes have been completed (Fig- move in opposite directions, and each ure 4.2). For example, at the G1 S checkpoint, © becomesJones &included Bartlett in Learning,one of the LLCtwo either sufficient time© Jones must have & Bartlett elapsed sinceLearning, LLC NOTdaughter FOR nuclei SALE that OR are DISTRIBUTION formed. the preceding mitosisNOT (in FOR some SALEcell types) OR or DISTRIBUTION (in In a cell not undergoing mitosis, the chro- other cell types) the cell must have attained suf- mosomes are invisible with a light microscope. ficient size for DNA replication to be initiated. Each consists of an elongated thread too thin to Similarly, the G2 M checkpoint requires that © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC

NOT FOR SALE OR DISTRIBUTION S (DNA synthesis)NOT FOR SALE OR DISTRIBUTION

r u

NOT FOR SALE OR DISTRIBUTION G2 (Post-DNA synthesis)NOT FOR SALE OR DISTRIBUTION

G /S checkpoint s

Start r 1

4 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC

NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

1 0 h o u r s ur ho G (Pre-DNA synthesis) 1 1 G2/M checkpoint © Jones & Bartlett Learning, LLC © JonesM (mitosis) & Bartlett Learning, LLC NOT FORFIGURE SALE 4.2 ORThe cell DISTRIBUTION cycle of a typical mammalian cell growing in tissueNOT culture FOR with a SALEgeneration OR time ofDISTRIBUTION 24 hours.

4.2 Mitosis 119

26105_CH04_116_153.indd 119 4/27/11 9:32 AM DNA replication and repair of any DNA damage of the nuclear envelope. (These processes are © Jones & Bartlett Learning,be completed LLC for the M phase to commence.© Jones & discussedBartlett inLearning, more detail LLC in Chapter 15.) NOT FOR SALE OR DISTRIBUTIONIllustrated in FIGURE 4.3 are the essentialNOT fea- FOR SALEThe OR spindle DISTRIBUTION features three types of microtu- tures of chromosome behavior in mitosis. Mito- bules: (1) those that anchor the centrosome to sis is conventionally divided into four stages: the cell membrane, (2) those that arch between prophase, metaphase, anaphase, and telo- the centrosomes, and (3) those that become phase. (If you have trouble remembering the attached to the chromosomes. The manner order,© you Jones can jog & Bartlettyour memory Learning, with “p LLCeas in which these are© established Jones & exemplifiesBartlett Learning, an LLC make aNOTwful tFORarts.”) SALEThe stages OR have DISTRIBUTION the follow- important organizingNOT principle FOR ofSALE biology OR that DISTRIBUTION ing characteristics: may be called exploration and stabilization. As microtubules are formed, new tubulin subunits 1. Prophase In interphase, the chro- are added to the growing end of the polymer, mosomes have the form of extended but the growing end can also become unsta- © Jones & Bartlettfilaments Learning, and cannot beLLC seen with a light ble© and Jones initiate & aBartlett process ofLearning, depolymerization LLC NOT FOR SALEmicroscope OR DISTRIBUTION as discrete bodies. Except for in NOTwhich FOR the SALEmicrotubule OR DISTRIBUTIONshrinks. Several the presence of one or more conspicuous proteins help regulate the balance between dark bodies (nucleoli), the nucleus has a polymerization and depolymerization. In spin- diffuse, granular appearance. The begin- dle formation, microtubules grow out from the ning of prophase is marked by the con- spindle poles in essentially random directions © Jones & Bartlett Learning,densation LLC of chromosomes to form© visibly Jones & (thisBartlett is the Learning,exploration partLLC of the process), but NOT FOR SALE OR DISTRIBUTIONdistinct threads within the nucleus.NOT Chro- FOR SALEunless somethingOR DISTRIBUTION happens to stabilize the grow- matin condensation is brought about by ing end, each polymer will ultimately undergo PROPHASE of Scadoxus. large protein complexes known as con- [© Andrew S. Bajer/Bajer depolymerization and disappear. For the micro- Research Projects] densins. At this stage each chromosome is tubules that become attached to the chromo- already longitudinally double, consisting somes, the event that stabilizes the growing end of two© closely Jones associated & Bartlett subunits Learning, called chro- LLC is contact with a structure© Jones technically & Bartlett known Learning, LLC matidsNOT. The FOR longitudinally SALE OR bipartite DISTRIBUTION nature of as the kinetochoreNOT, which FOR coincidesSALE OR with DISTRIBUTION each chromosome is readily seen later in pro- the position of the centromere. The process of phase. Each pair of chromatids is the product random exploration and stabilization thereby of the duplication of one chromosome in the S results in a situation in which only those chro- period of interphase. The chromatids in a pair mosomal microtubules that make contact with © Jonesare & Bartlettheld together Learning, at a specific LLC region of the a kinetochore© Jones &become Bartlett stabilized Learning, and the LLC others NOT FORchromosome SALE OR called DISTRIBUTION the centromere. As pro- depolymerize.NOT FOR AnalogousSALE OR types DISTRIBUTION of stabilization phase progresses, the chromosomes become likely also account for the microtubules that shorter and thicker as a result of intricate coil- attach to the cell membrane and those that arch ing (Chapter 7). At the end of prophase, the between the centrosomes. nucleoli disappear and the nuclear envelope, a After the spindle fibers have become at- © Jones & Bartlett Learning,membrane LLCsurrounding the nucleus, abruptly© Jones & tachedBartlett to theLearning, chromosomes, LLC each chromosome NOT FOR SALE OR DISTRIBUTIONdisintegrates. NOT FOR SALEis moved OR to DISTRIBUTIONa position near the center of the cell where its kinetochore lies on an imagi- 2. Metaphase At the beginning of metaphase, nary plane approximately equidistant from the the mitotic spindle forms. The spindle is an spindle poles. This imaginary plane is called the elongated, football-shaped array of spindle metaphase plate. Aligned on the metaphase fibers ©consisting Jones &primarily Bartlett of Learning, microtubules LLC plate, the chromosomes© Jones reach &their Bartlett maximum Learning, LLC formedNOT by polymerization FOR SALE ofOR the DISTRIBUTION protein tubu- condensation and areNOT easiest FOR to count SALE and OR exam- DISTRIBUTION lin. Many other proteins and at least one ine for differences in shape and appearance. RNA-protein complex regulate tubulin poly- Proper chromosome alignment is an impor- merization and microtubule organization. The tant cell cycle control checkpoint at metaphase ends or poles of the spindle, where the microtu- in both mitosis and meiosis. In a cell in which a © Jonesbules & Bartlett converge, Learning, mark the locationsLLC of the cen- chromosome© Jones is& attached Bartlett to Learning,only one pole LLC of the NOT FORtrosomes SALE, which OR DISTRIBUTIONare the microtubule organizing spindle,NOT the FOR completion SALE ofOR metaphase DISTRIBUTION is delayed. METAPHASE of Scadoxus. centers where tubulin polymerization is initi- The signal for proper chromosome alignment [© Andrew S. Bajer/Bajer comes from the kinetochore, and the chemical Research Projects.] ated. Each pair of centrosomes results from the duplication of a single centrosome that takes nature of the signal seems to be the dephosphor- place in interphase, followed by migration of ylation of certain kinetochore-associated pro- © Jones & Bartlett Learning,the daughter LLC centrosomes to opposite© Jonessides & teins.Bartlett Through Learning, the signaling LLC mechanism, when NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

120 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 120 4/27/11 9:32 AM Nuclear envelope © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning,In this chromosome LLC the sister chromatids are NOT FOR SALE OR DISTRIBUTION ChromatidNOT FOR SALE OR DISTRIBUTION Centromere distinguished by color. Nucleolus

MITOSIS

Pole © Jones & Bartlett Learning,Anaphase LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Telophase

Upon splitting of the © Jones & Bartlett Learning, LLC © Jones & Bartlettcentromere, Learning, each LLCsister NOT FOR SALE OR DISTRIBUTION NOT FOR SALE ORchromatid DISTRIBUTION becomes a separate chromosome.

FIGURE 4.3 Chromosome behavior during mitosis in an organism with two pairs of chromosomes (red/rose versus green/blue). At each stage, the smaller inner diagram represents the entire cell, and the larger diagram is an exploded view showing the chromosomes at that stage. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.2 Mitosis 121

26105_CH04_116_153.indd 121 4/27/11 9:32 AM (A) Centromere all of the kinetochores are under tension and © Jones & Bartlett Learning, LLC © Jones & alignedBartlett on Learning,the metaphase LLC plate, the metaphase NOT FOR HomologousSALE OR DISTRIBUTION Sister chromatidsNOT FOR SALEcheckpoint OR isDISTRIBUTION passed and the cell continues the chromosomes process of division.

Sister chromatids 3. Anaphase In anaphase, the proteins © Jones & Bartlett Learning, LLC holding the chromatids© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION together are dissolved.NOT FOR SALE OR DISTRIBUTION Homologous chromosomes pair. The centromeres be- Spindle come separate, and the (B) two sister chromatids of each chromo- Pole © Jones & Bartlett Learning, LLC some© Jonesmove &toward Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION oppositeNOT FORpoles SALEof the OR DISTRIBUTION spindle. Once the centromeres separate, each sister chromatid is ANAPHASE of Scadoxus. regarded as a separate [© Andrew S. Bajer/Bajer Research Projects.] © Jones & Bartlett Learning, LLC © Jones & chromosomeBartlett Learning, in its own LLC NOT FOR SALE ORHomologous DISTRIBUTION chromosomes separate. NOT FOR SALEright. Chromosome OR DISTRIBUTION movement results in part from progressive shortening of the spindle fibers (C) attached to the centromeres, which pulls the chromosomes in opposite directions toward the poles, and often also from a temporary elonga- © Jones & Bartlett Learning, LLC tion of the dividing ©cell Jones in a direction & Bartlett paralleling Learning, LLC NOT FOR SALE OR DISTRIBUTION the spindle. At the completionNOT FOR of SALE anaphase, OR the DISTRIBUTION chromosomes lie in two groups near opposite poles of the spindle. Each group contains the same number of chromosomes that was present Daughter nuclei in the original interphase nucleus. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC (D) 4. Telophase In telo- NOT FOR SALE OR DISTRIBUTION phase,NOT a FOR nuclear SALE en- OR DISTRIBUTION velope forms around each compact group of chromosomes, nucle- © Jones & Bartlett Learning, LLC © Jones & oliBartlett are formed, Learning, and the LLC spindle disappears. The NOT FOR SALE OR DISTRIBUTION NOT FOR SALEchromosomes OR DISTRIBUTION undergo a reversal of condensa- Centromeres split and chromatids separate. tion until they are no (E) longer visible as dis- © Jones & Bartlett Learning, LLC crete entities. The ©two Jones & Bartlett Learning, LLC daughter nuclei slowly NOT FOR SALE OR DISTRIBUTION assume a typical inter-NOT FOR SALE OR DISTRIBUTION TELOPHASE of Scadoxus. phase appearance as [© Andrew S. Bajer/Bajer the cytoplasm of the Research Projects.]

NOT FOR SALE OR DISTRIBUTION FIGURENOT 4.4 Overview FOR of SALE the behavior OR of DISTRIBUTIONa single pair of homologous chromosomes in meiosis. The key differences from mitosis are the pairing of homologous chromosomes (A) and the two successive nuclear divisions (B and D) that reduce the chromosome number by half. For clarity, this diagram does not Four daughter nuclei, the products of meiosis incorporate crossing over, an interchange of chromosome © Jones & Bartlett Learning, LLC © Jones segments& Bartlett that takes Learning, place at the stage LLC depicted in part A. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

122 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 122 4/27/11 9:32 AM cell divides into two by means of a gradually so both of the two nuclei that are © Jones deepening& Bartlett furrow Learning, around LLC the periphery. (In © Jonesformed & contain Bartlett a haploid Learning, set of chromo-LLC NOT FORplants, SALE a newOR cellDISTRIBUTION wall is synthesized between NOTsomes. FOR SALE(Chromosomes OR DISTRIBUTION are enumerated the daughter cells and separates them.) by counting the number of centromeres, not the number of chromatids.) Meiosis 3. The second nuclear division loosely re- 4.3 sembles a mitotic division, but there is no Meiosis is the mode ©of cellJones division & Bartlett that results Learning, LLCDNA replication. At metaphase,© Jones the chro- & Bartlett Learning, LLC in haploid daughter NOTcells containing FOR SALE only OR one DISTRIBUTIONmosomes align on the metaphaseNOT FOR plate; SALE OR DISTRIBUTION member of each pair of chromosomes. The pro- and at anaphase, the chromatids of each cess generates genetic diversity because each chromosome are separated into opposite daughter cell contains a different set of alleles. daughter nuclei (Figure 4.4D). The net Meiosis consists of two successive nuclear divi- effect of the two divisions in meiosis is sions.© An Jones overview & ofBartlett the chromosome Learning, behavior LLC the creation© Jonesof four &haploid Bartlett daughter Learning, LLC is outlinedNOT inFOR FIGURE SALE 4.4. OR DISTRIBUTION nuclei, eachNOT containing FOR theSALE equivalent OR DISTRIBUTION of 1. Prior to the first nuclear division, the a single sister chromatid from each pair of members of each pair of homologous homologous chromosomes (Figure 4.4E). chromosomes become closely associated Figure 4.4 does not show that the paired along their length (Figure 4.4). Each homologous chromosomes can exchange genes. © Jones & Bartlettmember Learning, of the pair LLC is already replicated The© exchangesJones & result Bartlett in the Learning, formation of chromo-LLC NOT FOR SALEand OR consists DISTRIBUTION of two sister chromatids somesNOT that FOR consist SALE of segments OR DISTRIBUTION from one homolo- joined at the centromere. The pairing of gous chromosome intermixed with segments the homologous chromosomes therefore from the other. In Figure 4.4, the exchanged produces a four-stranded structure. chromosomes would be depicted as segments of 2. In the first nuclear division, the homolo- alternating color. The exchange process is one of gous chromosomes© Jones are separated & Bartlett from Learning, the critical LLC features of meiosis, and© Jones it will be& Bartlett Learning, LLC each other, theNOT members FOR SALEof each ORpair DISTRIBUTIONexamined in the next section. NOT FOR SALE OR DISTRIBUTION going to opposite poles of the spindle In animals, meiosis takes place in specific (Figure 4.4B). Each daughter chromo- cells called meiocytes, a general term for the pri- some consists of two chromatids attached mary oocytes and spermatocytes in the gamete- to a common centromere (Figure 4.4C), forming tissues (FIGURE 4.5). The oocytes form egg © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONEgg cell NOTThree FOR daughter SALE cells OR DISTRIBUTION degenerate in the n n formation of the egg. n n

n gamete © Jones & Bartlett Learning, LLC ©(sperm) Jones & Bartlett Learning, LLC Fertilization Meiocyte NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 2n (primary oocyte or Mitosis n spermatocyte) n

Diploid Zygote organism

FIGURE 4.5 The life cycle of a typical animal. The number n is the number of chromosomes in the haploid chromosome complement. © Jones &In males,Bartlett the four Learning,products of meiosis LLC develop into functional sperm; in females,© Jones only one & of theBartlett four products Learning, develops into anLLC egg. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.3 Meiosis 123

26105_CH04_116_153.indd 123 4/27/11 9:32 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Microsporocyte NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR (2DISTRIBUTIONn)

Tassel

Meiosis Mature © Jones & Bartlett Learning, LLC © Jones &Megaspores Bartlett Learning, LLC Endosperm sporophyte (2n) (n) NOT FOR SALE OR DISTRIBUTION(3n) NOT FOR SALE OR DISTRIBUTION The endosperm (triploid) results Mitosis Mitosis Surviving from the fusion of two haploid Mature kernel megaspore maternal nuclei and one haploid Polar paternal nucleus. nuclei (n) Embryo Egg © Jones & Bartlett Learning, LLC (2©n) Jones & Bartlettnucleus Learning, LLC Mature (n) Microspore NOT FOR SALE TheOR embryo DISTRIBUTION (diploid)results NOT FORembryo SALE sac OR DISTRIBUTION(n) from the fusion of one haploid maternal nucleus and one haploid paternal Germinated nucleus. pollen Fertilization Sperm grain © Jones & Bartlett Learning, LLC nuclei (n©) Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

FIGURE 4.6 The life cycle of corn, Zea mays. As is typical in higher plants, the diploid spore-producing (sporophyte) generation is conspicuous, whereas the gamete-producing (gametophyte) generation is microscopic. The egg-producing spore is the megaspore, and the sperm-producing spore is the microspore. Nuclei participating in meiosis and fertilization are shown in yellow and green, respectively. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORcells, SALE and ORthe spermatocytesDISTRIBUTION form sperm cells. chromosomesNOT FOR. The SALE nuclear OR divisions—called DISTRIBUTION the Although the process of meiosis is similar in all first meiotic division and the second meiotic division— sexually reproducing organisms, in the female of can be separated into a sequence of stages similar both animals and plants, only one of the four to those used to describe mitosis. The distinctive products develops into a functional cell while the events of this important process occur during the © Jones & Bartlett Learning,other three LLCdisintegrate. In animals, the products© Jones & firstBartlett division Learning, of the nucleus. LLC These events are NOT FOR SALE OR DISTRIBUTIONof meiosis form either sperm or eggs. InNOT plants, FOR SALEdescribed OR in DISTRIBUTIONthe following section. the situation is slightly more complicated: 1. The products of meiosis typically form The First Meiotic Division: Reduction spores, which undergo one or more The first meiotic division (meiosis I) is some- mitotic divisions to produce a haploid times called the reductional division because First © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC nuclear gametophyte organism. The gametophyte it divides the chromosome number in half. By division NOTproduces FOR gametes SALE by OR mitotic DISTRIBUTION division of analogy with mitosis,NOT the FORfirst meiotic SALE division OR DISTRIBUTION a haploid nucleus (FIGURE 4.6). can be split into four stages, which are called 2. Fusion of haploid gametes creates a dip- prophase I, metaphase I, anaphase I, and loid zygote that develops into the sporo- telophase I. These stages are generally more phyte plant, which undergoes meiosis to complex than their counterparts in mitosis. The © Jones & Bartlettproduce Learning, spores and soLLC restarts the cycle. stages© Jones and substages & Bartlett can be Learning, visualized with LLC ref- NOT FOR SALEMeiosis OR is a DISTRIBUTIONmore complex and considerably erenceNOT to FOR FIGURES SALE 4.7 and OR 4.8. DISTRIBUTION longer process than mitosis and usually requires days or even weeks. The entire process of meiosis 1. Prophase I This long stage lasts several FIGURE 4.7 Second is illustrated in its cellular context in . days in most higher organisms. It is commonly nuclear The essence is that meiosis consists of two divisions divided into five substages: leptotene, zygotene, © Jonesdivision & Bartlett Learning,of the nucleus LLC but only one replication© ofJones the & pachyteneBartlett, diploteneLearning,, and LLCdiakinesis. These terms NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

124 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 124 4/27/11 9:32 AM describe the appearance of the chromosomes now clearly double (Figure 4.8E). The pairs © Jones at& eachBartlett substage. Learning, LLC of© homologousJones & Bartlett chromosomes Learning, remain LLC held NOT FOR SALE OR DISTRIBUTIONIn leptotene, which lit- togetherNOT FOR at intervalsSALE OR by DISTRIBUTIONcross-connections erally means “thin thread,” resulting from crossing over. Each cross- the chromosomes first become connection is called a chiasma (plural, chi- visible as long, threadlike asmata) and is formed by a breakage and structures. The pairs of sis- rejoining between nonsister chromatids. Leptotene ter chromatids© Jones can& Bartlett be distin- Learning,As shown LLC in the chromosome and© Jones diagram & Bartlett Learning, LLC guishedNOT by electronFOR SALE microscopy. OR DISTRIBUTIONin FIGURE 4.9, a chiasma results fromNOT physical FOR SALE OR DISTRIBUTION In this initial phase of chromo- exchange between chromatids of homologous some condensation, numer- chromosomes. In normal meiosis, each bivalent ous dense granules appear at usually has at least one chiasma, and biva- irregular intervals along their lents of long chromosomes often have three © Jones &length. Bartlett These Learning, localized contrac- LLC or more chiasmata.© Jones & Bartlett Learning, LLC Zygotene NOT FORtions, SALE called OR chromomeres DISTRIBUTION, have The final periodNOT FOR SALE OR DISTRIBUTION a characteristic number, size, and position in a of prophase I is dia- given chromosome (Figure 4.8A). kinesis, in which the Diakinesis The zygotene period is marked by the lat- homologous chromo- eral pairing, or synapsis, of homologous chro- somes seem to repel © Jones &mosomes, Bartlett beginning Learning, at the LLC chromosome tips. each© Jones other &and Bartlett the Learning, LLC NOT FOR(The SALE term OR zygotene DISTRIBUTION means “paired threads.”) segmentsNOT FOR not SALEconnected OR byDISTRIBUTION chiasmata move As the pairing proceeds in zipper-like fash- apart. (Diakinesis means “moving apart.”) It ion along the length of the chromosomes, it is at this substage of prophase I that the chro- results in a precise chromomere-by-chromo- mosomes attain their maximum condensation. mere association (Figure 4.8B and F). Synapsis The homologous chromosomes in each biva- is facilitated by the synaptonemal© Jones & Bartlett complex Learning,, lent remain LLC connected by at least one© Jones chiasma, & Bartlett Learning, LLC a protein structure thatNOT helps FOR hold SALE the aligned OR DISTRIBUTIONwhich persists until the first meioticNOT anaphase. FOR SALE OR DISTRIBUTION homologous chromosomes together. Each Near the end of diakinesis, the formation of a pair of synapsed homologous chromosomes is spindle is initiated, and the nuclear envelope referred to as a bivalent. breaks down.

© Jones & Bartlett Learning, LLC 2. Metaphase I ©Each Jones biva- & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION lent is maneuveredNOT into FOR a SALE OR DISTRIBUTION Pachytene position straddling the metaphase plate with the centromeres of the homologous Throughout pachytene (Figure 4.8C and D), chromosomes oriented to © Jones &which Bartlett literally Learning, means “thick LLC thread,” the chro- opposite© Jones poles & ofBartlett the spindle Learning, LLC NOT FORmosomes SALE ORcontinue DISTRIBUTION to shorten and thicken (FIGURENOT 4.10A FOR). The SALE orientation OR DISTRIBUTION Metaphase I (Figure 4.7). By late pachytene, it can some- of the centromeres determines which member times be seen that each bivalent (that is, each of each bivalent will subsequently move to set of paired chromosomes) actually consists of each pole, and whether the maternal or the a tetrad of four chromatids, but the two sister paternal centromere is oriented toward a par- chromatids of each chromosome© Jones & areBartlett usually Learning, ticular LLC pole is completely a matter© ofJones chance. & Bartlett Learning, LLC juxtaposed very tightly.NOT Genetic FOR exchangeSALE OR by DISTRIBUTIONAs shown in FIGURE 4.11, the bivalentsNOT formed FOR SALE OR DISTRIBUTION means of crossing over takes place during from nonhomologous pairs of chromosomes pachytene. In Figure 4.7, the sites of exchange can be oriented on the metaphase plate in are indicated by the points where chromatids either of two ways. If each of the nonho- of different colors cross over each other. mologous chromosomes is heterozygous for © Jones & BartlettAt the Learning,onset of diplo- LLC a pair of alleles, ©then Jones one type& Bartlett of alignment Learning, LLC NOT FORtene SALE, the OR synaptonemal DISTRIBUTION com- results in A B andNOT a b FORgametes, SALE whereas OR DISTRIBUTIONthe plex breaks down and the other type results in A b and a B gametes synapsed chromosomes be- (Figure 4.11). Because the metaphase align- gin to separate. Diplotene ment takes place at random, the two types of means “double thread,” and the alignment—and therefore the four types Diplotene © Jones & Bartlett Learning,diplotene LLC chromosomes are of© gametes—are Jones & Bartlett equally frequent.Learning, The LLC ratio of NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.3 Meiosis 125

26105_CH04_116_153.indd 125 4/27/11 9:32 AM FIGURE 4.7 Chromosome behavior during meiosis in an organism with two pairs of homologous chromosomes (red/rose and green/ © Jones & Bartlett Learning,blue). At each stage,LLC the small diagram represents the© entire Jones cell and & the Bartlett larger diagram Learning, is an expanded LLC view of the chromosomes at that stage. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Sister chromatids become visible. Pairing is complete. Synapsis, or Sister homologous chromatids © chromosomeJones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOTpairing, FOR begins. SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Chromosomes first become visible. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Early pachytene © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE ORZygotene DISTRIBUTION NOT FOR SALE OR DISTRIBUTION PROPHASE I (chromosome pairing and condensation; crossing over)

Leptotene © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Telophase II © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning,Anaphase LLC II NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

126 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 126 4/27/11 9:32 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORChromosomes SALE OR become DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Homologous chromosomes shorter and thicker; repel; they are held chiasmata are prominent. together by chiasmata.

Chiasma © Jones & Bartlett Learning, LLC © JonesBivalents & alignBartlett on Learning, LLC NOT FOR SALE OR DISTRIBUTION NOTthe FOR metaphase SALE plate. OR DISTRIBUTION

Bivalent © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Homologous © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC chromosomes separate. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Diplotene Diakinesis

MEIOSIS Anaphase I © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Telophase I

4.3 Meiosis 127

26105_CH04_116_153.indd 127 4/27/11 9:32 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

(A) Leptotene (B) Zygotene (C) Early pachytene © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

(D) Late pachytene (E) Diplotene (F) Detail of synapsis FIGURE 4.8 Substages of prophase I in microsporocytes of the lily (Lilium longiflorum). (A) Leptotene: condensation of the chromosomes is initiated and beadlike chromomeres© are Jones visible along & theBartlett length of the Learning, chromosomes. LLC (B) Zygotene: pairing (synapsis) of homologous© Jones chromo & Bartlettsomes occurs Learning, LLC (paired and unpaired regions can be seen particularly at the lower left in this photograph). (C) Early pachytene: synapsis is completed and crossing over between homologous NOTchromosomes FOR occurs. SALE (D) LateOR pachytene: DISTRIBUTION continuation of the shortening and thickeningNOT of the FOR chromosome SALEs. (E) OR Diplo- DISTRIBUTION tene: mutual repulsion of the paired homologous chromosomes, which remain held together at one or more cross points (chiasmata) along their length. Diakinesis follows (not shown): the chromosomes reach their maximum contraction. (F) Zygotene (at higher magnification in another cell) showing paired homologs and matching of chromomeres during synapsis. [Parts A, B, C, E, and F courtesy of Marta Walters and Santa Barbara Botanic Gardens, Santa Barbara, California. Part D courtesy of Herbert Stern. Used with permission of Ruth Stern.] © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (A) (B) Centromere Chromatid

NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Chiasma

Centromere FIGURE 4.9© JonesLight micrograph & Bartlett (A) and interpretive Learning, drawing LLC (B) of a bivalent consisting of a pair of© homologous Jones chromosomes.& Bartlett This Learning, LLC bivalent was photographed at late diplotene in a spermatocyte of the salamander Oedipina poelzi. It shows two chiasmata where the chromatidsNOT of the FOR homologous SALE chromosomes OR DISTRIBUTION appear to exchange pairing partners. [ReproducedNOT from The FOR Mechanics SALE of Inheritance OR DISTRIBUTION by Franklin W. Stahl. Copyright © 1964 by Prentice-Hall, Inc. Reprinted by permission of Pearson Education, Inc.]

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORthe SALE four types OR DISTRIBUTION of gametes is 1 : 1 : 1 : 1, which 3. NOTAnaphase FOR I SALEIn this ORstage, DISTRIBUTION means that the A, a and B, b pairs of alleles homologous chromosomes, undergo independent assortment. That is, each composed of two chro- Genes on different chromosomes undergo matids joined at an undi- independent assortment because nonhomolo- vided centromere, separate © Jones & Bartlett Learning,gous chromosomes LLC align at random on© the Jones & fromBartlett one anotherLearning, and moveLLC NOT FOR SALE OR DISTRIBUTIONmetaphase plate in meiosis I. NOT FOR SALEto opposite OR DISTRIBUTION poles of the Anaphase I

128 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 128 4/27/11 9:32 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

(A) Metaphase I © Jones & Bartlett(B) Anaphase Learning, I LLC (C) Metaphase II (telophase© Jones I and propase & Bartlett II Learning, LLC NOT FOR SALE OR DISTRIBUTION not shown) NOT FOR SALE OR DISTRIBUTION

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION FIGURE 4.10 Later meiotic stages in microsporocytes of the lily Lilium longiflorum: (A) metaphase I; (B) anaphase I; (C) metaphase II; (D)˛anaphase II; (E) telophase II. Cell walls have begun to © Jones &form Bartlett in telophase, Learning, which will lead LLCto the © Jones & Bartlett Learning, LLC NOT FORformation SALE of ORfour pollen DISTRIBUTION grains. [Courtesy NOT FOR SALE OR DISTRIBUTION of Herbert Stern. Used with permission of Ruth Stern.] (D) Anaphase II (E) Telophase II

A B A b A B or A b © Jones & Bartlett Learning,a LLC b © Jones & Bartletta Learning,B LLC NOT FOR SALE OR DISTRIBUTIONa b NOT FOR SALEa OR DISTRIBUTIONB

The gametes produced from this alignment are The gametes produced from this alignment are A B : A B : a b : a b A b : A b : a B : a B © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE BecauseOR DISTRIBUTION the alignments are equally likely, the overallNOT FOR SALE OR DISTRIBUTION ratio of gametes is A B : A b : a B : a b = 1 : 1 : 1 : 1 This ratio is characteristic of independent assortment. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC FIGURE 4.11 Independent assortment of genes (A or B) on nonhomologous chromosomes results from random alignment of NOT FORnonhomologous SALE OR chromosomes DISTRIBUTION at metaphase I. NOT FOR SALE OR DISTRIBUTION

4.3 Meiosis 129

26105_CH04_116_153.indd 129 4/27/11 9:32 AM connection © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORGrasshopper, SALE OR DISTRIBUTION Grasshopper NOT FOR SALE OR DISTRIBUTION

As an undergraduate researcher, Caroth- the primary spermatocytes of certain twelve separate individuals [the biva- ers showed that nonhomologous chromo- grasshoppers. The distribution of the lents]. Side views show the X chromo- ©somes Jones undergo & Bartlett chromosomes Learning, of this LLC bivalent, in rela- some in its© characteristicJones & Bartlett position nearLearning, LLC E. Eleanor Carothers 1913 independent tion to the X chromosome, follows the one pole. . . . Three hundred cells were University of Kansas, NOTassortment FOR SALEin laws OR of chance;DISTRIBUTION and, therefore, affords drawn underNOT FORthe camera SALE lucida OR DISTRIBUTIONto Lawrence, Kansas meiosis. For this direct cytological support of Mendel’s determine the distribution of the The Mendelian Ratio in purpose she laws. This distribution is easily traced chromosomes in the asymmetrical Relation to Certain studied a grass- on account of a very distinct difference bivalent in relation to the X chromo- Orthopteran© Chromosomes Jones & Bartletthopper inLearning, which in sizeLLC of the homologous chromo-© Jonessome. & Bartlett. . . In the Learning,300 cells drawn, LLC the one pair of ho- somes. Thus another link is added to smaller chromosome went to the same mologousNOT chromosomes FOR SALE had ORmembers DISTRIBUTION of the already long chain of NOT FOR SALE ORnucleus DISTRIBUTION as the X chro- unequal length. At the first anaphase evidence that the chro- Another link is added mosome 146 times, or in of meiosis in males, she could determine by mosomes are distinct to the already long 48.7 percent of the cases; observation whether the longer or the shorter morphological individu- chain of evidence that and the larger one, 154 © Jones &chromosome Bartlett went Learning, in the same LLC direction as als continuous from© Jones gen- &the Bartlett chromosomes Learning, are LLCtimes, or in 51.3 percent the X chromosome. As detailed in this paper, eration to generation, of the cases. . . . A con- NOT FOR SALE OR DISTRIBUTION NOT FOR distinctSALE morphologicalOR DISTRIBUTION she found 154 of the former and 146 of the and, as such, are the individuals continuous sideration of the limited latter, a result in very close agreement with bearers of the hereditary from generation to number of chromo- the 1 : 1 ratio expected from independent qualities. . . . This work is generation, and, as somes and the large assortment. There is no mention of the based chiefly on Brachy- such, are the bearers of number of characters in Y chromosome because in the grasshopper stola magna [a short- any animal or plant will © Jones & Bartlett Learning, LLC the hereditary © Jones & Bartlett Learning, LLC she studied, the females have the sex chromo- horned grasshopper]. . . . make it evident that NOT FOR SALE OR DISTRIBUTION qualities. NOT FOR SALE OR DISTRIBUTION some constitution XX, whereas the males The entire complex of each chromo some must have the sex chromosome constitution X. In chromosomes can be control numerous dif- the males she examined, therefore, the separated into two groups, one con- ferent characters. . . . Since the redis- X chromosome did not have a pairing part- taining six small chromosomes and the covery of Mendel’s laws, increased ner. The© Jonesinstrument & referred Bartlett to as aLearning, camera other LLC seventeen larger ones. [One© Jones of knowledge & Bartlett has been Learning, constantly LLC bring- lucidaNOT was at FORthat time SALE in widespread OR DISTRIBUTION use for the larger ones is the X chromosome.]NOT FORing into SALE line factsOR thatDISTRIBUTION at first seemed studying chromosomes and other microscopic Examination shows that this group of utterly incompatible with them. There objects. It is an optical instrument containing six small chromosomes is composed of is no cytological explanation of any a prism or an arrangement of mirrors that, five of about equal size and one decid- other form of inheritance. . . . It seems when mounted on a microscope, reflects an edly larger. [One of the small ones is to me probable that all inheritance is, © Jones &image Bartlett of the microscopic Learning, object onto LLC a piece of the homolog of© the Jones decidedly & Bartlett larger Learning,in reality, Mendelian. LLC paper where it can be traced. one, making this pair of chromosomes NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION The aim of this paper is to describe unequal in size.] . . . In early meta- Source: E. E. Carothers, J. Morphol. 24 (1913): the behavior of an unequal bivalent in phases the chromosomes appear as 487–511.

spindle© (Figure Jones 4.10B). & Bartlett Chromosome Learning, separa- LLC persists throughout© meiosis Jones I. It & disappears Bartlett only Learning, LLC tion atNOT anaphase FOR isSALE the cellular OR DISTRIBUTION basis of the at anaphase II, whenNOT sister-centromere FOR SALE OR cohe- DISTRIBUTION segregation of alleles: sion is lost and the sister centromeres separate.

The physical separation of homologous chro- 4. Telophase I At the mosomes in anaphase is the physical basis of completion of ana- Mendel’s principle of segregation. © Jones & Bartlett Learning, LLC phase© Jones I, a haploid & Bartlett set Learning, LLC of chromosomes con- NOT FORNote, SALE however, OR DISTRIBUTION that the centromeres of the NOT FOR SALE OR DISTRIBUTION sister chromatids are tightly stuck together and sisting of one homolog behave as a single unit. A specific protein acts as from each bivalent is a glue holding the sister centromeres together. located near each pole This protein appears in the centromeres and of the spindle (Fig- © Jones & Bartlett Learning,adjacent chromosome LLC arms during S phase© Jones and & ureBartlett 4.6). In Learning, telophase, LLC Telophase I NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

130 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 130 4/27/11 9:32 AM the spindle breaks down, and, depending on resembles a mitotic division. However, there is © Jones the& Bartlett species, eitherLearning, a nuclear LLC envelope briefly an© important Jones & difference: Bartlett Learning, LLC forms around each group of chromosomes or NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION The chromatids of a chromosome are usu- the chromosomes enter the second meiotic ally not genetically identical along their entire division after only a limited uncoiling. length because of crossing over associated with the formation of chiasmata during prophase of the first division. The Second Meiotic© Division:Jones Equation& Bartlett Learning, LLC © Jones & Bartlett Learning, LLC The second meioticNOT division FOR (meiosis SALE ORII) is DISTRIBUTION NOT FOR SALE OR DISTRIBUTION sometimes called the equational division 4.4 Sex-Chromosome Inheritance because the chromosome number remains the The first rigorous experimental proof that genes same in each cell before and after the second are parts of chromosomes was obtained in division. In some species, the chromosomes pass experiments concerned with the pattern of directly from telophase I to prophase II with- © Jones & Bartlett Learning, LLC transmission of the© Jonessex chromosomes & Bartlett ,Learning, the LLC out lossNOT of FORcondensation; SALE OR in others, DISTRIBUTION there is a NOT FOR SALE OR DISTRIBUTION brief pause between the two meiotic divisions chromosomes responsible for determination of and the chromosomes may “decondense” the separate sexes in some plants and in nearly (uncoil) somewhat. Chromosome replication never all animals. We will examine these results in this takes place between the two divisions; the chromo- section. © Jones &somes Bartlett present Learning, at the beginning LLC of the second © Jones & Bartlett Learning, LLC Chromosomal Determination of Sex NOT FORdivision SALE are OR identical DISTRIBUTION to those present at the end NOT FOR SALE OR DISTRIBUTION of the first. The sex chromosomes are an exception to After a short prophase (prophase II) and the the rule that all chromosomes of diploid organ- formation of second-division spindles, the cen- isms are present in pairs of morphologically tromeres of the chromosomes in each nucleus similar homologs. As early as 1891, microscopic become aligned on the© central Jones plane & Bartlett of the spin- Learning,analysis LLC had shown that one of the© Jones chromo- & Bartlett Learning, LLC dle at metaphase IINOT (Figure FOR 4.10C). SALE In ana-OR DISTRIBUTIONsomes in males of some insect speciesNOT does FOR not SALE OR DISTRIBUTION phase II the protein holding the sister have a homolog. This unpaired chromosome centromeres to- was called the X chromosome, and it was pres- gether breaks down. ent in all somatic cells of the males but in only As a result, the sister half the sperm cells. The biological significance © Jones & Bartlettcentromeres Learning, LLCap- of these observations© Jones became & Bartlett clear when Learning, LLC NOT FOR SALE ORpear DISTRIBUTION to split longitu- females of the sameNOT species FOR were SALE shown OR to have DISTRIBUTION dinally, and the two X chromosomes. chromatids of each In other species in which the females have two X chromosomes, the male has one X chro- Metaphase II chromosome move to opposite poles of mosome along with a morphologically © Jones & Bartlett Learning, LLCthe spindle (Fig- unmatched© Jones &chromosome. Bartlett Learning, The unmatched LLC chromosome is referred to as the Y chromo- NOT FOR SALE OR DISTRIBUTIONure 4.10D). Once the NOT FOR SALE OR DISTRIBUTION centromeres split at some, and it pairs with the X chromosome anaphase II, each during meiosis in males, usually along only chromatid is consid- part of its length because of a limited region of Anaphase II ered to be a separate homology. The difference in chromosomal © Joneschromosome. & Bartlett Learning,constitution LLC between males and ©females Jones is &a Bartlett Learning, LLC chromosomal mechanism for determining sex NOT FORTelophase SALE OR II DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (Figure 4.10E) is at the time of fertilization. Whereas every egg marked by a transi- cell contains an X chromosome, half of the tion to the inter- sperm cells contain an X chromosome and the phase condition of rest contain a Y chromosome. Fertilization of © Jones & Bartlettthe Learning, chromosomes LLC in an X-bearing egg© Jonesby an X-bearing& Bartlett sperm Learning, LLC NOT FOR SALE ORthe DISTRIBUTIONfour haploid results in an XX zygote,NOT FORwhich SALE normally OR devel- DISTRIBUTION nuclei, accompanied ops into a female; and fertilization by a by division of the Y-bearing sperm results in an XY zygote, which cytoplasm. Thus, the normally develops into a male (FIGURE 4.12). The second meiotic divi- result is a criss-cross pattern of inheritance of © Jones & Bartlett Learning,Telophase II LLCsion superficially the© JonesX chromosome & Bartlett in which Learning, a male receivesLLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.4 Sex-Chromosome Inheritance 131

26105_CH04_116_153.indd 131 4/27/11 9:32 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© Jones & BartlettXX Learning, LLC ©XY Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Female (&) The result of Male (() meiosis is one Meiosis type of egg and two types © Jones & Bartlett Learning, LLC of sperm. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

X © Jones & Bartlett Learning, LLCX © JonesX & Bartlett Learning, LLC Y NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Eggs Sperm

Fertilization

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Sex of the progeny is determined by the sex Progeny chromosome contained in the sperm.

FIGURE 4.12 The chromosomal basis of sex determination in mammals, many insects, and other animals.

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONhis X chromosome from his mother andNOT trans- FOR SALEThe OR X and DISTRIBUTION Y chromosomes together consti- mits it only to his daughters. tute the sex chromosomes; this term distin- The XX–XY type of chromosomal sex deter- guishes them from other pairs of chromosomes, mination is found in mammals, including which are called autosomes. Although the sex human beings, in many insects, and in other chromosomes control the developmental switch animals,© Jonesas well as& inBartlett some flowering Learning, plants. LLC that determines the© earliest Jones stages & Bartlett of female Learning, or LLC The femaleNOT isFOR called SALE the homogameticOR DISTRIBUTION sex male development,NOT the developmental FOR SALE processOR DISTRIBUTION because only one type of gamete (X-bearing) is itself requires many genes scattered throughout produced, and the male is called the heteroga- the genome, including genes on the autosomes. metic sex because two different types of gam- The X chromosome also contains many genes © Jonesetes & Bartlett (X-bearing Learning, and Y-bearing) LLC are produced. with© Jonesfunctions & unrelated Bartlett to Learning, sexual differentia- LLC When the union of gametes in fertilization is tion, as we will see in the next section. In most NOT FORrandom, SALE a OR sex DISTRIBUTIONratio at fertilization of 1 : 1 is organisms,NOT FOR including SALE human OR DISTRIBUTIONbeings, the Y chro- expected because males produce equal numbers mosome carries few genes other than those of X-bearing and Y-bearing sperm. related to male determination.

132 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 132 4/27/11 9:32 AM (A) (B) © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

© JonesMale & (( )Bartlett Learning,Female LLC (&) Red eyes© JonesWhite & Bartlett eyes Learning, LLC FIGURENOT 4.13 DrawingsFOR SALE (A) of a male OR and DISTRIBUTION a female fruit fly, Drosophila melanogaster. The photographsNOT FOR (B) show SALE the eyes OR of aDISTRIBUTION wildtype red-eyed male and a mutant white-eyed male. [Illustrations © Carolina Biological Supply Company. Used with permission. Photographs courtesy of E. R. Lozovsky.]

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEX-Linked OR Inheritance DISTRIBUTION NOT FOR SALE OR DISTRIBUTION The compelling evidence that genes are located in chromosomes came from the study of a Drosophila gene for white eyes, which proved to be present© in Jones the X chromosome.& Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Recall that in Mendel’s crosses, it did not matter which trait was presentNOT in the FOR male SALE parent OR and DISTRIBUTION NOT FOR SALE OR DISTRIBUTION which in the female parent. Reciprocal crosses gave the same result. One of the earliest exceptions to this rule was found by Thomas Hunt Morgan© Jones in 1910 & in Bartlett an early studyLearning, of a mutant LLC © Jones & Bartlett Learning, LLC fruit fly that had white eyes. The wildtype eye colorNOT is a brick-redFOR SALE combination OR DISTRIBUTION of red and NOT FOR SALE OR DISTRIBUTION brown pigments (FIGURE 4.13). Although white eyes can result from certain combinations of autosomal genes that eliminate the pigments individually, the white-eye mutation that Mor- © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC gan studied results in a metabolic block that MORGAN’S GROUP partying in the fly room at Columbia University in 1919, to NOT FORknocks SALE out OR both DISTRIBUTION pigments simultaneously. (The celebrateNOT A.FOR H. Sturtevant’s SALE return OR fromDISTRIBUTION military service in World War I. T. H. Morgan gene codes for a transmembrane protein that is is on the far right in the back row, with H. J. Muller beside him. Sturtevant is in the necessary to transport the eye pigment precur- foreground, leaning back in his chair, and C. B. Bridges is in shirtsleeves sitting next to an apelike creature dubbed “Pithecanthropus,” a dummy made up for the sors into the pigment cells.) occasion. [Courtesy of the Archives, California Institute of Technology.] Morgan’s study started© Jones with & a singleBartlett male Learning, LLC © Jones & Bartlett Learning, LLC with white eyes that appeared in a wildtype laboratory populationNOT that had FOR been SALE maintained OR DISTRIBUTIONsomehow connected with sex, becauseNOT all FOR of the SALE OR DISTRIBUTION for many generations. In a mating of this male white-eyed flies were males. with wildtype females, all of the F1 progeny of On the other hand, white eyes were not both sexes had red eyes, which showed that the restricted to males. For example, when red-eyed & allele for white eyes is recessive. In the F2 prog- F1 females from the cross of wildtype white © Jones & Bartlett Learning, LLC ( © Jones & Bartlett Learning, LLC eny from the mating of F1 males with females, were backcrossed with their white-eyed MorganNOT observed FOR SALE2459 red-eyed OR DISTRIBUTION females, 1011 fathers, the progenyNOT consisted FOR SALEof both red-eyedOR DISTRIBUTION red-eyed males, and 782 white-eyed males. It and white-eyed females and red-eyed and white- was clear that the white-eyed phenotype was eyed males in approximately equal numbers.

4.4 Sex-Chromosome Inheritance 133

26105_CH04_116_153.indd 133 4/27/11 9:32 AM Male wildtype male as w Y. Because the w allele is © Jones & Bartlett Learning, LLC © Jones & recessive,Bartlett white-eyed Learning, females LLC are of genotype ww NOT FOR SALE OR DISTRIBUTION NOT FOR SALEand wildtype OR DISTRIBUTION females are either heterozygous ww or homozygous ww. The implications of X this model for reciprocal crosses are shown in FIG- URE 4.15. The mating wildtype & white ( is Cross A, and that of white & wildtype ( is © JonesY & Bartlett Learning, LLC Cross B. © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION The X-linked NOTmode FORof inheritance SALE OR does DISTRIBUTION account for the different phenotypic ratios observed in the F1 and F2 progeny from the crosses. The characteristics of X-linked inheritance can be summarized as follows: © Jones & BartlettFemale Learning, LLC ©1. Jones Reciprocal & Bartlett crosses resultingLearning, in LLCdiffer- NOT FOR SALE OR DISTRIBUTION NOTent FOR phenotypic SALE ratios OR DISTRIBUTIONin the sexes often indicate X-linked inheritance. In the case of white eyes in Drosophila, the X cross of a red-eyed female with a white- eyed male yields all red-eyed progeny © Jones & Bartlett Learning, LLC © Jones & Bartlett(Figure Learning, 4.15, Cross LLC A), whereas the X NOT FOR SALE OR DISTRIBUTION NOT FOR SALE crossOR DISTRIBUTIONof a white-eyed female with a red-eyed male yields red-eyed female progeny and white-eyed male progeny FIGURE 4.14 The diploid chromosome complements of a (Figure 4.15, Cross B). male and a female Drosophila melanogaster. The centromere 2. Heterozygous females transmit each of the X ©chromosome Jones is& nearly Bartlett terminal, Learning,but that of the LLC © Jones & Bartlett Learning, LLC Y chromosome divides the chromosome into two unequal X-linked allele to approximately half of arms. TheNOT large autosomesFOR SALE (chromosomes OR DISTRIBUTION 2 and 3, shown their daughtersNOT and FOR half SALE of their OR sons; DISTRIBUTION in blue and green) are not easily distinguishable in these this is illustrated in the F2 generation of types of cells. The tiny autosome (chromosome 4, shown in Cross B in Figure 4.15. yellow) appears as a dot. 3. Males that inherit an X-linked recessive © Jones & Bartlett Learning, LLC © Jonesallele exhibit & Bartlett the recessive Learning, trait becauseLLC NOT FOR SALE OR DISTRIBUTION NOTthe FOR Y chromosome SALE OR DISTRIBUTIONdoes not contain a wildtype counterpart of the gene. Affected males transmit the recessive A key observation came from the mating of allele to all of their daughters but none white-eyed females with wildtype males. All the of their sons; this principle is illustrated female progeny had wildtype eyes, but all the © Jones & Bartlett Learning, LLC © Jones & Bartlettin the Learning, F1 generation LLC of Cross A in Fig- male progeny had white eyes. This is the recip- ure 4.15. Any male that is not affected NOT FOR SALE OR DISTRIBUTIONrocal of the original cross of wildtypeNOT FOR SALE mustOR DISTRIBUTIONcarry the wildtype allele in his X & ( white , which had given only wildtype chromosome. females and wildtype males, so the reciprocal The essence of X-linked inheritance is captured crosses gave different results. in the Punnett square in FIGURE 4.16: A male trans- Morgan realized that reciprocal crosses © Jones & Bartlett Learning, LLC mits his X chromosome© Jones only to& hisBartlett daughters, Learning, LLC would yield different results if the allele for whereas a female transmits an X chromosome to white eyesNOT were FOR present SALE in the OR X chromosome. DISTRIBUTION A offspring of both sexes.NOT FOR SALE OR DISTRIBUTION gene on the X chromosome is said to be X-linked. The normal chromosome complement of Drosophila melanogaster is shown in FIG- Pedigree Characteristics of Human X-Linked URE 4.14. Females have an XX chromosome Inheritance © Jonescomplement, & Bartlett Learning,whereas males LLC are XY. Morgan’s ©An Jones example & Bartlett of a human Learning, trait with LLC an NOT FORhypothesis SALE OR was DISTRIBUTIONthat an X chromosome contains X-linkedNOT FORpattern SALE of inheritance OR DISTRIBUTION is hemophilia A, a either a wildtype w allele or a mutant w allele severe disorder of blood clotting determined by and that the Y chromosome does not contain a a recessive allele. Affected persons lack a blood- counterpart of the white gene. Using the white clotting protein called factor VIII that is needed allele present in an X chromosome to represent for normal clotting, and they suffer excessive, © Jones & Bartlett Learning,the entire X LLC chromosome, we can write the© geno-Jones & oftenBartlett life-threatening Learning, bleeding LLC after injury. A NOT FOR SALE OR DISTRIBUTIONtype of a white-eyed male as wY and thatNOT of FORa SALEfamous ORpedigree DISTRIBUTION of hemophilia starts with Queen 134 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 134 4/27/11 9:32 AM Cross A Cross B © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Parents: NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Red-eyed White-eyed White-eyed Red-eyed female (XX) male (XY) female (XX) male (XY) +w ן w w ן +w w+ © Jones & Bartlett Learning, LLC w © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

F1 : w+ w+ w w © Jones & wBartlett Learning, LLC © Jonesw+ & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Red-eyed females Red-eyed females and males and white-eyed males

Mating F1 progeny Mating F1 progeny F : © Jones & 2Bartlett Learning, LLC © Jones & Bartlett Learning, LLC

NOT FOR SALE OR DISTRIBUTION1 NOT FOR SALE OR DISTRIBUTION1 1/4 Red-eyed /4 Red-eyed 1/4 Red-eyed /4 Red-eyed females males females males w+ w+ w+ w+ w+ w © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 1 1 /4 Red-eyed 1/4 White-eyed /4 White-eyed 1/4 White-eyed females males females males w+ w w w © Jones & wBartlett Learning, LLC © Jonesw & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

FIGURE 4.15 Chromosomal interpretation of the results obtained in F1 and F2 progenies in crosses of Drosophila. Cross A is a mating of a wildtype (red-eyed) female with a white-eyed male. Cross B is the reciprocal mating of a white-eyed female with a red-eyed male. In the X chromosome, the wildtype w+ allele is shown in red, the mutant w allele in white. The Y chromosome does not carry either allele of the w gene.

,XY Learning, LLC Sperm Victoria© Jones of England & Bartlett (FIGURE 4.17Learning,). One of herLLC sons ןJones &XX Bartlett © X Y NOT FOR(& SALE) OR(( )DISTRIBUTION Leopold,NOT FOR was hemophilic, SALE OR and DISTRIBUTION two of her daughters were heterozygous carriers of the gene. Two of Victoria’s granddaughters were also carriers, X &( and by marriage they introduced the gene into XX XY the royal families of Russia and Spain. The heir Eggs© Jones & Bartlett Learning,to the RussianLLC throne of the Romanoffs,© Jones Tsarev- & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTIONich Alexis, was afflicted with the condition.NOT FOR He SALE OR DISTRIBUTION X & ( inherited the gene from his mother, the Tsarina XX XY Alexandra, one of Victoria’s granddaughters. The Tsar, the Tsarina, Alexis, and his four sisters were The female (&) to male (() all executed by the Russian Bolsheviks in the © Jones & Bartlett Learning,ratio is 1:1. LLC 1918 revolution.© Ironically, Jones &the Bartlett present Learning,royal LLC NOT FOR SALE OR DISTRIBUTION family of EnglandNOT is descended FOR SALE from aOR normal DISTRIBUTION FIGURE 4.16 In chromosomal sex determination, each son gets his X chromosome from his mother and his Y chromosome from son of Victoria and is free of the disease. his father. X-linked inheritance in human pedigrees shows several characteristics that distinguish it from other modes of genetic transmission. © Jones & Bartlett Learning, LLC © 1.Jones For any & Bartlettrare trait Learning,due to an X-linkedLLC NOT FOR SALE OR DISTRIBUTION NOTrecessive FOR SALE allele, OR the DISTRIBUTIONaffected individuals

4.4 Sex-Chromosome Inheritance 135

26105_CH04_116_153.indd 135 4/27/11 9:32 AM Queen Victoria of England Prince Albert © Jones & Bartlett Learning,(1819–1901) LLC (1819–1861)© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION Princess Victoria Alice Helena Arthur Beatrice (1840–1901) (1843–1878) (1846–1923) (1850–1942) (1857–1944) Edward VII Alfred Leopold King of England Duke© Jonesof Edinburgh & BartlettLouise Learning, LLCDuke of Albany © Jones & Bartlett Learning, LLC (1841–1910) (1844–1900) (1848–1939) (1853–1884) NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

King George V© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC (1865–1936) NOT FOR SALE OR DISTRIBUTION NicholasNOT II FOR SALE OR DISTRIBUTION Alexandra,Tsarina of Russia Tsar of Russia (1872–1918) (1868–1918) King George VI FIGURE 4.17 Genetic transmission of (1895–1952) hemophilia A among the descendants of Queen Victoria of England, including her © Jones & Bartlett Learning, LLC Olga ©Marie Jones & AlexisBartlett Learning,granddaughter LLC, Tsarina Alexandra of Russia, NOT FORQueen SALE OR DISTRIBUTION (1895–1918) (1899–1918)NOT FOR(1904–1918) SALE OR DISTRIBUTIONand Alexandra’s five children. The photograph Elizabeth II Tatiana Anastasia is that of Tsar Nicholas II, Tsarina Alexandra, (1926–) (1897–1918) (1901–1918) and their children. Tsarevich Alexis was afflicted with hemophilia. [Source: Culver Pictures. Photo courtesy of the Boston Public Carrier female Hemophilic male Died at birth, sex unrecorded Library, Print Department.] © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOTare exclusively, FOR SALE or ORalmost DISTRIBUTION exclusively, 3. A woman whoseNOT FORfather SALE was affected OR DISTRIBUTION male. There is an excess of males because has normal sons and affected sons in females carrying the rare X-linked the ratio 1 : 1. This is true because any recessive are almost exclusively het- daughter of an affected male must be erozygous and so do not express the heterozygous for the recessive allele. © Jones & Bartlettmutant Learning, phenotype. LLC © Jones & Bartlett Learning, LLC NOT FOR SALE2. Affected OR DISTRIBUTIONmales who reproduce have NOTHeterogametic FOR SALE Females OR DISTRIBUTION normal sons. This follows from the fact In some organisms, the homogametic and that a male transmits his X chromosome heterogametic sexes are reversed; that is, the only to his daughters. males are XX and the females are XY. This type of sex determination is found in birds, in some © Jones & Bartlett Learning, LLC © Jones & reptilesBartlett and Learning, fish, and in LLC moths and butterflies. NOT FOR SALE OR DISTRIBUTION NOT FOR SALEThe reversal OR DISTRIBUTIONof XX and XY in the sexes results in (A) (B) an opposite pattern of nonreciprocal inheritance of X-linked genes. To distinguish sex determination in these organisms from the usual XX–XY mechanism, the sex chromosome constitution in © Jones & Bartlett Learning, LLC the homogametic sex© Jonesis designated & Bartlett ZZ and thatLearning, LLC NOT FOR SALE OR DISTRIBUTION in the heterogameticNOT sex as FOR WZ. Hence SALE in ORorgan- DISTRIBUTION isms with heterogametic females, the chromo- ) Barred ן & Nonbarred ( Nonbarred ן & Barred (WZ) (ZZ) (WZ) (ZZ) somal constitution of the females is designated WZ and that of the male ZZ. A specific example of Z-linked inheritance in © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC Nonbarred && and Barred (( Barred && and Barred (( chickens is shown in FIGURE 4.18. A few breeds of (WZ) NOT FOR(Z ZSALE) OR DISTRIBUTION(WZ) (ZZ) chickensNOT FOR have SALE feathers OR DISTRIBUTIONwith alternating

FIGURE 4.18 Barred feathers in chickens, a classic example showing that chromosomal sex determination in birds is © Jones & Bartlett Learning, LLC © Jones & theBartlett reverse of Learning,that in mammals. LLC In birds, females are the heterogametic sex. The Z chromosome carrying the dominant NOT FOR SALE OR DISTRIBUTION NOT FOR SALEbarred mutation OR DISTRIBUTIONis indicated in red.

136 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 136 4/27/11 9:32 AM connection © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORThe SALE White-Eyed OR DISTRIBUTION Male

Morgan’s genetic analysis of the white- year through a considerable number equal numbers (25 percent). . . . The eye mutation marks the beginning of of generations, a male appeared with results just described can be ©Drosophila Jones & Bartlettwhite eyes.Learning, The normal LLC flies have bril- accounted© Jones for by & the Bartlett following Learning, LLC Thomas Hunt Morgan 1910 NOTgenetics. FOR It is SALEin liant OR red DISTRIBUTION eyes. The white-eyed male, hypothesis.NOT Assume FOR SALEthat all OR of the DISTRIBUTION Columbia University, the nature of sci- bred to his red-eyed sisters, produced spermatozoa of the white-eyed male New York, New York ence that as 1,237 red-eyed offspring. . . . The F1 carry the “factor” for white eyes Sex-Limited Inheritance in knowledge in- hybrids, inbred, produced “W”; that half of the spermatozoa Drosophila creases, the terms carry a sex factor “X,” [and] the 2,459 red-eyed females used to describe other half lack it, i.e., the male is het- © Jones & Bartlett Learning, LLC 1,011 red-eyed males © Jones & Bartlett Learning, LLC things change also. This paper affords an erozygous for sex. [The male is actu- NOT FOR SALE OR DISTRIBUTION 782 white-eyed malesNOT FOR SALE OR DISTRIBUTION example, because the term sex-limited ally XY.] Thus, the symbol for the inheritance is used today to mean some- No white-eyed females appeared. male is “WXY”, and for his two kinds thing completely different from Morgan’s The new character showed itself to of spermatozoa WX—Y. Assume that usage. What Morgan was referring to is be sex-linked in the sense that it was all of the eggs of the red-eyed female © Jones &now Bartlett called X-linked Learning, inheritance LLC or sex- transmitted only© Jonesto the grandsons. & Bartlett carryLearning, the red-eyed LLC “factor” R; and NOT FORlinked SALE inheritance. OR DISTRIBUTION To avoid confusion, we But that the characterNOT FOR SALE OR DISTRIBUTIONthat all of the eggs have taken the liberty of substituting the is not incompatible No white-eyed (after meiosis) carry modern equivalent wherever appropriate. with femaleness is females appeared. one X each, the symbol Morgan was also unaware that Drosoph- shown by the following for the red-eyed female ila males had a Y chromosome. He thought experiment. The white-eyed male will be therefore RRXX and that for that females were XX and© malesJones X, as& in Bartlett (mutant) Learning, was later LLC crossed with her eggs ©will Jones be RX. &. . Bartlett. The hypoth- Learning, LLC grasshoppers (see the CarothersNOT paper). FOR WeSALE some OR of DISTRIBUTION his daughters (F1), and esis justNOT utilized FOR to SALEexplain OR these DISTRIBUTION have also supplied the missing Y chromo- produced results first obtained can be tested in some. On the other hand, Morgan’s gene several ways. [There follow four 129 red-eyed females symbols have been retained as in the origi- types of crosses, each yielding the 132 red-eyed males nal. He uses R for the wildtype allele for red expected result.] . . . In order to 88 white-eyed females eyes and© JonesW for the &recessive Bartlett allele forLearning, white LLC © Jonesobtain & Bartlett these results Learning, it is necessary LLC to 86 white-eyed males eyes. ThisNOT is aFOR curious SALE departure OR from DISTRIBUTION the NOT FORassume SALE that, ORwhen DISTRIBUTION the two classes of convention, already introduced by Mendel, The results show that the new spermatozoa are formed in the RXY that dominant and recessive alleles should be character, white eyes, can be carried male, R and X go together. . . . The represented by the same symbol. Today we over to the females by a suitable fact is that this R and X are com- use w for the recessive allele and w for the cross, and is in consequence in this bined and have never existed apart. © Jones &dominant Bartlett allele. Learning, LLC sense not limited© Jones to one sex.& Bartlett It will Learning, LLC NOT FOR SALEIn a pedigree OR DISTRIBUTION culture of Drosophila be noted thatNOT the fourFOR classes SALE of OR Source: DISTRIBUTION T. H. Morgan, Science 32 (1910): that had been running for nearly a individuals occur in approximately 120–122.

transverse bands of light and dark color, resulting parts of chromosomes. Other experiments with in a phenotype known© as Jones barred. In& otherBartlett breeds Learning, Drosophila LLC provided the definitive proof.© Jones & Bartlett Learning, LLC the feathers are uniformlyNOT FORcolored SALE and non-OR DISTRIBUTIONOne of Morgan’s students, CalvinNOT Bridges, FOR SALE OR DISTRIBUTION barred. Reciprocal crosses between true-breeding discovered rare exceptions to the expected pat- barred and true-breeding nonbarred breeds give tern of inheritance in crosses with several the results shown, which indicate that the gene X-linked genes. For example, when white-eyed that determines barring must be dominant and Drosophila females were mated with red-eyed must© be Jones located &in theBartlett Z chromosome. Learning, LLC males, most of the© Jonesprogeny & consisted Bartlett of Learning, the LLC NOT FOR SALE OR DISTRIBUTION expected red-eyedNOT females FOR andSALE white-eyed OR DISTRIBUTION Nondisjunction as Proof of the Chromosome males. However, about 1 in every 2000 F1 flies Theory of Heredity was an exception, either a white-eyed female or The parallel between the inheritance of the a red-eyed male. Bridges showed that these rare Drosophila white mutation and the genetic trans- exceptional offspring resulted from occasional © Jones &mission Bartlett of the Learning, X chromosome LLC supported the failure© Jones of the &two Bartlett X chromosomes Learning, in the LLC mother NOT FORchromosome SALE OR theoryDISTRIBUTION of heredity that genes are toNOT separate FOR from SALE each ORother DISTRIBUTION during meiosis—a

4.4 Sex-Chromosome Inheritance 137

26105_CH04_116_153.indd 137 4/27/11 9:32 AM phenomenon called nondisjunction. The con- These and related experiments demon- © Jones & Bartlett Learning,sequence of LLC nondisjunction of the X chromo-© Jones & stratedBartlett conclusively Learning, the LLCvalidity of the chromo- NOT FOR SALE OR DISTRIBUTIONsome is the formation of some eggs withNOT two FOR SALEsome theory OR DISTRIBUTION of heredity. X chromosomes and others with none. Four Chromosome theory of heredity: Genes classes of zygotes are expected from the fertiliza- are physically located within chromosomes. tion of these abnormal eggs (FIGURE 4.19). Ani- mals with no X chromosome are not detected Bridges’s evidence for the chromosome theory because© embryosJones &that Bartlett lack an XLearning, are not viable; LLC was that exceptional© Jonesbehavior & onBartlett the part Learning, of LLC likewise,NOT most FOR progeny SALE with OR three DISTRIBUTION X chromo- chromosomes is preciselyNOT FOR paralleled SALE by ORexcep- DISTRIBUTION somes die early in development. Microscopic tional inheritance of their genes. This proof of the examination of the chromosomes of the excep- chromosome theory ranks among the most tional progeny from the cross white & wild- important and elegant experiments in genetics. type ( showed that the exceptional white-eyed © Jonesfemales & Bartlett had two Learning, X chromosomes LLC plus a Y chro- ©Sex Jones Determination & Bartlett in Drosophila Learning, LLC NOT FORmosome, SALE and OR the DISTRIBUTION exceptional red-eyed males NOTIn the FOR XX–XY SALE mechanism OR DISTRIBUTION of sex determina- had a single X but were lacking a Y. The latter, tion, the Y chromosome is associated with the with a sex-chromosome constitution denoted male. In some organisms, including humans, this XO, were sterile males. association occurs because the presence of the © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC

NOT FOR SALE OR DISTRIBUTIONWhite-eyed female Red-eyedNOT FOR male SALE OR DISTRIBUTION + w ן w w © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Normal sperm

XXX XXY © Jones & Bartlett Learning, LLCRed-eyed female White-eyed© Jones female & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION(usually dies) NOT FOR SALE OR DISTRIBUTION Nondisjunctional eggs

X Y Red-eyed male (sterile) Dies

© Jones & Bartlett Learning,FIGURE 4.19 LLCResults of nondisjunction of the X chromosomes© Jones in &the Bartlett first meiotic divisionLearning, in a female LLC Drosophila. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

138 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 138 4/27/11 9:32 AM Y chromosome triggers events in embryonic elements or XSE (Figure 4.20). If the amount of © Jones development& Bartlett Learning,that result in LLCthe male sexual char- XSE© Jonesis high, the & Bartlettearly burst Learning,occurs and the LLC organ- NOT FORacteristics SALE OR (Chapter DISTRIBUTION 8). Drosophila is unusual ismNOT becomes FOR female; SALE whereas OR DISTRIBUTION if the amount of among organisms with an XX–XY type of sex XSE is low, the early burst does not occur and the determination because the Y chromosome, organism becomes male (Figure 4.20). For almost although associated with maleness, is not male 100 years geneticists believed that sex was deter- determining. This is demonstrated by the finding, mined by the ratio of the number of X chromo- shown in FIGURE 4.20, that© Jones XXY embryos & Bartlett in Dro- Learning,somes LLC (X) relative to the number© Jonesof sets of& Bartlett Learning, LLC sophila develop into NOTmorphologically FOR SALE normal, OR DISTRIBUTIONautosomes (A). The correlation is perfect.NOT InFOR nor- SALE OR DISTRIBUTION fertile females, whereas XO embryos develop mal females (XXAA) the ratio equals 1, in normal into morphologically normal, but sterile, males. males (XAA) it equals 1/2, and in rare individuals (The O is written in the formula XO to emphasize of composition XXAAA the ratio is 2/3 and the that a sex chromosome is missing.) The sterility organism develops as an intersex. Furthermore, of XO© malesJones shows & Bartlett that the Learning, Y chromosome, LLC rare XA haploids© initially Jones develop & Bartlett as female, Learning, LLC thoughNOT not FORnecessary SALE for maleOR DISTRIBUTIONdevelopment, is although they eventuallyNOT FOR die, which SALE again OR sup- DISTRIBUTION essential for male fertility; in fact, the Drosophila ports the idea that an embryo with a ratio of X : Y chromosome contains six genes required for A of 1/2 develops as male, an embryo with an the formation of normal sperm. X : A ratio of 1 develops as a female, and an The genetic determination of sex in Drosoph- embryo with an X : A ratio between 1/2 and 1 © Jones &ila Bartlettdepends on Learning, an X-linked LLC gene known as Sex- develops© Jones as an & intersex.Bartlett Learning, LLC NOT FORlethal SALE (Sxl OR) because DISTRIBUTION some mutant alleles are NOTWhile FOR the SALEcorrelation OR with DISTRIBUTION X : A is perfect, lethal when present in males. The Sxl gene is however, recent data show that the hypothesis is active in normal females and inactive in normal wrong. Sex in Drosophila is based on Sxl reacting males. The product of Sxl is the Sex-lethal protein to the amount of XSE, which in normal flies is SXL, which is an RNA-binding protein that binds determined by the number of X chromosomes. with the RNA transcripts© Jones of several & Bartlett genes and Learning, The autosomes LLC do play a role but© notJones in sex & Bartlett Learning, LLC causes female-specificNOT RNA FOR processing. SALE In OR the DISTRIBUTIONdetermination. Their role is in determiningNOT FOR when SALE OR DISTRIBUTION absence of SXL, these transcripts undergo male- in early development the commitment to sexual specific processing. Hence the targets of SXL are differentiation takes place. In normal XXAA or genes whose protein products are normally made XAA embryos with two sets of autosomes, com- only in females. One of the targets of SXL is the mitment takes place after 15 cycles of division. In Sxl gene© Jones itself, so & aBartlett small burst Learning, of SXL activity LLC XA haploid embryos© Joneswith one & set Bartlett of autosomes, Learning, LLC earlyNOT in female FOR development SALE OR leadsDISTRIBUTION to self-sus- commitment takesNOT place FOR one SALE cell cycle OR later DISTRIBUTION taining production of SXL because of feedback in when the amount of XSE is sufficient to induce the processing of more Sxl transcripts. Sxl. In XXAAA embryos, some cells commit in What makes for the early burst of SXL is the cycle 13 and have too little XSE to induce Sxe, amount of product produced by a small number whereas other cells commit in cycle 14 and have © Jones &of BartlettX-linked Learning,genes known LLC as X-linked signal enough© Jones XSE & to Bartlett induce SxlLearning,. The result LLC is an NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

High (equivalent to two X chromosomes) SXL protein Female-specific Normal © Jones &Sxl Bartlett ON Learning, LLC © Jones & Bartlett Learning, LLC produced transcripts female NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Some cells Amount of SXL protein Female-specific Intermediate Sxl ON protein from produced in transcripts in some Intersex X-linked signal Sxl OFF some cells, cells, male-specific elements© Jones (XSE) & Bartlett Learning, LLC not in others transcripts© Jones in other & Bartlett Learning, LLC Other cells cells NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION SXL protein Male-specific Normal Sxl OFF Low not produced transcripts male (equivalent to one X chromosome) © Jones &FIGURE Bartlett 4.20 Early Learning, steps in the genetic LLC control of sex determination in© Drosophila Jones through & Bartlett the activity Learning,of the Sex-lethal LLCgene Sxl. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.4 Sex-Chromosome Inheritance 139

26105_CH04_116_153.indd 139 4/27/11 9:32 AM embryo that is a mosaic of male and female cells, born earlier and has no influence whatsoever © Jones & Bartlett Learning,and the phenotypic LLC result is an intersex.© Jones & onBartlett the distribution Learning, of sexes LLC of any siblings born NOT FOR SALE OR DISTRIBUTIONSex determination in Drosophila is anNOT excel- FOR SALElater. Each OR successive DISTRIBUTION birth is independent of all lent example of why correlation does not neces- the others. When possible outcomes are inde- sarily mean causation, and of the principle that pendent, the multiplication rule states that the ideas in science, even those that are long probability of any combination of outcomes entrenched and widely believed, sometimes being realized equals the product of the proba- turn out© Jonesto be wrong. & Bartlett Learning, LLC bilities of all the individual© Jones outcomes& Bartlett taken Learning, LLC NOT FOR SALE OR DISTRIBUTION separately. For example,NOT FORthe probability SALE OR that DISTRIBUTION a 4.5 Probability in the Prediction sibship of three children will consist of three of Progeny Distributions girls equals 12 12 12, because the probability of each birth resulting in a girl is 12, Genetic transmission includes a large compo- and the successive births are independent. nent of chance. A particular gamete from an Aa © Jones & Bartlett Learning, LLC ©Probability Jones & calculationsBartlett Learning, in genetics LLC fre- organism might or might not include the A NOT FOR SALE OR DISTRIBUTION quentlyNOT useFOR the SALE addition OR and DISTRIBUTION multiplication allele, depending on chance. A particular gam- rules together. For example, the probability that ete from an Aa Bb organism might or might not all three children in a family will be of the same include both the A and B alleles, depending on sex uses both the addition and the multiplica- the chance orientation of the chromosomes on tion rules. The probability that all three will be the metaphase I plate. Genetic ratios result not © Jones & Bartlett Learning, LLC © Jones & girlsBartlett is (12)(1 Learning,2)(12) LLC 18, and the probabil- only from the chance assortment of genes into NOT FOR SALE OR DISTRIBUTION NOT FOR SALEity that ORall three DISTRIBUTION will be boys is also 18. Because gametes, but also from the chance combination these outcomes are mutually exclusive (a sib- of gametes into zygotes. Although exact predic- ship of size three cannot include three boys and tions are not possible for any particular event, it three girls), the probability of either three girls is possible to determine the probability that a or three boys is the sum of the two probabilities, particular event will be realized, as we saw in © Jones & Bartlett Learning, LLC or 18 18 1©4. Jones The other & Bartlett possible out- Learning, LLC Chapter 3. In this section, we consider some NOT FOR SALE OR DISTRIBUTION comes for sibships ofNOT size FORthree areSALE that ORtwo DISTRIBUTIONof additional probability methods used in inter- the children will be girls and the other a boy, preting genetic data. and that two will be boys and the other a girl. Using the Binomial Distribution in Genetics For each of these outcomes, three different orders of birth are possible—for example, GGB, The addition rule of probability deals with © Jones & Bartlett Learning, LLC GBG,© Jones and BGG—each & Bartlett having Learning, a probability LLC of outcomes of a genetic cross that are mutually NOT FOR SALE OR DISTRIBUTION 12NOT 1 FOR2 1SALE2 1OR8. TheDISTRIBUTION probability of exclusive. Outcomes are “mutually exclusive” two girls and a boy, disregarding birth order, is if they are incompatible in the sense that they the sum of the probabilities for the three possi- cannot occur at the same time. For example, the ble orders, or 38; likewise, the probability of possible sex distributions among three children two boys and a girl is also 38. Therefore, the consist of four mutually exclusive outcomes: © Jones & Bartlett Learning, LLC © Jones & distributionBartlett Learning, of probabilities LLC for the sex ratio in zero, one, two, or three girls. These outcomes NOT FOR SALE OR DISTRIBUTION NOT FOR SALEfamilies OR with DISTRIBUTION three children is have probabilities 18, 38, 38, and 18, respectively. The addition rule states that the overall GGG GGB GBB BBB probability of any combination of mutually GBG BGB exclusive events is equal to the sum of the prob- BGG BBG abilities© ofJones the events & Bartlett taken Learning,separately. ForLLC (1/2)3 3(1/2)2(1/2)© Jones 3(1/2)(1/2) & Bartlett2 (1/2) 3Learning, LLC example, the probability that a sibship of size NOT FOR SALE OR DISTRIBUTION 1/8 3/8 NOT FOR3/8 SALE 1/8 OR DISTRIBUTION1 three contains at least one girl includes the outcomes one, two, and three girls, so the The sex ratio information in this display can be overall probability of at least one girl equals obtained more directly by expanding the bino- 38 38 18 78. mial expression (p q)n, in which p is the prob- © Jones & BartlettThe multiplication Learning, rule LLC of probability deals ability© Jones of the & birth Bartlett of a Learning,girl (12), q LLC is the NOT FORwith SALE outcomes OR DISTRIBUTIONof a genetic cross that are inde- probabilityNOT FOR of the SALE birth of OR a boy DISTRIBUTION (1 2), and n is the pendent. Any two possible outcomes are inde- number of children. In the present example, pendent if the knowledge that one outcome is (p q)3 1p3 3p2q 3pq2 1q3 actually realized provides no information about whether the other is realized also. For example, in which the red numerals are the possible © Jones & Bartlett Learning,in a sequence LLC of births, the sex of any particular© Jones & numberBartlett of Learning, birth orders LLC for each sex distribu- NOT FOR SALE OR DISTRIBUTIONchild is not affected by the sex of anyNOT sibling FOR SALEtion. Similarly, OR DISTRIBUTION the binomial distribution of

140 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 140 4/27/11 9:32 AM probabilities for the sex ratios in families of five n Coefficients © Jones children& Bartlett is Learning, LLC ©0 Jones & Bartlett Learning,1 LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ( p q)5 1p5 5p4q 10p3q2 1 1 1 10p2q3 5pq4 1q5 2 1 21 3 1 33 1 Each term tells us the probability of a particular 4 1 4 614 combination. For example,© Jones the third & Bartlett term is the Learning, LLC © Jones & Bartlett Learning, LLC probability of three girls (p3) and two boys (q2) 5 115 10 10 5 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION in a family that has five children: 6 1 6 15 20 15 6 1 10(12)3(12)2 1032 516 7 137 21 35 521 7 1 There are n 1 terms in a binomial expan- 8 178 28 56 056 28 8 1 sion to© theJones power & n .Bartlett The exponents Learning, of p decrease LLC 9 1 9 36© Jones84 126 &126 Bartlett84 36 Learning, 9 1 LLC by one from n in the first term to 0 in the last 10 1 10 45 120 210 252 210 120 45 10 1 term,NOT and theFOR exponents SALE ORof q DISTRIBUTIONincrease by one NOT FOR SALE OR DISTRIBUTION from 0 in the first term to n in the last term. The FIGURE 4.21 Pascal’s triangle. The numbers in the nth row are the n coefficients generated by successive values of n coefficients of the terms in the expansion of the polynomial (p q) . can be arranged in a regular triangle known as © Jones &Pascal’s Bartlett triangle Learning,, shown LLC for n 0 to 10 in © Jones & Bartlett Learning, LLC FIGURE 4.21. The horizontal rows of the triangle Table 4.2 Factorials NOT FORare SALE symmetrical; OR DISTRIBUTION each row begins and ends with NOT FOR SALE OR DISTRIBUTION n n! n n! a 1, and each other entry can be obtained as the sum of the two numbers on either side of it in 0 1 8 40,320 the row above. 1 1 9 362,880 2 2 10 3,628,800 To generalize just© a bit,Jones if the & probability Bartlett ofLearning, LLC © Jones & Bartlett Learning, LLC event A is p, that of event B is q, and the two 3 6 11 39,916,800 events are independentNOT and FORmutually SALE exclusive, OR DISTRIBUTION4 24 12 NOT479,001,600 FOR SALE OR DISTRIBUTION then the probability that A will be realized four 5 120 13 6,227,020,800 times and B two times (in a specified order) is, by 6 720 14 87,178,291,200 the multiplication rule, p4q2. Usually we are 7 5040 15 1,307,674,368,000 interested© Jones in a combination & Bartlett of Learning, events regardless LLC © Jones & Bartlett Learning, LLC of their order, such as “four A and two B.” In this NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION case, we multiply the probability that the combi- the product of all positive integers from nation 4A : 2B will be realized in any specified 1 through n (that is, n! 1 2 3 · · · n). order by the number of possible orders. The Values n factorial from n 0 through n 15 number of different combinations of six events, are given in TABLE 4.2. The value 0! 1 is four of type A and two of type B, is given by the © Jones & Bartlett Learning,4 2 LLC defined© Jones arbitrarily & Bartlett to generalize Learning, its use inLLC math- coefficient of p q in the expansion of ematical formulas. The magnitude of n! NOT FOR( pSALE A q ORB)6. ThisDISTRIBUTION coefficient can be found in the NOT FOR SALE OR DISTRIBUTION increases very rapidly; 15! is more than a row for n 6 in Pascal’s triangle, as the fifth trillion. entry from the left. (It is the fifth because the 0 6 1 5 Equation (1) applies even when either s or successive entries are the coefficients of p q , p q , t equals 0 because 0! 1. (Remember also that p2q4, p3q3, p4q2, p5q1, and p6q0.) Hence, the overall © Jones & Bartlett Learning,any number LLC raised to the zero power© Jonesequals 1.) & Bartlett Learning, LLC probability of four realizations of A and two real- Any individual term in the expansion of the NOT FOR SALE4 2 OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION izations of B in six trials is given by 15p q . binomial (p q)n is given by Equation (1) for The general rule for repeated trials of events the appropriate values of s and t. In Pascal’s tri- with constant probabilities is as follows: angle, successive entries in the nth row are the If the probability of event A is p and the prob- values of n! (s! t!) for s 0, 1, 2, . . . , n. ability© Jones of the &alternative Bartlett event Learning, B is q, the LLC Let us consider© Jones a specific & Bartlettapplication Learning, of LLC probabilityNOT FOR that, SALE in n trials, OR event DISTRIBUTION A is realized Equation (1), in whichNOT weFOR calculate SALE the OR proba- DISTRIBUTION s times and event B is realized t times is bility that a mating between two heterozygous n! parents will yield exactly the expected 3 : 1 ratio psqt (1) of the dominant and recessive traits among sib- s!t! ships of a particular size. The probability p of a © Jones &in whichBartlett s Learning, t n and p LLC q 1. The sym- child© Jones showing & the Bartlett dominant Learning, trait is 34, LLC and the NOT FORbol SALE n! is readOR asDISTRIBUTION “n factorial,” and it stands for probabilityNOT FOR q ofSALE a child OR showing DISTRIBUTION the recessive

4.5 Probability in the Prediction of Progeny Distributions 141

26105_CH04_116_153.indd 141 4/27/11 9:32 AM trait is 14. Suppose we wanted to know how distinguished among themselves. However, © Jones & Bartlett Learning,often families LLC with eight children ©contain Jones & applyingBartlett againLearning, the argument LLC we just used, NOT FOR SALE OR DISTRIBUTIONexactly six children with the dominantNOT pheno- FOR SALEeach of OR the DISTRIBUTIONn! particular arrangements must type and two with the recessive phenotype. This include s! different arrangements of the s ele- is the “expected” Mendelian ratio. In this case, ments and t! different arrangements of the t n 8, s 6, t 2, and the probability of this elements, or s! t! altogether. Dividing n! by combination of events is s! t! therefore yields the binomial coefficient © Jones & Bartlett Learning, LLC for the number of© ways Jones in which& Bartlett the s ele-Learning, LLC 8! 8! NOT FOR SALE OR DISTRIBUTION ments and the t elementsNOT FOR can SALE be arranged OR DISTRIBUTION p6q2 (34)6(14)2 0.31 6! 2! 6! 2! when the elements of each type are not distinguished among themselves. That is, in only 31 percent of the families with eight children would the offspring exhibit the 4.6 Testing Goodness of Fit © Jonesexpected & Bartlett 3 : 1 Learning,phenotypic ratio;LLC the other sib- © Jonesto a Genetic& Bartlett Hypothesis Learning, LLC NOT FORships SALE would OR deviate DISTRIBUTION in one direction or the other NOT FOR SALE OR DISTRIBUTION because of chance variation. The importance of Geneticists often need to decide whether an this example is in demonstrating that although observed ratio is in satisfactory agreement a 3 : 1 ratio is the “expected” outcome (and is with a theoretical prediction. Mere inspection also the single most likely outcome), the major- of the data is unsatisfactory because different © Jones & Bartlett Learning,ity of the families LLC (69 percent) actually© have Jones a & investigatorsBartlett Learning, may disagree. LLC Suppose, for NOT FOR SALE OR DISTRIBUTIONdistribution of offspring different from 3NOT : 1. FOR SALEexample, OR that DISTRIBUTION we crossed a plant having purple flowers with a plant having white flowers and, among the progeny, observed 14 plants Meaning of the Binomial Coefficient with purple flowers and 6 with white flowers. The factorial part of the binomial expansion Is this result close enough to be accepted as a in Equation© Jones (1), which & Bartlett equals nLearning,!(s! t!), is called LLC 1 : 1 ratio? What if ©we Jones observed & 15Bartlett plants with Learning, LLC the binomialNOT FORcoefficient SALE. As weOR have DISTRIBUTION noted, this purple flowers andNOT 5 with FOR white SALE flowers? OR DISTRIBUTIONIs ratio enumerates all possible ways in which this result consistent with a 1 : 1 ratio? There s elements of one kind and t elements of another is bound to be statistical variation in the kind can be arranged in order, provided that the observed results from one experiment to the s elements and the t elements are not distin- next. Who is to say what results are consistent © Jonesguished & Bartlett among Learning, themselves. LLC A specific example with© Jonesa particular & Bartlett genetic hypothesis?Learning, LLCIn this NOT FORmight SALE include OR sDISTRIBUTION yellow peas and t green peas. section,NOT we FOR describe SALE a test OR of DISTRIBUTIONwhether observed Although the yellow peas and the green peas results deviate too far from a theoretical can be distinguished from each other because expectation. The test is called a test for good- they have different colors, the yellow peas are ness of fit, where the word fit means how not distinguishable from one another (because closely the observed results “fit,” or agree © Jones & Bartlett Learning,they are all LLC yellow), nor are the green© Jones peas & with,Bartlett the expectedLearning, results. LLC NOT FOR SALE OR DISTRIBUTION(because they are all green). NOT FOR SALE OR DISTRIBUTION The reasoning behind the factorial formula The Chi-Square Method begins with the observation that the total num- A conventional measure of goodness of fit ber of elements is s t n. Given n elements, is a value called chi-square (its symbol is ␹2), each distinct from the next, the number of dif- which is calculated from the number of progeny ferent ©ways Jones in which & Bartlett they can Learning,be arranged is:LLC observed in each of© various Jones classes, & Bartlett compared Learning, LLC with the number expected in each of the classes n NOT (n 1)FOR (n SALE 2) OR . . . DISTRIBUTION 3 2 1 NOT FOR SALE OR DISTRIBUTION on the basis of some genetic hypothesis. For Why? Because the first element can be chosen example, in a cross between plants with purple in n ways, and once it is chosen, the next can flowers and those with white flowers, we may be chosen in n 1 ways (because only be interested in testing the hypothesis that the © Jonesn & Bartlett 1 are left Learning, to choose from), LLC and once the parent© Jones with purple & Bartlett flowers Learning, is heterozygous LLC for NOT FORfirst SALE two are OR chosen, DISTRIBUTION the third can be chosen oneNOT pair ofFOR alleles SALE determining OR DISTRIBUTION flower color and in n 2 ways, and so on. Finally, once that the parent with white flowers is homozy- n 1 elements have been chosen, there gous recessive. Suppose further that we exam- is only one way to choose the last element. ine 20 progeny plants from the mating and find The s t elements can be arranged in n! that 14 are purple and 6 are white. The proce- © Jones & Bartlett Learning,ways, provided LLC that the elements ©are Jones all & dureBartlett for testing Learning, this genetic LLC hypothesis (or any NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

142 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 142 4/27/11 9:32 AM other genetic hypothesis) by means of the chi- In symbols, the calculation of ␹ 2 can be repre- © Jones square& Bartlett method Learning, is as follows: LLC sented© Jones by the & expression Bartlett Learning, LLC 1. State the genetic hypothesis in detail, NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (Observed Expected)2 specifying the genotypes and pheno- ␹2 types of the parents and the possible Expected progeny. In the example using flower color, the genetic hypothesis implies in which means the summation over all the ␹ 2 that the genotypes© Jones in the & cross Bartlett purple Learning, classes LLC of progeny. Note that ©is calculatedJones & Bartlett Learning, LLC white couldNOT be symbolized FOR SALE as PpOR DISTRIBUTIONusing the observed and expected NOTnumbers FOR, not SALE OR DISTRIBUTION pp. The possible progeny genotypes are the proportions, ratios, or percentages. Using Pp and pp. something other than the actual numbers is the 2. Use the rules of probability to make most common beginner’s mistake in applying ␹ 2 ␹ 2 explicit predictions of the types and the method. The value is reasonable as a ©proportions Jones & Bartlettof progeny Learning, that should LLC be measure of goodness© Jones of fit, because& Bartlett the closer Learning, LLC NOTobserved FOR if SALEthe genetic OR hypothesis DISTRIBUTION is true. the observed numbersNOT are FOR to the SALE expected OR num- DISTRIBUTION ␹ 2 Convert the proportions to numbers of bers, the smaller the value of . A value of ␹ 2 progeny (percentages are not allowed in 0 means that the observed numbers fit a ␹ 2 test). If the hypothesis about the the expected numbers perfectly. ␹2 flower-color cross is true, then we should As another example of the calculation of , © Jones & Bartlettexpect Learning, the progeny LLC genotypes Pp and suppose© Jones that & the Bartlett progeny Learning, of an F1 LLCF1 cross NOT FOR SALEpp toOR occur DISTRIBUTION in a ratio of 1 : 1. Because the includesNOT FOR two contrasting SALE OR phenotypes DISTRIBUTION observed in hypothesis is that Pp flowers are purple the numbers 99 and 45. In this case the genetic and pp flowers are white, we expect hypothesis might be that the trait is determined the phenotypes of the progeny to be by a pair of alleles of a single gene, in which case purple or white in the ratio 1 : 1. Among the expected ratio of dominant : recessive pheno- 20 progeny, the© Jonesexpected & numbers Bartlett are Learning, types amongLLC the F2 progeny is 3 : 1.© Considering Jones & Bartlett Learning, LLC 10 purple and NOT10 white. FOR SALE OR DISTRIBUTIONthe data, the question is whether NOTthe observed FOR SALE OR DISTRIBUTION 3. For each class of progeny in turn, sub- ratio of 99 : 45 is in satisfactory agreement with ␹2 tract the expected number from the the expected 3 : 1. Calculation of the value of observed number. Square this dif- is illustrated in TABLE 4.3. The total number of prog- ference and divide the result by the eny is 99 45 144. The expected numbers in © expectedJones number.& Bartlett In Learning,our example, LLC the the two classes, ©on Jones the basis & Bartlettof the genetic Learning, LLC NOTcalculation FOR SALEfor the OR purple DISTRIBUTION progeny is hypothesis that theNOT true FORratio is SALE 3 : 1, are OR calcu- DISTRIBUTION (14 10)210 1.6, and that for the lated as (3 4) 144 108 and (1 4) white progeny is (6 10)210 1.6. 144 36. Because there are two classes of data, ␹2 4. Sum the result of the numbers cal- there are two terms in the calculation: culated in step 3 for all classes of 2 2 ␹2 (99 108) (45 36) © Jones & Bartlettprogeny. Learning, The summation LLC is the value © Jones & Bartlett Learning, LLC NOT FOR SALEof OR␹ 2 for DISTRIBUTION these data. The sum for the NOT FOR SALE108 OR DISTRIBUTION36 purple and white classes of progeny is 0.75 2.25 1.6 1.6 3.2, and this is the value 3.00 of ␹ 2 for the experiment, calculated Once the ␹2 value has been calculated, the on the assumption that our genetic next step is to interpret whether this value rep- hypothesis is correct.© Jones & Bartlett Learning,resents LLC a good fit or a bad fit to the© Jones expected & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Table 4.3 Calculation of ␹ 2 for a monohybrid ratio © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC (Deviation)2 PhenotypeNOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION (class) Observed number Expected number Deviation from expected expected number Wildtype 99 108 9 0.75 Mutant 45 36 9 2.25 Total 144 144 ␹ 2 3.00 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

4.6 Testing Goodness of Fit to a Genetic Hypothesis 143

26105_CH04_116_153.indd 143 4/27/11 9:32 AM 1.00 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 0.90 30 NOT FOR SALE0.80 OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 25 18 0.70 20 0.60 16 14 0.50 12 10 7 0.40 © Jones & Bartlett Learning, LLC 8 © Jones & Bartlett Learning, LLC 6 5 0.30 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 43 Degrees of freedom

P 0.20 2 1 0.15

0.10© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 0.08NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

0.05

0.03 P values in this region © Jones & Bartlett0.02 Learning, LLC © Jones & Bartlett Learning,are statistically LLC P values NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION“significant.” indicate 0.01 hypothesis P values in should be 0.005 this region are rejected. statistically “highly Probability of fit as bad or worse by chance (0.002 ) © Jones & Bartlett Learning, LLC significant.”© Jones & Bartlett Learning, LLC 0.001 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

0.0005 0.0003

0.0001© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 50 40 30 25 20 18 16 14 12 10 9 8 7 6 5 4 3 2 1 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION0.6 0.4 0.2 0.1 Calculated 2 value FIGURE 4.22 Graphs for interpreting goodness of fit to genetic predictions using the chi-square test. For any calculated value of 2 along the x-axis, the y-axis gives the probability P that chance alone would produce a fit as bad as or worse than that actually observed, when the genetic predictions are correct. Tests with P in the pink region (less than 5 percent) or in the green region (less than 1 percent) are regarded as statistically significant and normally require rejection of the genetic hypothesis that led to the prediction. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

numbers. This assessment is done with the aid In practice, the critical values of P are con- of the graphs in FIGURE 4.22. The x-axis gives the ventionally chosen as 0.05 (the 5 percent level) ␹2 values© Jones that reflect & Bartlett goodness Learning, of fit, and theLLC and 0.01 (the 1 percent© Jones level). & BartlettFor P values Learning, LLC y-axis gives the probability P that a worse fit (or ranging from 0.01 to 0.05, the probability that one equallyNOT bad)FOR would SALE be obtainedOR DISTRIBUTION by chance, chance alone wouldNOT lead toFOR a fit asSALE bad or OR worse DISTRIBUTION assuming that the genetic hypothesis is true. If is between 1 in 20 experiments and between the genetic hypothesis is true, then the observed 1 in 100, respectively. This is the middle region numbers should be reasonably close to the in Figure 4.22; if the P value falls in this range, © Jonesexpected & Bartlett numbers. Learning, Suppose LLC that the observed the© correctness Jones & of Bartlett the genetic Learning, hypothesis LLC is con- ␹2 is so large that the probability of a fit as bad sidered very doubtful. The result is said to be NOT FORor SALEworse is ORvery DISTRIBUTIONsmall. Then the observed results statisticallyNOT FOR significant SALE OR at theDISTRIBUTION 5 percent level. do not fit the theoretical expectations. This For P values smaller than 0.01, the probability means that the genetic hypothesis used to cal- that chance alone would lead to a fit as bad or culate the expected numbers of progeny must worse is less than 1 in 100 experiments. This is © Jones & Bartlett Learning,be rejected, LLC because the observed numbers© Jones of & theBartlett lower regionLearning, in Figure LLC 4.22; in this case, the progeny deviate too much from the expected result is said to be highly significant at the NOT FOR SALE OR DISTRIBUTIONnumbers. NOT FOR SALE1 percent OR level, DISTRIBUTION and the genetic hypothesis is 144 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 144 4/27/11 9:32 AM connection © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORSeeds SALE OR of DISTRIBUTIONDoubt NOT FOR SALE OR DISTRIBUTION

R. A. Fisher, one of the founders of find that the proportion of plants plants, were grown on this occa- modern statistics, was also interested misclassified by this test is not inap- sion, the greater part of the discrep- ©in Jones genetics. & He Bartlett preciable. Learning, Between LLC 5 and 6 percent ancy would© Jones be removed. & Bartlett . . . Such Learning, LLC Ronald Aylmer Fisher 1936 gave Mendel’s of the heterozygous plants will be an explanation, however, could not University College, NOTdata FORa thor- SALEclassified OR DISTRIBUTION as homozygous. . . . Now explain theNOT discrepancy FOR SALE observed OR DISTRIBUTIONin London, England ough going among 600 plants tested by Mendel the first group of experiments, in Has Mendel’s Work Been over and made 201 were classified as which the procedure is Rediscovered? an “abomina- homozygous and 399 The reconstruction [of specified, without the © Jones & Bartlettble discovery.” Learning, as heterozygous.LLC . . . Mendel’s© Jones experiments] & Bartlett occurrence Learning, of a coinci-LLC Fisher’s unpleasant discovery was that The deviation [from dence of considerable NOT FOR SALE OR DISTRIBUTION givesNOT no FOR doubt SALE OR DISTRIBUTION some of Mendel’s experiments yielded a the true expected val- whatever that his report improbability. . . . The better fit to the wrong expected values ues of 222 and 378] is is to be taken entirely reconstruction [of than they did to the right expected values. one to be taken seri- Mendel’s experiments] literally, and that his At issue are two series of experiments con- ously. . . . A deviation as gives no doubt what- experiments were © Jones &sisting Bartlett of progeny Learning, tests in which LLC F2 plants fortunate as Mendel’s© Jones is & Bartlett Learning, everLLC that his report is with the dominant phenotype were self- to be expected once in carried out in just the to be taken entirely lit- NOT FORfertilized SALE and OR their DISTRIBUTION progeny examined for twenty-nine trials.NOT . FOR. . waySALE and ORmuch DISTRIBUTION in the erally, and that his segregation to ascertain whether each [In the second series of order that they are experiments were car- parent was heterozygous or homozygous. experiments], a total recounted. ried out in just the way In the first series of experiments, Mendel deviation of the magni- and much in the order explicitly states that he cultivated© Jones 10 seeds& Bartlett tude observed, Learning, and inLLC the right direc- that they© Jones are recounted. & Bartlett TheLearning, LLC from each plant. What Mendel did not tion, is only to be expected once in detailed reconstruction of his pro- realize, apparently, is thatNOT inferring FOR theSALE 444 OR trials; DISTRIBUTION there is therefore a serious grammeNOT on this FOR assumption SALE leads OR DISTRIBUTIONto genotype of the parent on the basis of the discrepancy. . . . If we could suppose no discrepancy whatsoever. A phenotypes of 10 progeny introduces a that larger progenies, say fifteen serious and almost inexplicable slight bias. The reason is shown in the accompanying© Jones illustration. & Bartlett Because Learning, a frac- LLC © Jones & Bartlett Learning, LLC ן 10 tion (3/4) of all progenies from a hetero- The experiment: F1 Aa F1 Aa zygousNOT parent FOR will not SALE exhibit ORsegregation, DISTRIBUTION NOT FOR SALE OR DISTRIBUTION purely as a result of chance, this propor- (Self each one) ן Choose A– progeny tion of Aa parents gets misclassified as AA. F2 generation The expected proportion of “apparent” AA plants is (1/3) (2/3)(3/4)10 and that © Jones &of AaBartlett plants is Learning, (2/3)[1 (3/4) LLC10], for a © Jones & BartlettExamine 10 Learning, progeny from LLC each; NOT FOR SALE OR DISTRIBUTION NOT FOR SALEif no recessive OR DISTRIBUTION progeny, conclude ratio of 0.37 : 0.63. In the first series of that parent was AA experiments, among 600 plants tested, Mendel reports a ratio of 0.335 : 0.665, What is the expected ratio of AA : Aa ? which is in better agreement with the Possible F genotypes AA Aa incorrect expectation of 0.33 : 0.67 than 2 © Jones & Bartlett Learning, LLC 1 © Jones2 & Bartlett Learning, LLC with 0.37 : 0.63. In the second series of Original ratio in F2 /3 /3 experiments, among 473 NOTprogeny, FOR Mendel SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION reports a ratio of 0.32 : 0.68, which is again (3/4)10 1–(3/4)10 Progeny from No homozygous By chance, yield Yield at least in better agreement with 0.33 : 0.67 than self-fertilization recessives no homozygous one homozygous with 0.37 : 0.63. Modern scholars have recessives recessive concluded© Jones that Fisher & Bartlettmost likely misinter-Learning, LLC © Jones & Bartlett Learning, LLC preted Mendel’s description of the second These get classified These get These get classified NOT FOR SALE OR DISTRIBUTION correctlyNOT as AA FORmisclassified SALE OR DISTRIBUTIONcorrectly as Aa series of experiments, and that the results of as AA Mendel’s first series of experiments actually fit Fisher’s expectation very well. Expected ratio 1/3 + (2/3)(3/4)10 (2/3)[1–(3/4)10] In connection with these tests after selfing = 0.3709 = 0.6291 of homozygosity by examin- © Jones & Bartlett Learning, LLC Mendel’s incorrect© Jones & Bartlett Learning, LLC ing ten offspring formed by self- 0.3333 0.6667 expectations NOT FORfertilization, SALE OR itDISTRIBUTION is disconcerting to NOT FOR SALE OR DISTRIBUTION (continued on page 146)

26105_CH04_116_153.indd 145 4/27/11 9:33 AM connection © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORSeeds SALE OR of DISTRIBUTIONDoubt, cont. NOT FOR SALE OR DISTRIBUTION

discrepancy has, however, from what should have been among others that Mendel was appeared, in that in two series of expected had his theory been cor- deceived by some assistant who results the numbers ©observed Jones agree & Bartlett rected Learning, to allow for LLCthe small size of knew too© wellJones what & was Bartlett expected. Learning, LLC excellently with the two to one his test progenies. . . . Although no NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION ratio, which Mendel himself explanation can be expected to be Source: R. A. Fisher, Ann. Sci. 1 (1936): expected, but differ significantly satisfactory, it remains a possibility 115–137.

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORrejected SALE outright. OR DISTRIBUTION If the terminology of statisti- produceNOT aFOR ␹2 value SALE as greatOR DISTRIBUTIONas or greater than cal significance seems backward, it is because 3.00 in about 8 percent of experiments of the the term significant refers to the magnitude of type in Table 4.3; and, because the P value is the deviation between the observed and the within the upper region, the goodness of fit to expected numbers; in a result that is statistically the hypothesis of a 3 : 1 ratio of wildtype : mutant © Jones & Bartlett Learning,significant, LLCthere is a large (“significant”)© differ-Jones & isBartlett judged to Learning, be satisfactory. LLC NOT FOR SALE OR DISTRIBUTIONence between what is observed and NOTwhat FORis SALEAs ORa second DISTRIBUTION illustration of the ␹ 2 test, we expected. will determine the goodness of fit of Mendel’s To use Figure 4.22 to determine the P value round-versus-wrinkled data to the expected 3 : 1 corresponding to a calculated ␹2, we need the ratio. Among the 7324 seeds that he observed, number© ofJones degrees & ofBartlett freedom Learning, of the particu- LLC 5474 were round and© Jones1850 were & Bartlettwrinkled. Learning,The LLC lar ␹2 test. For the type of ␹2 test illustrated in expected numbers are (34) 7324 5493 Table 4.3,NOT the FOR number SALE of degreesOR DISTRIBUTION of freedom round and (14) 7324NOT FOR 1831 SALE wrinkled. OR The DISTRIBUTION equals the number of classes of data minus 1. ␹ 2 value is calculated as: Table 4.3 contains two classes of data (wildtype (5474 5493)2 (1850 1831)2 and mutant), so the number of degrees of free- ␹2 © Jonesdom & Bartlett is 2 1 Learning, 1. The reason LLC for subtracting © Jones &5493 Bartlett Learning,1831 LLC 1 is that, in calculating the expected numbers 0.26 NOT FORof progeny,SALE OR we DISTRIBUTIONmake sure that the total num- NOT FOR SALE OR DISTRIBUTION ber of progeny is the same as that actually The fact that the ␹ 2 is less than 1 already implies observed. For this reason, one of the classes of that the fit is very good. To find out how good, data is not really “free” to contain any number note that the number of degrees of freedom we might specify; because the expected num- equals 2 1 1 because there are two © Jones & Bartlett Learning,ber in one LLCclass must be adjusted to make© Jones the & classesBartlett of data Learning, (round and LLC wrinkled). From Fig- NOT FOR SALE OR DISTRIBUTIONtotal come out correctly, one “degree NOTof free- FOR SALEure 4.22, OR the DISTRIBUTION P value for ␹ 2 0.26 with dom” is lost. Analogous ␹2 tests with three 1 degree of freedom is approximately 0.65. This classes of data have 2 degrees of freedom, and means that in about 65 percent of all experi- those with four classes of data have 3 degrees ments of this type, a fit as bad or worse would of freedom. be expected simply because of chance. Only Once© Jones we have & determined Bartlett Learning, the appropriate LLC about 35 percent of© all Jones experiments & Bartlett would yield Learning, LLC numberNOT of degrees FOR ofSALE freedom, OR we DISTRIBUTION can interpret a better fit. NOT FOR SALE OR DISTRIBUTION the ␹2 value in Table 4.3. Refer to Figure 4.22, and observe that each curve is labeled with its Are Mendel’s Data Too Good to Be True? degrees of freedom. To determine the P Many of Mendel’s experimental results are value for the data in Table 4.3, in which very close to the expected values. For the ratios © Jonesthe & Bartlett␹2 value isLearning, 3.00, first findLLC the location of listed© Jones in Table &3.1 Bartlett in Chapter Learning, 3, the ␹2 values LLC are NOT FOR␹2 SALE 3.00 ORalong DISTRIBUTION the x-axis in Figure 4.22. Trace 0.26NOT (round FOR versus SALE wrinkled OR DISTRIBUTION seeds), 0.01 (yel- vertically on this line until you intersect the low versus green seeds), 0.39 (purple versus curve with 1 degree of freedom. Then trace white flowers), 0.06 (inflated versus constricted horizontally to the left until you intersect the pods), 0.45 (green versus yellow pods), 0.35 y-axis, and read the P value; in this case, (axial versus terminal flowers), and 0.61 (long © Jones & Bartlett Learning,P 0.08. ThisLLC means that chance alone© would Jones & versusBartlett short Learning, stems). (As LLC an exercise in ␹2, you NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

146 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 146 4/27/11 9:33 AM should confirm these calculations for yourself.) © Jones All& Bartlett of the ␹ 2Learning, tests have LLCP values of 0.45 or ©20 Jones & Bartlett Learning, LLC NOT FORgreater SALE (Figure OR DISTRIBUTION 4.22), which means that the NOT FOR SALE= Expected OR number DISTRIBUTION 18 reported results are in excellent agreement with = Observed number the theoretical expectations. 16 The statistician Ronald Fisher pointed out in 1936 that Mendel’s results are suspiciously 14 close to the theoretical© expectations.Jones & Bartlett In a large Learning, LLC © Jones & Bartlett Learning, LLC number of experiments,NOT some FOR experiments SALE OR can DISTRIBUTION 12 NOT FOR SALE OR DISTRIBUTION be expected to yield fits that appear doubtful simply because of chance variation from one 10 experiment to the next. In Mendel’s data, the 8 doubtful values that are to be expected appear

© Jones & Bartlett Learning, LLC Number of experiments © Jones & Bartlett Learning, LLC to be missing. FIGURE 4.23 shows the observed 6 deviationsNOT inFOR Mendel’s SALE experiments OR DISTRIBUTION compared NOT FOR SALE OR DISTRIBUTION with the deviations expected by chance. (The 4 measure of deviation is the square root of the ␹2 value, assigned either a plus or a minus sign 2 according to whether the dominant or the © Jones & Bartlett Learning, LLC © 0Jones & Bartlett Learning, LLC recessive phenotypic class was in excess of the 0 –2.5 –2.0 –1.5 –1.0 –0.5 0 0.5 1.0 1.5 2.0 2.5 NOT FORexpected SALE number.)OR DISTRIBUTION For each magnitude of devi- NOT FOR SALE ORDeviation DISTRIBUTION from expectation ation, the height of the bar on the right gives FIGURE 4.23 Distribution of deviations observed in 69 of Mendel’s experiments (yellow the number of experiments that Mendel bars) compared with expected values (orange bars). There is no suggestion that the data observed with such a magnitude of deviation, in the middle have been adjusted to improve the fit, but there are fewer experiments with and that of the bar on the left gives the number large deviations than might be expected. Several experiments with large deviations may have been discarded or repeated. of experiments expected© Jones to deviate & Bartlett by this Learning, LLC © Jones & Bartlett Learning, LLC amount as a result ofNOT chance FOR alone. SALE There OR are DISTRIBUTION NOT FOR SALE OR DISTRIBUTION clearly too few experiments with deviations smaller than 1 or larger than 1. This type of of Mendel’s data in 1966, the evolutionary discrepancy could be explained if Mendel dis- geneticist Sewall Wright concluded, carded or repeated a few experiments with © Jones & Bartlett Learning, LLC Mendel was the© first Jones to count & segregantsBartlett atLearning, all. LLC large deviations that made him suspect that the It is rather too much to expect that he would resultsNOT were FOR not to SALE be trusted. OR DISTRIBUTION be aware of theNOT precautions FOR now SALE known OR to be DISTRIBUTION Did Mendel cheat? Did he deliberately fal- necessary for completely objective data. . . . sify his data to make them appear better? Men- Checking of counts that one does not like, del’s paper reports extremely deviant ratios but not of others, can lead to systematic bias from individual plants, as well as experiments toward agreement. I doubt whether there are © Jones &repeated Bartlett when Learning, the first results LLC were doubtful. © Jonesmany geneticists & Bartlett even now Learning, whose data, LLC if NOT FORThese SALE are OR not DISTRIBUTIONthe kinds of things a dishonest NOTextensive, FOR wouldSALE stand OR up DISTRIBUTION wholly satisfacto- ␹2 person would admit. Only a small bias is neces- rily under the text. . . . Taking everything into account, I am confident that there was no sary to explain the excessive goodness of fit in deliberate effort at falsification. Figure 4.23. In a count of seeds or individual plants, only about 2 phenotypes per 1000 Mendel’s data are some of the most exten- would need to be assigned© Jones to the & wrongBartlett cate- Learning,sive and LLC complete “raw data” ever ©published Jones in& Bartlett Learning, LLC gory to account for theNOT bias inFOR the 91SALE percent OR of DISTRIBUTIONgenetics. Additional examinationsNOT of the FOR data SALE OR DISTRIBUTION the data generated by the testing of monohy- will surely be carried out as new statistical brid ratios. The excessive fit could also be approaches are developed. However, the princi- explained if three or four entire experiments pal point to be emphasized is that up to the pres- were discarded or repeated because deviant ent time, no reputable statistician has alleged results© wereJones attributed & Bartlett to pollen Learning, contamination LLC that Mendel knowingly© Jones and deliberately & Bartlett adjusted Learning, LLC or otherNOT accident. FOR SALE After careful OR DISTRIBUTION reexamination his data in favor ofNOT the theoretical FOR SALE expectation. OR DISTRIBUTION

4.6 Testing Goodness of Fit to a Genetic Hypothesis 147

26105_CH04_116_153.indd 147 4/27/11 9:33 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALEChromosomes OR DISTRIBUTION in eukaryotic cells In many animals,NOT sex FOR is deter- SALE OR DISTRIBUTIONgave experimental proof of the are usually present in pairs. mined by a special pair of chro- chromosomal theory of The chromosomes of each pair mosomes, the X and Y. heredity. separate in meiosis, one going to The “criss-cross” pattern of The progeny of genetic crosses each gamete. © Jones & Bartlettinheritance Learning, of X-linked LLC genes is follow© the Jones binomial & Bartlettprobability Learning, LLC In meiosis, the chromosomesNOT FOR of SALEdetermined OR DISTRIBUTION by the fact that a formula.NOT FOR SALE OR DISTRIBUTION different pairs undergo indepen- male receives his X chromosome The chi-square statistical test is dent assortment because nonho- only from his mother and trans- used to determine how well the mologous chromosomes move mits it only to his daughters. observed genetic data agree with independently. Irregularities in the inheritance the expectations derived from a © Jones & Bartlett Learning,of LLC an X-linked gene in Drosophila© Jones hypothesis. & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

What is the genetic significance of the fact Explain the following statement: “Indepen- In what ways is the inheritance of a Y-linked © Jones & thatBartlett gametes containLearning, half the chromosome LLC dent alignment of© nonhomologous Jones & Bartlett Learning,gene different fromLLC that of an X-linked gene? complement of somatic cells? chromosomes at metaphase I of meiosis is How did nondisjunction “prove” the NOT FOR SALEThe term ORmitosis DISTRIBUTION derives from the Greek the physical basisNOT of independent FOR SALEassort- OR DISTRIBUTIONchromosome theory of heredity? ment of genes in different chromosomes.” mitos, which means “thread.” The term Why is a statistical test necessary to deter- meiosis derives from the Greek meioun, What are some of the important differences mine whether an observed set of data yields which means “to make smaller.” What between the first meiotic division and the an acceptable fit to the result expected feature, or features, of these types of second meiotic division? from a particular genetic hypothesis? nuclear division might have led to the Draw a diagram of a bivalent and label the choice of these terms? © Jones & Bartlett Learning, LLC What statistical© Jones test is often & Bartlett used for this Learning, LLC following parts: centromere, sister chroma- purpose? Explain the meaning of theNOT terms FORreduc- SALEtids, OR nonsister DISTRIBUTION chromatids, homologous NOT FOR SALE OR DISTRIBUTION tional division and equational division. What chromosomes, chiasma. What are the conventional P values for is reduced or kept equal? To which nuclear significant and highly significant, and what What are the principal characteristics of do these numbers mean? divisions do the terms refer? human pedigrees in which a rare X-linked recessive allele is segregating? © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

1 the overall probability of an affected son is ( ⁄2) 0 1 1 1 A recessive mutation in an X-linked gene results ( ⁄2) ( ⁄2) ⁄4. © Jones &in hemophilia,Bartlett Learning, marked by a LLCprolonged increase in the time© Jones & Bartlett Learning, LLC NOT FORneeded SALE for OR blood DISTRIBUTION to clot. Suppose that two phenotypicallyNOT FOR SALE In a sibship OR withDISTRIBUTION seven children, what is the prob- normal parents produce three normal daughters and a son ability that it includes four boys and three girls or three affected with hemophilia. boys and four girls? Assume that each child has an equal (a) What is the probability that all of the daughters are likelihood of being a boy or a girl. heterozygous carriers? (b) If one of the daughters© Jones mates with& Bartlett a normal Learning,male and LLCAnswer The probability that ©the Jones sibship & consists Bartlett of four Learning, LLC produces a son, what is the probability that the son boys and three girls, in any order of birth, equals [7!/ NOT FOR SALE OR DISTRIBUTION 1 4 1 3 NOT FOR SALE OR DISTRIBUTION will be affected? (4!3!)]( ⁄2) ( ⁄2) , where the factor in square brackets is the number of possible birth orders of four boys and three 35 Answer girls. This probability works out to ⁄128. Likewise, the (a) Because the phenotypically normal parents have an probability that the sibship consists of three boys and four 1 3 1 4 35 affected son who gets his only X chromosome from girls is [7!/(3!4!)]( ⁄2) ( ⁄2) , which also equals ⁄128. The ©his Jones mother, the& Bartlett mother must Learning, be a carrier LLC of the muta- question asks© Jones for the probability& Bartlett of Learning,either four boys LLC and tion. Therefore, the probability that any particular three girls or three boys and four girls, and these events NOT FOR SALE OR1 DISTRIBUTION NOT FOR SALE OR DISTRIBUTION daughter is a carrier is ⁄2. The probability that all are mutually exclusive; hence the overall probability is 1 3 35 35 35 three daughters are carriers is ( ⁄2) because their ⁄128 ⁄128 ⁄64, or about 55%. births are independent events. (b) If the daughter is not a carrier, the probability of an A geneticist carries out a cross between two strains affected son is 0; and if the daughter is a carrier, the of fruit flies that are heterozygous for a recessive allele of © Jones & Bartlett Learning, LLC 1 © Jones & Bartlett Learning, LLC probability of an affected son is ⁄2. Because the prob- each of two genes, st (scarlet) and bw (brown), affecting eye 1 NOT FOR SALEability OR of theDISTRIBUTION daughter being a carrier is ⁄2 (part a),NOT color.FOR Flies SALE homozygous OR DISTRIBUTION for st have bright red (scarlet) eyes,

148 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 148 4/27/11 9:33 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FORwhereas SALE st OR/st andDISTRIBUTION st/st genotypes have wildtype brick-redNOT whereFOR theSALE sum isOR over DISTRIBUTION all classes of progeny. In this case,

eyes. Flies homozygous for bw have brown eyes, whereas 2 2 2 2 (150 135) (36 45) (46 45) (8 15) bw/ bw and bw/ b genotypes have wildtype brick-red 2 eyes. The double homozygous genotype st/st; bw/bw results 135 45 45 15 in white eyes. In a test of independent assortment of these 6.76 two genes, a geneticist© crosses Jones st/ st&; bwBartlett/bw females Learning, with LLC © Jones & Bartlett Learning, LLC st/st; bw/bw males. AmongNOT 240 FOR progeny SALE there OR are 150DISTRIBUTION flies (c) The number of degrees ofNOT freedom FOR equals SALE the number OR DISTRIBUTIONof with wildtype eyes, 36 with scarlet eyes, 46 with brown classes of data minus 1. In this case there are four classes eyes, and 8 with white eyes. of data; thus there are three degrees of freedom. (a) Under the null hypothesis that these genes undergo (d) The P-value for a chi-square value of 6.76 with independent assortment, what are the expected 3 degrees of freedom equals 0.08. This P-value is numbers© Jones in each& Bartlett phenotypic Learning, class? LLC greater© than Jones 0.05. &Therefore, Bartlett we Learning, should not reject LLC the (b) What is the value of the chi-square in a test of good- null hypothesis of independent assortment. nessNOT of FOR fit between SALE theOR observed DISTRIBUTION values and the (e) A greaterNOT chi-square FOR SALE value OR would DISTRIBUTION decrease the expected values based on the null hypothesis of inde- P-value. pendent assortment? (c) How many degrees of freedom does this chi-square The mutation for bar-shaped eyes in Drosophila value have? melanogaster shows the following features of genetic © Jones &(d) Bartlett What is theLearning, P-value for LLC the chi-square value in this© Jonestransmission: & Bartlett Learning, LLC NOT FOR SALEgoodness-of-fit OR DISTRIBUTION test? Does this P-value support theNOT (a)FOR The SALE mating OR of bar-eyed DISTRIBUTION males with wildtype females null hypothesis of independent assortment or should produces wildtype sons and bar-eyed daughters. the hypothesis be rejected? (b) The bar-eyed females from the mating in part a, (e) Would a greater chi-square value increase or decrease when mated with wildtype males, yield a 1 : 1 ratio the P-value? of bar : wildtype sons and a 1 : 1 ratio of bar : wildtype © Jones & Bartlett Learning, LLC daughters. © Jones & Bartlett Learning, LLC Answer What mode of inheritance do these characteristics (a) Because this is a dihybridNOT FOR cross SALE st /st; bw OR/bw DISTRIBUTION st / suggest? NOT FOR SALE OR DISTRIBUTION st; bw/bw, the ratio of 9 : 3 : 3 : 1 of the offspring phenotypes should be expected if the genes assort Answer Because the sexes are affected unequally in the prog- independently. We can calculate the expected num- eny of the mating in a, some association with the sex chro- ber of flies in each class of the progeny: mosomes is suggested. The progeny from mating a provide Phenotype© Jones Progeny& Bartlett Learning, Expected number LLC the important© Jonesclue. Because & Bartlett a male receives Learning, his X-chromo- LLC some from his mother, then the observation that all males wildtype st/–; bw/– (9/16) 240 135 NOT FOR SALE OR DISTRIBUTION are wildtypeNOT suggests FOR that SALE the gene OR for DISTRIBUTION bar eyes is on the scarlet st/st; bw /– (3/16) 240 45 X-chromosome. The fact that all daughters are affected is brown st /–; bw/bw (3/16) 240 45 also consistent with X-linkage, provided that the bar muta- white st/st; bw/bw (1/16) 240 15 tion is dominant. Mating b confirms the hypothesis of a dominant X-linked gene, because the females from a mat- © Jones &(b) BartlettThe chi-square Learning, is calculated LLC as © Jonesing a would& Bartlett have the Learning, genotype bar /LLC and so would produce NOT FOR SALE OR DISTRIBUTION(observed - expected)2 NOT theFOR observed SALE progeny. OR DISTRIBUTION The data are therefore consistent 2 ∑ with the bar mutation being an X-linked dominant. expected

© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 4.1 The diagrams belowNOT illustrate FOR aSALE pair of ORhomologous DISTRIBUTION 4.2 The diagrams below illustrateNOT FORanaphase SALE in an ORorgan- DISTRIBUTION chromosomes in prophase I of meiosis. Which dia- ism that has two pairs of homologous chromosomes. gram corresponds to each stage: leptotene, zygotene, Identify the stages as mitosis, meiosis I, or meiosis II. pachytene, diplotene, and diakinesis? (A) (B) (C) (A) (B) (C) © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4.3 What is the probability that four offspring from the mating Aa Aa consist of exactly 3 A and 1 aa? (D) (E) 4.4 A woman who is heterozygous for both a phenylketonuria mutation and an X-linked hemophilia muta- © Jones & Bartlett Learning, LLC © Jones tion& Bartlett has a child Learning, with a phenotypically LLC normal man NOT FOR SALE OR DISTRIBUTION NOT FORwho SALE is also OR heterozygous DISTRIBUTION for a phenylketonuria

Analysis and Applications 149

26105_CH04_116_153.indd 149 4/27/11 9:33 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE mutation. OR DISTRIBUTIONWhat is the probability that the child will bulbs. When seeds resulting from self-fertilization be affected by both diseases? (Assume that they are of the F1 plants were grown, onion bulbs were equally likely to have a boy or a girl.) recovered in the ratio of 12 white bulbs : 3 red bulbs 4.5 In the accompanying pedigree the purple symbols : 1 yellow bulb. Propose a hypothesis to explain represent individuals affected with X-linked Du- these observations. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC chenne muscular dystrophy. What is the probability 4.13 Among 160 progeny in the F2 generation of a dihy- that the woman III-3NOT is aFOR heterozygous SALE ORcarrier? DISTRIBUTIONbrid cross, a geneticist NOTobserves FOR four SALEdistinct ORpheno- DISTRIBUTION I types in the ratio 91: 21 : 37 : 11. She believes this 12 result may be consistent with a ratio of 9 : 3 : 3 : 1. To test this hypothesis, she calculates the chi-square II value. Does the test support her hypothesis, or 3 © Jones & Bartlett12 Learning,4 LLC should© she Jones reject &it? Bartlett Learning, LLC NOT FORIII SALE OR DISTRIBUTION 4.14 What NOTis the FORvalue ofSALE the chi-square OR DISTRIBUTION that tests good- 123 45 ness of fit between the observed numbers 40 : 60 as 4.6 A chromosomally normal woman and a chromosom- compared with the expected numbers 50 : 50? ally normal man have a son whose sex-chromosome 4.15 What is the probability that a sibship of seven chil- constitution is XYY. In which parent, and in which dren includes at least one boy and at least one girl? Assume that a sex ratio is 1 : 1. © Jones & Bartlettmeiotic division,Learning, did the LLC nondisjunction take place?© Jones & Bartlett Learning, LLC 4.7 Drosophila virilis is a diploid organism with 6 pairs of 4.16 How many genotypes are possible for an autosomal NOT FOR SALEchromosomes OR DISTRIBUTION (12 chromosomes altogether). HowNOT FORgene SALE with ORsix alleles? DISTRIBUTION How many genotypes are pos- many chromatids and chromosomes are present in sible with an X-linked gene with six alleles? the following stages of cell division: 4.17 The growth habit of the Virginia groundnut Arachis (a) Metaphase of mitosis? hypogaea can be “runner“ (spreading) or “bunch“ (b) Metaphase I of meiosis? (compact). Two pure-breeding strains of groundnuts (c) Metaphase II© of Jonesmeiosis? & Bartlett Learning, LLC with the bunch growth© Joneshabit are & crossed. Bartlett The Learning, F1 LLC 4.8 In a trihybrid crossNOT with genesFOR thatSALE undergo OR indepen- DISTRIBUTIONplants have the runner NOTgrowth FOR habit. SALE If the plants OR are DISTRIBUTION dent assortment: allowed to self-fertilize, the F2 progeny ratio is 9 run- (a) What is the expected proportion of triply hetero- ner: 7 bunch. What genetic hypothesis can account for these observations? zygous offspring in the F2 generation? (b) What is the expected proportion of triply homo- 4.18 In some human pedigrees, the blue/brown eye color variation segregates like a single-gene difference with zygous offspring in the F2 generation? 4.9 © The Jones diploid & gekkonid Bartlett lizard Learning, Gonatodes LLC taniae from the brown© Jones allele &dominant Bartlett to Learning,the blue allele. LLC Two NOTVenezuela FOR has SALE a somatic OR chromosome DISTRIBUTION number of 16. brown-eyedNOT FOR individuals SALE each OR of DISTRIBUTIONwhom had a blue- If the centromeres of the 8 homologous pairs are des- eyed parent mate. Assuming that the trait segregates ignated as Aa, Bb, Cc, Dd, Ee, Ff, Gg, and Hh: like a single-gene difference in this pedigree: (a) How many different combinations of centro- (a) What is the probability that the first child will meres could be produced during meiosis? have brown eyes? © Jones & Bartlett(b) What Learning, is the probability LLC that a gamete will contain© Jones (b)& Bartlett If a brown-eyed Learning, child results, LLC what is the prob- only those centromeres designated by capital ability that the child will be heterozygous? NOT FOR SALE letters?OR DISTRIBUTION NOT FOR(c) SALE What isOR the DISTRIBUTION probability that this couple will have 4.10 Among sibships consisting of six children, and assum- three children with blue eyes? That none of the ing a sex ratio of 1 : 1: three children will have blue eyes? (a) What is the proportion with no girls? 4.19 In the pedigree below, the male I-2 is affected with red- (b) What is the proportion with exactly one girl? green color blindness owing to an X-linked mutation. (c) What is the proportion© Jones with & Bartlett exactly two Learning, girls? LLC What is the probability ©that Jones male IV-1 & Bartlettis color blind? Learning, LLC (d) What is the proportionNOT FOR with SALE exactly OR three DISTRIBUTION girls? (Assume that the only possibleNOT sourceFOR of SALE the color OR blind- DISTRIBUTION (e) What is the proportion with three or more boys? ness mutation in the pedigree is that from male I-2.) 4.11 A litter of cats includes eight kittens. What is the I probability that it contains an even number each of 12 males and females? Assume an equal likelihood of ©male Jones and female & Bartlett kittens, Learning, and for purposes LLC of this © JonesII & Bartlett Learning, LLC problem regard 0 as an even number. Does the 1234 5 NOTanswer FOR surprise SALE you? ORWhy? DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4.12 A horticulturalist crossed a true-breeding onion III 12 3 4 plant with red bulbs to a true-breeding onion plant with white bulbs. All of the F plants had white IV ? 1 1 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

150 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 150 4/27/11 9:33 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR4.20 SALE The male OR II-1DISTRIBUTION in the pedigree shown here is affected (a) yellow male wildtype female with a trait due to a rare X-linked recessive allele. Use (b) yellow female wildtype male the principles of conditional probability to calculate (c) daughter from mating in part a wildtype male the probability that the female III-1 is a heterozygous (d) daughter from mating in part a yellow male carrier. 4.24 The accompanying pedigree and gel diagram show © Jones & Bartlett Learning, LLC the molecular phenotypes© Jones for an & RFLP Bartlett with twoLearning, LLC I NOT12 FOR SALE OR DISTRIBUTIONalleles. What mode of inheritanceNOT FOR does SALE the pedigree OR DISTRIBUTION suggest? Based on this hypothesis, and using A1 to II represent the RFLP allele associated with the 3-kb 12 3 band and A2 to represent that associated with the III 8-kb band, deduce the genotype of each individual in © Jones & Bartlett Learning,12 LLC the pedigree.© Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FORI-1 SALEI-2 OR DISTRIBUTION IV 1 2 3 4.21 The pedigree shown below is the same as that in II-1 II-2 II-3 II-4 II-5 II-6 Problem 4.20 but with additional information based on molecular analysis. The male II-1 is again affected III-1 III-2 III-3 III-4 © Jones & Bartlettwith a trait Learning, due to a rare LLC X-linked recessive allele. The© Jones & Bartlett Learning, LLC NOT FOR SALEbands OR in the DISTRIBUTION gel are restriction fragments that identifyNOT FOR SALE OR DISTRIBUTION 12 kb the wildtype allele (the shorter fragment S corre- 9kb sponding to the band near the bottom of the gel) or the mutant allele (the longer fragment L correspond- 6kb ing to the band near the top of the gel). From the information given© in Jones the pedigree & Bartlett and the Learning,gels, cal- LLC © Jones & Bartlett 3kbLearning, LLC culate the probabilityNOT that FOR the SALEfemale III-1OR isDISTRIBUTION a het- NOT FOR SALE OR DISTRIBUTION erozygous carrier. 1kb

L 4.25 Tall, yellow-flowered crocus is mated with short, I S 12S white-flowered crocus. Both varieties are true breeding. All the F1 plants are backcrossed with the short, © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC II L white-flowered variety. This backcross yielded 800 NOT FOR SALE12 OR DISTRIBUTION3 S progenyNOT in theFOR proportions SALE OR234 tallDISTRIBUTION yellow, 203 tall white, 175 short yellow, and 188 short white plants. III 12S Does the observed result fit the genetic hypothesis of 1 : 1 : 1 : 1 segregation as assessed by a 2 test? 4.26 IV Attached-X chromosomes in Drosophila are formed 1 2 3 from two X chromosomes attached to a common cen- © Jones & Bartlett Learning, LLC © Jones tromere.& Bartlett Females Learning, of genotype LLC C(1)RM/Y, in which NOT FOR SALE OR DISTRIBUTION NOT FORC(1)RM SALE denotes OR DISTRIBUTION the attached-X chromosomes, pro- S duce C(1)RM-bearing and Y-bearing gametes in 4.22 In the pedigree shown here, the males I-2 and III-2 equal proportions. What progeny is expected to result are affected with a trait due to a common X-linked from the mating between a male carrying the recessive allele. What is the probability that individ- X-linked allele, y, for yellow body and an attached-X ual III-1 is heterozygous?© Jones & Bartlett Learning, LLC female with wildtype body?© Jones How does & Bartlettthis result dif-Learning, LLC I NOT FOR SALE OR DISTRIBUTIONfer from the typical patternNOT of FORX-linked SALE inheritance? OR DISTRIBUTION 12 (Note: Drosophila zygotes containing three X chromo- II somes or no X chromosomes do not survive.) 12 4.27 A rare dominant autosomal mutation W results in wooly, curled hair in some European pedigrees. A III 12 woman with wooly hair with blood group O marries © Jones & Bartlett Learning, LLC a man© with Jones straight & hairBartlett (ww) withLearning, blood group LLC AB. NOT FOR SALEIV OR DISTRIBUTION The genesNOT are FOR in different SALE chromosomes. OR DISTRIBUTION 1 2 3 (a) What are the chances that the mating will pro- 4.23 Yellow body color in Drosophila is determined by the duce a wooly-haired group B child? recessive allele y of an X-linked gene, and the wild- (b) What are the chances that the mating will pro- type gray body color is determined by the y allele. duce a straight-haired group B child? © Jones & BartlettWhat genotype Learning, and LLCphenotype ratios would be© Jones (c)& Bartlett If three straight-haired Learning, children LLC with blood group NOT FOR SALEexpected OR fromDISTRIBUTION the following crosses? NOT FOR SALEA children OR DISTRIBUTIONare born to these parents, what are

Analysis and Applications 151

26105_CH04_116_153.indd 151 4/27/11 9:33 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALEthe OR chances DISTRIBUTION that the next child born will be roan colored, an intermediate color in which white wooly-haired and blood group B? hairs are intermixed with red hairs. H and R undergo 4.28 Ducklings of the domesticated mallard Anas platyrhyn- independent assortment. chos may exhibit dark brown dorsal plumage known (a) What would be the phenotype of an F1 offspring as mallard, almost black dorsal plumage known as from the mating RR HH rr hh? dusky, or a pattern© knownJones as &restricted Bartlett in whichLearning, the LLC (b) What would be ©the Jones phenotypes & Bartlett and their Learning, LLC black is confinedNOT to patches FOR on SALE the head OR and DISTRIBUTION tail. expected proportionsNOT in FORthe F2 SALEprogeny OR of the DISTRIBUTION These phenotypes result from the action of three cross F1 F1 from part a? alleles of a single autosomal gene. Three types of (c) What would be the phenotypes and their crosses were made, with the following results: expected proportions among the progeny derived 1. Restricted mallard: all F1 are restricted; crosses from crossing F1 individuals from part a to the ©of Jones F1 F 1& yield Bartlett an F2 generation Learning, with LLC the ratio 3 original© Jones horned & whiteBartlett stock? Learning, LLC NOTrestricted FOR : 1SALE mallard. OR DISTRIBUTION 4.30 FamilialNOT Mediterranean FOR SALE fever OR (FMF) DISTRIBUTION is a hereditary 2. Mallard dusky: all F1 are mallard; crosses of F1 inflammatory disorder that affects groups of patients F1 produce an F2 generation with the ratio 3 mal- originating from around the Mediterranean Sea, lard : 1 dusky. especially Armenian and non-Ashkenazi Jewish pop- 3. Restricted dusky: all F1 are restricted; crosses of ulations, Anatolian Turks, and Levantine Arabs. FMF F1 F1 produce an F2 generation with the ratio 3 is inherited as an autosomal recessive. It is not known © Jones & Bartlettrestricted Learning, : 1 dusky. LLC © Jones whether& Bartlett the geneLearning, causing LLCthe disease is the same NOT FOR SALE(a) AssumeOR DISTRIBUTION that an F1 male from cross 1 is mated withNOT FORin SALEthese different OR DISTRIBUTION populations. To investigate this an F1 female from cross 2. List the phenotypes and possibility, linkage of the allele to a series of VNTR their expected frequencies among the progeny of (variable number of tandem repeat) polymorphisms this cross. was examined. One VNTR in chromosome 16 was (b) Assume that an F1 male from cross 3 is mated with especially informative. For this VNTR, two extended an F1 female from© Jones cross 2. &List Bartlett the phenotypes Learning, and LLC Armenian families from© the Jones same geographic& Bartlett region Learning, LLC their expected frequencies among the progeny of gave the results shown in the accompanying pedi- this cross. NOT FOR SALE OR DISTRIBUTIONgrees and gels. The greenNOT symbols FOR represent SALE affectedOR DISTRIBUTION 4.29 In cattle, an allele for the absence of horns shows individuals. The numbers between the gels corre- complete dominance: HH and Hh are hornless or spond to the VNTR alleles. polled, and hh is horned. On the other hand, the (a) Is there evidence for linkage of the allele for FMF effect of the allele producing red coat (R) shows to any VNTR allele? ©incomplete Jones &dominance Bartlett withLearning, the allele LLC producing (b) Do© any Jones of the data& Bartlett conflict with Learning, your explanation? LLC NOTwhite coatFOR color SALE (r). The OR heterozygous DISTRIBUTION genotype Rr is IfNOT so, how FOR do you SALE account OR for DISTRIBUTIONit?

1 10 11 21 © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 23456789 12 13 14 15 16 17 18 19 20

4 3 © Jones & Bartlett Learning,2 LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION1 NOT FOR SALE OR DISTRIBUTION

152 CHAPTER 4 Chromosomes and Sex-Chromosome Inheritance

26105_CH04_116_153.indd 152 4/27/11 9:33 AM © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION The accompanying pedigree and gel dia- In mice, the dominant T allele results in a gram pertain to a morphological phenotype (green short tail, but the homozygous T/T genotype is lethal. symbols in the pedigree) and a molecular phenotype (a A cross between two short-tailed mice produces a lit- two-allele RFLP). What mode of inheritance do these ter of five pups. What is the expected distribution of data suggest for each© Jonestrait? & Bartlett Learning, LLCtailless to tailed mice? Why© Jones are the & two Bartlett most likely Learning, LLC

I-1NOT FORI-2 SALE OR DISTRIBUTIONoutcomes equally probable?NOT FOR SALE OR DISTRIBUTION

X-linked hemophilia is present in the pedigree illustrated here with red symbols. What is II-1 II-2 II-3 II-4 II-5 II-6 the probability that the woman III-5 is a carrier, tak- III©-1 JonesIII-2 & Bartlett Learning,III-3 III LLC-4 ing into© account Jones the & information Bartlett Learning,that she has had LLC two normal sons? What is the probability that her next son NOT FOR SALE OR DISTRIBUTION will beNOT affected? FOR SALE OR DISTRIBUTION 12 kb 9kb I 12 6kb II © Jones & Bartlett Learning, LLC 3kb© Jones & Bartlett12 Learning,3 4 LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 1kb III 123 45 6

IV © Jones & Bartlett Learning, LLC © Jones1 2 & Bartlett34 Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION GENETICS on the web GeNETics on the Web will introduce you to some of the most important sites for finding genetics information on the Internet. To explore these sites, visit the Jones & Bartlett companion site to accompany Genetics: Analysis© Jones of Genes and & Genomes, Bartlett Eighth Learning, Edition at http://biology.jbpub LLC © Jones & Bartlett Learning, LLC .com/book/genetics/8e/.NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION There you will find a chapter-by-chapter list of highlighted keywords. When you select one of the keywords, you will be linked to a Web site containing information related to that keyword. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION

Challenge Problems 153

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