Patterns of Inheritance                     Concept Outline       Mendel solved the mystery of heredity.Early Ideas about ...
heredity.Early Ideas about Heredity:The Road to MendelAs far back as written records go, patterns of resemblanceamong the ...
This idea was predominant until fairly                                               It is worth repeating that the offspr...
Mendel and the Garden PeaThe first quantitative studies of inheritance were carriedout by Gregor Mendel, an Austrian monk ...
Mendels Experimental DesignMendel was careful to focus on only a few specific differ-                                     ...
What Mendel Found                                                          intermediate color, as the theory of blending i...
The ¥2 Generation  After allowing individual FI plants to mature and self-  pollinate, Mendel collected and planted the se...
Mendels Model of HeredityFrom his experiments, Mendel was able to understand fourthings about the nature of heredity. Firs...
How Mendel Interpreted His Results                                    flower color. The dominant allele is written in uppe...
The FI GenerationUsing these simple symbols, we can now go back and reex-amine the crosses Mendel carried out. Since a whi...
The Testcross                                                           To perform his testcross, Mendel crossed heterozyg...
Mendels Second Law of Heredity:Independent AssortmentAfter Mendel had demonstrated that different alleles of agiven gene s...
Mendelian Inheritance Is Not                                             White Always Easy to AnalyzeMendels original pape...
Continuous VariationFew phenotypes are the result of the actionof only one gene. Instead, most traits reflectthe action of...
Lack of Complete Dominance                                                                                        Sperm No...
13.2        .                               are on chromes                 . • .-.-. -Chromosomes: The Vehiclesof Mendelia...
Y chromosome              X chromosome with               X chromosome with                                               ...
Genetic Recombination                                                                   The chromosomal exchanges Stern de...
Using Recombination to Make Genetic Maps                              Chromosome                        Location of genes ...
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
Patterns of inheritance
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Patterns of inheritance

  1. 1. Patterns of Inheritance Concept Outline Mendel solved the mystery of heredity.Early Ideas about Heredity: The Road to Mendel. Before Mendel, biologists believed in the direct transmission of traits.Mendel and the Garden Pea. Mendel, a monk, experimented with heredity in edible peas, as had many others, but he counted his results.What Mendel Found. Mendel found that contrasting traits segregated among second-generation progeny in the ratio 3:1.Mendels Model of Heredity. Mendel proposed that information rather than the trait itself is inherited, with each parent contributing one copy.How Mendel Interpreted His Results. Mendel found that one alternative of a trait could mask the other in heterozygotes, but both could subsequently be expressed in homozygotes of future generations.Mendelian Inheritance Is Not Always Easy to Analyze. A variety of factors can disguise the Mendelian segregation of alleles. „ Genes are on chromosomes.Chromosomes: The Vehicles of Mendelian Inheritance. FIGURE 13.1 Mendelian segregation reflects the random assortment of Human beings are extremely diverse in appearance. The chromosomes in meiosis. differences between us are partly inherited and partly the result of environmental factors we encounter in our lives.Genetic Recombination. Crossover frequency indicates the physical distance between genes and is used to construct genetic maps. 13.3 Human genetics follows Mendelian principles. E very living creature is a product of the long evolution- ary history of life on earth. While all organisms share this history, only humans wonder about the processes thatMultiple Alleles: The ABO Blood Groups. The human ABO blood groups are determined by three / gene alleles. led to their origin. We are still far from understandingHuman Chromosomes. Humans possess 2 3 pairs of everything about our origins, but we have learned a great chromosomes, one of them determining the sex. deal. Like a partially completed jigsaw puzzle, the bound-Human Abnormalities Due to Alterations in Chromosome aries have fallen into place, and much of the internal struc- Number. Loss or addition of chromosomes has serious ture is becoming apparent. In this chapter, we will discuss consequences. one piece of the puzzle—the enigma of heredity. Why doHuman Genetic Disorders. Many heritable human disorders groups of people from different parts of the world often are the result of recessive mutations in genes. differ in appearance (figure 13.1)? Why do the members ofGenetic Counseling. Some gene defects can be detected early a family tend to resemble one another more than they re- in pregnancy. semble members of other families? 241
  2. 2. heredity.Early Ideas about Heredity:The Road to MendelAs far back as written records go, patterns of resemblanceamong the members of particular families have been notedand commented on (figure 13.2). Some familial features areunusual, such as the protruding lower lip of the Europeanroyal family Hapsburg, evident in pictures and descriptionsof family members from the thirteenth century onward.Other characteristics, like the occurrence of redheadedchildren within families of redheaded parents, are morecommon (figure 13.3). Inherited features, the buildingblocks of evolution, will be our concern in this chapter. Like many great puzzles, the riddle of heredity seemssimple now that it has been solved. The solution was not aneasy one to find, however. Our present understanding isthe culmination of a long history of thought, surmise, andinvestigation. At every stage we have learned more, and aswe have done so, the models we use to describe the mecha-nisms of heredity have changed to encompass new facts. FIGURE 13.2 Heredity is responsible for family resemblance. FamilyClassical Assumption 1: Constancy of Species resemblances are often strong—a .visual manifestation of theTwo concepts provided the basis for most of the thinking mechanism of heredity. This is the Johnson family, the wife and daughters of one of the authors. While each daughter is different,about heredity before the twentieth century. The first is all clearly resemble their mother.that heredity occurs within species. For a very long time peo-ple believed that it was possible to obtain bizarre compos-ite animals by breeding (crossing) widely different species.The minotaur of Cretan mythology, a creature with thebody of a bull and the torso and head of a man, is one ex-ample. The giraffe was thought to be another; its scientificname, Giraffa camelopardalis, suggests the belief that it wasthe result of a cross between a camel and a leopard. Fromthe Middle Ages onward, however, people discovered thatsuch extreme crosses were not possible and that variationand heredity occur mainly within the boundaries of a par-ticular species. Species were thought to have been main-tained without significant change from the time of theircreation.Classical Assumption 2: Direct Transmissionof TraitsThe second early concept related to heredity is that traitsare transmitted directly. When variation is inherited by off-spring from their parents, what is transmitted? The ancientGreeks suggested that the parents body parts were trans- FIGURE 13.3mitted directly to their offspring. Hippocrates called this Red hair is inherited. Many different traits are inherited intype of reproductive material gonos, meaning "seed." human families. This redhead is exhibiting one of these traits.Hence, a characteristic such as a misshapen limb was theresult of material that came from the misshapen limb of a from the other parts, and the child was formed after theparent. Information from each part of the body was sup- hereditary material from all parts of the parents bodies hadposedly passed along independently of the information come together.242 Part IV Reproduction and Heredity
  3. 3. This idea was predominant until fairly It is worth repeating that the offspring recently. For example, in 1868, Charles of Koelreuters crosses were not identical Darwin proposed that all cells and tissues to one another. Some resembled the hy- excrete microscopic granules, or "gem- brid generation, while others did not. The mules," that are passed to offspring, guid- alternative forms of the traits Koelreuter ing the growth of the corresponding part in was studying were distributed among the the developing embryo. Most similar theo- offspring. A modern geneticist would say ries of the direct transmission of hereditary the alternative forms of each trait were material assumed that the male and female segregating among the progeny of a mat- contributions blend in the offspring. Thus, ing, meaning that some offspring exhibited parents with red and brown hair would one alternative form of a trait (for example, produce children with reddish brown hair, hairy leaves), while other offspring from and tall and short parents would produce the same mating exhibited a different alter- children of intermediate height. native (smooth leaves). This segregation of alternative forms of a trait provided the clue that led Gregor Mendel to his under-Koelreuter Demonstrates standing of the nature of heredity.Hybridization between Species Taken together, however, these two con- Knight Studies Heredity in Peas cepts lead to a paradox. If no variation en- ters a species from outside, and if the varia- Over the next hundred years, other investi- tion within each species blends in every gators elaborated on Koelreuters work. generation, then all members of a species FIGURE 13.4 Prominent among them were English gen- should soon resemble one another exactly. The garden pea, Pimm tleman farmers trying to improve varieties Obviously, this does not happen. Individu- sativum. Easy to cultivate and of agricultural plants. In one such series of als within most species differ widely from able to produce many distinctive experiments, carried out in the 1790s, each other, and they differ in characteristics varieties, the garden pea was a T. A. Knight crossed two true-breeding that are transmitted from generation to popular experimental subject in varieties (varieties that remain uniform generation. investigations of heredity as long from one generation to the next) of the How could this paradox be resolved? Ac- as a century before Gregor garden pea, Pisum sativum (figure 13.4). Mendels experiments. tually, the resolution had been provided One of these varieties had purple flowers, long before Darwin, in the work of the and the other had white flowers. All of the German botanist Josef Koelreuter. In 1760, progeny of the cross had purple flowers.Koelreuter carried out the first successful hybridizations Among the offspring of these hybrids, however, were some of plant species, crossing different strains of tobacco and plants with purple flowers and others, less common, withobtaining fertile offspring. The hybrids differed in appear- white flowers. Just as in Koelreuters earlier studies, a traitance from both parent strains. When individuals within the from one of the parents disappeared in one generationhybrid generation were crossed, the offspring were highly only to reappear in the next.variable. Some of these offspring resembled plants of the In these deceptively simple results were the makings of ahybrid generation (their parents), but a few resembled the scientific revolution. Nevertheless, another century passedoriginal strains (their grandparents). before the process of gene segregation was fully appreci- ated. Why did it take so long? One reason was that earlyThe Classical Assumptions Fail workers did not quantify their results. A numerical record of results proved to be crucial to understanding the process.Koelreuters work represents the beginning of modern Knight and later experimenters who carried out othergenetics, the first clues pointing to the modern theory of crosses with pea plants noted that some traits had aheredity. Koelreuters experiments provided an impor- "stronger tendency1" to appear than others, but they did nottant clue about how heredity works: the traits he was record the numbers of the different classes of progeny. Sci-studying could be masked in one generation, only to ence was young then, and it was not obvious that the num-reappear in the next. This pattern contradicts the theory bers were important.of direct transmission. How could a trait that is transmit-ted directly be latent and then reappear? Nor were the Early geneticists demonstrated that some forms oftraits of Koelreuters plants blended. A contemporary ac- an inherited trait (1) can disappear in one generationcount stated that the traits reappeared in the third gener- only to reappear unchanged in future generations;ation "fully restored to all their original powers and (2) segregate among the offspring of a cross; and (3) are more likely to be represented than their" Chapter 13 Patterns of Inheritance 243
  4. 4. Mendel and the Garden PeaThe first quantitative studies of inheritance were carriedout by Gregor Mendel, an Austrian monk (figure 13.5).Born in 1822 to peasant parents, Mendel was educated in amonastery and went on to study science and mathematicsat the University of Vienna, where he failed his examina-tions for a teaching certificate. He returned to themonastery and spent the rest of his life there, eventuallybecoming abbot. In the garden of the monastery, Mendelinitiated a series of experiments on plant hybridization (fig-ure 13.6). The results of these experiments would ulti-mately change our views of heredity irrevocably.Why Mendel Chose the Garden PeaFor his experiments, Mendel chose the garden pea, thesame plant Knight and many others had studied earlier.The choice was a good one for several reasons. First, manyearlier investigators had produced hybrid peas by crossingdifferent varieties. Mendel knew that he could expect toobserve segregation of traits among the offspring. Second,a large number of true-breeding varieties of peas wereavailable. Mendel initially examined 32. Then, for furtherstudy, he selected lines that differed with respect to seveneasily distinguishable traits, such as round versus wrinkledseeds and purple versus white flowers, a characteristicKnight had studied. Third, pea plants are small and easy togrow, and they have a short generation time. Thus, one canconduct experiments involving numerous plants, grow sev-eral generations in a single year, and obtain results rela-tively quickly. FIGURE 13.5 A fourth advantage of studying peas is that the sexual or- Gregor Johann Mendel. Cultivating his plants in the garden of agans of the pea are enclosed within the flower (figure 13.7). monastery in Brunn, Austria (now Brno, Czech Republic),The flowers of peas, like those of most flowering plants, con- Mendel studied how differences among varieties of peas weretain both male and female sex organs. Furthermore, the ga- inherited when the varieties were crossed. Similar experimentsmetes produced by the male and female parts of the same had been done before, but Mendel was the first to appreciate the significance of the results.flower, unlike those of many flowering plants, can fuse toform viable offspring. Fertilization takesplace automatically within an individualflower if it is not disturbed, resulting inoffspring that are the progeny from asingle individual. Therefore, one can ei-ther let individual flowers engage inself-fertilization, or remove the flow-ers male parts before fertilization andintroduce pollen from a strain with al-ternative characteristics, thus perform-ing cross-pollination which results incross-fertilization.FIGURE 13.6The garden where Mendel carried outhis plant-breeding experiments. GregorMendel did his most important scientificexperiments in this small garden in amonastery.244 Part IV Reproduction and Heredity
  5. 5. Mendels Experimental DesignMendel was careful to focus on only a few specific differ- Petalsences between the plants he was using and to ignore thecountless other differences he must have seen. He also hadthe insight to realize that the differences he selected to ana-lyze must be comparable. For example, he appreciated that Anther Strying to study the inheritance of round seeds versus tallheight would be useless; the traits, like apples and oranges,are not comparable. Mendel usually conducted his experiments in three stages: Carpel 9 1. First, he allowed pea plants of a given variety to pro- duce progeny by self-fertilization for several genera- tions. Mendel was thus able to assure himself that the forms of traits he was studying were indeed constant, transmitted unchanged from generation to genera- FIGURE 13.7 Structure of the pea flower (longitudinal section). In a pea tion. Pea plants with white flowers, for example, plant flower, the petals enclose the male anther (containing pollen when crossed with each other, produced only off- grains, which give rise to haploid sperm) and the female carpel spring with white flowers, regardless of the number (containing ovules, which give rise to haploid eggs). This ensures of generations. that self-fertilization will take place unless the flower is disturbed. 2. Mendel then performed crosses between varieties exhibiting alternative forms of traits. For example, he removed the male parts from the flower of a plant that pro- duced white flowers and fertilized it with pollen from a purple- flowered plant. He also carried out the reciprocal cross, using pollen from a white-flowered in- dividual to fertilize a flower on a pea plant that produced purple Pollen transferred from white flowers (figure 13.8). flower to stigma of purple flower Anthers 3. Finally, Mendel permitted the removed hybrid offspring produced by these crosses to self-pollinate for several generations. By doing so, he allowed the alternative forms of a trait to segregate among the progeny. This was the same ex- perimental design that Knight and others had used much earlier. But Mendel went an important step farther: he counted the num- bers of offspring of each type in each succeeding generation. No one had ever done that before. The quantitative results Mendel obtained proved to be of supreme importance in revealing the process of heredity. FIGURE 13.8 How Mendel conducted his experiments. Mendel pushed aside the petals of a white Mendels experiments with the flower and cut off the anthers, the source of the pollen. He then placed that pollen onto the garden pea involved crosses stigma (part of the carpel) of a similarly castrated purple flower, causing cross-fertilization between true-breeding varieties, to take place. All the seeds in the pod that resulted from this pollination were hybrids of the followed by a generation or more white-flowered male parent and the purple-flowered female parent. After planting these of inbreeding. seeds, Mendel observed what kinds of plants they produced. All of the progeny of this cross had purple flowers. Chapter 13 Patterns of Inheritance 245
  6. 6. What Mendel Found intermediate color, as the theory of blending inheritance would predict. Instead, in every case the flower color ofThe seven traits Mendel studied in his experiments pos- the offspring resembled one of their parents. It is custom-sessed several variants that differed from one another in ary to refer to these offspring as the first filial (filius isways that were easy to recognize and score (figure 13.9). Latin for "son"), or FI, generation. Thus, in a cross ofWe will examine in detail Mendels crosses with flower white-flowered with purple-flowered plants, the FI off-color. His experiments with other traits were similar, and spring all had purple flowers, just as Knight and othersthey produced similar results. had reported earlier. Mendel referred to the trait expressed in the FI plants as dominant and to the alternative form that was not ex-The FI Generation pressed in the FI plants as recessive. For each of theWhen Mendel crossed two contrasting varieties of peas, seven pairs of contrasting forms of traits that Mendel ex-such as white-flowered and purple-flowered plants, the amined, one of the pair proved to be dominant and thehybrid offspring he obtained did not have flowers of other recessive. Trait Dominant vs. recessive F2 generation Ratio Dominant form Recessive form Flower color 705 224 3.15:1 Purple White " Seed color O 6022 2001 3.01:1 Yellow Green Seed shape x -<• 5474 1850 2.96:1 Round Wrinkled Pod X 152 2.82:1 428 color ,„=**• Green Yellow Pod shape </ 882 299 2.95:1 Round "Constricted Flower position 651 207 3.14:1 Axial Plant height 787 277 2.84:1 Tall DwarfFIGURE 13.9Mendels experimental results. This table illustrates the seven pairs of contrasting traits Mendel studied in his crosses of the garden peaand presents the data he obtained for these crosses. Each pair of traits appeared in the p2 generation in very close to a 3:1 ratio.246 Part IV Reproduction and Heredity
  7. 7. The ¥2 Generation After allowing individual FI plants to mature and self- pollinate, Mendel collected and planted the seeds from each plant to see what the offspring in the second filial, or p2, generation would look like. He found, just as Knight had earlier, that some p2 plants exhibited white flowers, the recessive form of the trait. Latent in the FI generation, the recessive form reappeared among some ¥2 individuals. Believing the proportions of the F2 types would provide some clue about the mechanism of heredity, Mendel counted the numbers of each type among the F2 progeny. In the cross between the purple-flowered FI plants, he counted a total of 929 F2 individuals (see figure 13.9). Of these, 705 (75.9%) had purple flowers and 224 (24.1%) hadwhite flowers. Approximately /4 of the p2 individuals exhib-ited the recessive form of the trait. Mendel obtained thesame numerical result with the other six traits he examined:! / of the p2 individuals exhibited the dominant form of thetrait, and 14 displayed the recessive form. In other words,the dominant: recessive ratio among the p2 plants was al-ways close to 3:1. Mendel carried out similar experimentswith other traits, such as wrinkled versus round seeds (fig- у 97 yure 13.10), and obtained the same result. A page from Mendels notebook. In these notes, Mendel is trying various ratios in an unsuccessful attempt to explain a segregation ratio disguised by phenotypes that are so similar he cannot distinguish them from one another. A Disguised 1:2:1 Ratio Mendel went on to examine how the F2 plants passed traits on to subsequent generations. He found that the recessive К were always true-breeding. In the cross of white-flowered with purple-flowered plants, for example, the white- flowered p2 individuals reliably produced white-flowered offspring when they were allowed to self-fertilize. By con- trast, only И of the dominant purple-flowered F2 individuals (i4 of all p2 offspring) proved true-breeding, while 2A were not. This last class of plants produced dominant and reces- sive individuals in the third filial (Рз) generation in a 3:1 ratio. This result suggested that, for the entire sample, the 3:1 ratio that Mendel observed in the p2 generation was really a disguised 1:2:1 ratio: !4 pure-breeding dominant individuals, 1A not-pure-breeding dominant individuals, and 14 pure-breeding recessive individuals (figure 13.11). When Mendel crossed two contrasting varieties and counted the offspring in the subsequent generations, he found all of the offspring in the first generationFIGURE 13.10 exhibited one (dominant) trait, and none exhibited theSeed shape: a Mendelian trait. One of the differences Mendel other (recessive) trait. In the following generation, 25%studied affected the shape of pea plant seeds. In some varieties, were pure-breeding for the dominant trait, 50% werethe seeds were round, while in others, they were wrinkled. As you hybrid for the two traits and appeared dominant, andcan see, the wrinkled seeds look like dried-out versions of the 25% were pure-breeding for the recessive trait.round ones. Chapter 13 Patterns of Inheritance 247
  8. 8. Mendels Model of HeredityFrom his experiments, Mendel was able to understand fourthings about the nature of heredity. First, the plants hecrossed did not produce progeny of intermediate appear-ance, as a theory of blending inheritance would have pre-dicted. Instead, different plants inherited each alternativeintact, as a discrete characteristic that either was or was notvisible in a particular generation. Second, Mendel learnedthat for each pair of alternative forms of a trait, one alter-native was not expressed in the FI hybrids, although itreappeared in some ¥2 individuals. The "invisible" traitmust therefore be latent (present but not expressed) in theFI individuals. Third, the pairs of alternative forms of thetraits examined segregated among the progeny of a particu-lar cross, some individuals exhibiting one form of a trait,some the other. Fourth, pairs of alternatives were expressedin the ¥2 generation in the ratio of % dominant to К reces-sive. This characteristic 3:1 segregation is often referred toas the Mendelian ratio. FIGURE 13.12 To explain these results, Mendel proposed a simple A recessive trait. Blue eyes are considered a recessive trait inmodel. It has become one of the most famous models in the humans, although many genes influence eye color.history of science, containing simple assumptions and mak-ing clear predictions. The model has five elements: 4. The two alleles, one contributed by the male gamete 1. Parents do not transmit physiological traits directly to and one by the female, do not influence each other in their offspring. Rather, they transmit discrete infor- any way. In the cells that develop within the new in- mation about the traits, what Mendel called "factors." dividual, these alleles remain discrete. They neither These factors later act in the offspring to produce the blend with nor alter each other. (Mendel referred to trait. In modern terms, we would say that information them as "uncontaminated.") Thus, when the individ- about the alternative forms of traits that an individual ual matures and produces its own gametes, the alleles expresses is encoded by the factors that it receives from for each gene segregate randomly into these gametes, its parents. as described in point 2. 2. Each individual receives two factors that may code for 5. The presence of a particular allele does not ensure mat the same form or for two alternative forms of the trait. the form of the trait encoded by it will be expressed in We now know that there are two factors for each trait an individual carrying that allele. In heterozygous indi- present in each individual because these factors are car- viduals, only one allele (the dominant one) is ex- ried on chromosomes, and each adult individual is pressed, while the other (recessive) allele is present but diploid. When the individual forms gametes (eggs or unexpressed. To distinguish between the presence of sperm), they contain only one of each kind of chromo- an allele and its expression, modern geneticists refer to some; the gametes are haploid. Therefore, only one fac- the totality of alleles that an individual contains as the tor for each trait of the adult organism is contained in individuals genotype and to the physical appearance the gamete. Which of the two factors for each trait of that individual as its phenotype. The phenotype of ends up in a particular gamete is randomly determined. an individual is the observable outward manifestation 3. Not all copies of a factor are identical. In modern of its genotype, the result of the functioning of the en- terms, the alternative forms of a factor, leading to alter- zymes and proteins encoded by the genes it carries. In native forms of a trait, are called alleles. When two other words, the genotype is the blueprint, and the haploid gametes containing exactly the same allele of a phenotype is the visible outcome. factor fuse during fertilization to form a zygote, the off- spring that develops from that zygote is said to be ho- These five elements, taken together, constitute Mendels mozygous; when the two haploid gametes contain dif- model of the hereditary process. Many traits in humans ferent alleles, the individual offspring is heterozygous. also exhibit dominant or recessive inheritance, similar to In modern terminology, Mendels factors are called the traits Mendel studied in peas (figure 13.12, table 13.1). genes. We now know that each gene is composed of a particular DNA nucleotide sequence (chapter 3). The The genes that an individual has are referred to as its genotype; the outward appearance of the individual is particular location of a gene on a chromosome is re- referred to as its phenotype. ferred to as the genes locus (plural, loci).248 Part IV Reproduction and Heredity
  9. 9. How Mendel Interpreted His Results flower color. The dominant allele is written in upper case, as P; the recessive allele (white flower color) is assigned the Does Mendels model predict the results he actually ob- same symbol in lower case, p. tained? To test his model, Mendel first expressed it in In this system, the genotype of an individual that is terms of a simple set of symbols, and then used the symbols true-breeding for the recessive white-flowered trait to interpret his results. It is very instructive to do the same. would be designated pp. In such an individual, both Consider again Mendels cross of purple-flowered with copies of the allele specify the white-flowered phenotype. white-flowered plants. We will assign the symbol P to the Similarly, the genotype of a true-breeding purple-flowered dominant allele, associated with the production of purple individual would be designated PP, and a heterozygote flowers, and the symbol p to the recessive allele, associated would be designated Pp (dominant allele first). Using with the production of white flowers. By convention, ge- these conventions, and denoting a cross between two netic traits are usually assigned a letter symbol referring to strains with x, we can symbolize Mendels original cross their more common forms, in this case "P" for purple as pp x PP (figure 13.13). White Purple (PP) , (Pp) Pp Pp PP Pp Purple Purple Pp PP (PP) generation (PP) F2 generationFIGURE 13.13Mendels cross of pea plants differing in flower color. All of the offspring of the first cross (the FI generation) are Pp heterozygoteswith purple flowers. When two heterozygous FI individuals are crossed, three kinds of ¥2 offspring are possible: PP homozygotes (purpleflowers); Pp heterozygotes (also purple flowers); andpp homozygotes (white flowers). Therefore, in the p2 generation, the ratio ofdominant to recessive type is 3:1. Table Ш Recessive Traits Phenotypes Dominant Traits Phenotypes Common baldness M-shaped hairline receding with Middigital hair Presence of hair on middle age segment of fingers Albinism Lack of melanin pigmentation Brachydactyly Short fingers Alkaptonuria Inability to metabolize Huntingtons disease Degeneration of nervous homogenistic acid system, starting in middle age Red-green color Inability to distinguish red or Phenylthiocarbamide (PTC) Ability to taste PTC as bitter blindness green wavelengths of light sensitivity Cystic fibrosis Abnormal gland secretion, Camptodactyly Inability to straighten the leading to liver degeneration and little finger lung failure Hypercholesterolemia (the most Elevated levels of blood Duchenne muscular Wasting away of muscles during common human Mendelian cholesterol and risk of heart dystrophy childhood disorder—1:500) attack Hemophilia Inability to form blood clots Polydactyly Extra fingers and toes Sickle cell anemia Defective hemoglobin that causes red blood cells to curve and stick together Chapter 13 Patterns of Inheritance 249
  10. 10. The FI GenerationUsing these simple symbols, we can now go back and reex-amine the crosses Mendel carried out. Since a white-floweredparent (fp) can produce only p gametes, and a pure purple-flowered (homozygous dominant) parent (PP) can produceonly P gametes, the union of an egg and a sperm fromthese parents can produce only heterozygous Pp offspringin the FI generation (see figure 13.13). Because the P alleleis dominant, all of these FI individuals are expected tohave purple flowers. The p allele is present in these het-erozygous individuals, but it is not phenotypically ex-pressed. This is the basis for the latency Mendel saw in re-cessive traits.The РЗ GenerationWhen FI individuals are allowed to self-fertilize, the P andp alleles segregate randomly during gamete formation.Their subsequent union at fertilization to form ¥2 individu- (a)als is also random, not being influenced by which alterna-tive alleles the individual gametes carry. What will the p2individuals look like? The possibilities may be visualized ina simple diagram called a Punnett square, named after itsoriginator, the English geneticist Reginald Crundall Pun-nett (figure 13.14). Mendels model, analyzed in terms of aPunnett square, clearly predicts that the F2 generationshould consist of % purple-flowered plants and 14 white-flowered plants, a phenotypic ratio of 3:1.The Laws of Probability CanPredict Mendels Results (b)A different way to express Mendels result is to say that FIGURE 13.14there are three chances in four (%) that any particular ¥2 in- A Punnett square, (a) To make a Punnett square, place thedividual will exhibit the dominant trait, and one chance in different possible types of female gametes along one side of afour (14) that an F2 individual will express the recessive trait. square and the different possible types of male gametes along theStating the results in terms of probabilities allows simple other, (b) Each potential zygote can then be represented as thepredictions to be made about the outcomes of crosses. If intersection of a vertical line and a horizontal line.both FI parents are Pp (heterozygotes), the probability thata particular F2 individual will be pp (homozygous recessive)is the probability of receiving a p gamete from the male (A) Mendels First Law of Heredity: Segregationtimes the probability of receiving a p gamete from the fe-male (A), or 1A. This is the same operation we perform in Mendels model thus accounts in a neat and satisfying way forthe Punnett square illustrated in figure 13.14. The ways the segregation ratios he observed. Its central assumption—probability theory can be used to analyze Mendels results that alternative alleles of a trait segregate from each other inis discussed in detail on page 272. heterozygous individuals and remain distinct—has since been verified in many other organisms. It is commonly re- ferred to as Mendels First Law of Heredity, or the LawFurther Generations of Segregation. As you saw in chapter 12, the segregationalAs you can see in figure 13.13, there are really three kinds behavior of alternative alleles has a simple physical basis, theof F2 individuals: 14 are pure-breeding, white-flowered indi- alignment of chromosomes at random on the metaphaseviduals (pp); Уг are heterozygous, purple-flowered individu- plate. It is a tribute to the intellect of Mendels analysis thatals (Pp); and 14 are pure-breeding, purple-flowered individ- he arrived at the correct scheme with no knowledge of theuals (PP). The 3:1 phenotypic ratio is really a disguised cellular mechanisms of inheritance; neither chromosomes1:2:1 genotypic ratio. nor meiosis had yet been described.250 Part IV Reproduction and Heredity
  11. 11. The Testcross To perform his testcross, Mendel crossed heterozygous FI individuals back to the parent homozygous for the reces- To test his model further, Mendel devised a simple and sive trait. He predicted that the dominant and recessive powerful procedure called the testcross. Consider a purple- traits would appear in a 1:1 ratio, and that is what he ob- flowered plant. It is impossible to tell whether such a plant served. is homozygous or heterozygous simply by looking at its For each pair of alleles he investigated, Mendel observed phenotype. To learn its genotype, you must cross it with phenotypic ¥2 ratios of 3:1 (see figure 13.13) and testcross some other plant. What kind of cross would provide the ratios very close to 1:1, just as his model predicted. answer? If you cross it with a homozygous dominant indi- Testcrosses can also be used to determine the genotype of vidual, all of the progeny will show the dominant pheno- an individual when two genes are involved. Mendel carried out type whether the test plant is homozygous or heterozygous. many two-gene crosses, some of which we will soon discuss. It is also difficult (but not impossible) to distinguish be- He often used testcrosses to verify the genotypes of particular tween the two possible test plant genotypes by crossing dominant-appearing p2 individuals. Thus an ¥2 individual with a heterozygous individual. However, if you cross the showing both dominant traits (A_ BJ) might have any of the test plant with a homozygous recessive individual, the two following genotypes: AABB, AaBB, AABb or AaBb. By crossing possible test plant genotypes will give totally different re- dominant-appearing ¥2 individuals with homozygous recessive sults (figure 13.15): individuals (that is, A_ B_ x aabb), Mendel was able to deter- mine if either or both of the traits bred true among the prog- Alternative 1: unknown individual homozygous (PP). eny, and so to determine the genotype of the ¥2 parent: PP x pp: all offspring have purple AABB trait A breeds true trait В breeds true flowers (Pp) AaBB trait В breeds true Alternative 2: unknown individual heterozygous (Pp). Pp x pp: Уг of offspring have white flow- AAbb trait A breeds true ers (pp) and И have purple flowers (Pp) AaBb т Dominant phenotype (unknown genotype) if Pp 00 Pp PPPP PP Pp PP Homozygous Homozygous recessive recessive (white) All offspring are purple; (white) Half of offspring are white; therefore, unknown therefore, unknown flower flower is homozygous is heterozygous Alternative 1 Alternative 2FIGURE 13.15A testcross. To determine whether an individual exhibiting a dominant phenotype, such as purple flowers, is homozygous orheterozygous for the dominant allele, Mendel crossed the individual in question with a plant that he knew to be homozygous recessive, inthis case a plant with white flowers. Chapter 13 Patterns of Inheritance 251
  12. 12. Mendels Second Law of Heredity:Independent AssortmentAfter Mendel had demonstrated that different alleles of agiven gene segregate independently of each other in Round yellow Wrinkled green seeds (RRYY) seeds (rryy)crosses, he asked whether different genes also segregate in-dependently. Mendel set out to answer this question in astraightforward way. He first established a series of pure-breeding lines of peas that differed in just two of the seven All round yellowpairs of characteristics he had studied. He then crossed seeds (RrYy)contrasting pairs of the pure-breeding lines to create het-erozygotes. In a cross involving different seed shape alleles(round, R, and wrinkled, r) and different seed color alleles Sperm(yellow, Y, and green, y), all the Fj individuals were identi-cal, each one heterozygous for both seed shape (Rr) and (RY к rY ryseed color (Yy). The FI individuals of such a cross are dihy- F2 generationbrids, individuals heterozygous for each of two genes. RRYY J RRYy RrYY RrYy The third step in Mendels analysis was to allow the di- 9/16 are round yellowhybrids to self-fertilize. If the alleles affecting seed shape 3/16 are round greenand seed color were segregating independently, then the RRYy RRyy RrYy ^вг Rryy 3/16 are wrinkled yellowprobability that a particular pair of seed shape alleles Eggs 1/16 are wrinkled greenwould occur together with a particular pair of seed coloralleles would be simply the product of the individual prob- RrYY RrYy rrYY rrYyabilities that each pair would occur separately. Thus, theprobability that an individual with wrinkled green seeds RrYy Rryy rrYy rryy(rryy) would appear in the ¥2 generation would be equal tothe probability of observing an individual with wrinkled FIGURE 13.16seeds (/4) times the probability of observing one with green Analyzing a dihybrid cross. This Punnett square analyzes theseeds (K), or УК,. results of Mendels dihybrid cross between plants with round Since the genes concerned with seed shape and those yellow seeds and plants with wrinkled green seeds. The ratio ofconcerned with seed color are each represented by a pair the four possible combinations of phenotypes is predicted to beof alternative alleles in the dihybrid individuals, four types 9:3:3:1, the ratio that Mendel found.of gametes are expected: RY, Ry, rY, and ry. Therefore, inthe F2 generation there are 16 possible combinations ofalleles, each of them equally probable (figure 13.16). Of These results are very close to a 9:3:3:1 ratio (whichthese, 9 possess at least one dominant allele for each gene would be 313:104:104:35). Consequently, the two genes ap-(signified R Y , where the dash indicates the presence peared to assort completely independently of each other.of either allele) and, thus, should have round, yellow Note that this independent assortment of different genes inseeds. Of the rest, 3 possess at least one dominant R allele no way alters the independent segregation of individual pairsbut are homozygous recessive for color (R_yy); 3 others of alleles. Round versus wrinkled seeds occur in a ratio of ap-possess at least one dominant Y allele but are homozygous proximately 3:1 (423:133); so do yellow versus green seedsrecessive for shape (rrY ); and 1 combination among the (416:140). Mendel obtained similar results for other pairs. 16 is homozygous recessive for both genes (rryy). The hy- Mendels discovery is often referred to as Mendelspothesis that color and shape genes assort independently Second Law of Heredity, or the Law of Independentthus predicts that the p2 generation of this dihybrid cross Assortment. Genes that assort independently of one an-will display a 9:3:3:1 ratio: nine individuals with round, other, like the seven genes Mendel studied, usually do soyellow seeds, three with round, green seeds, three with because they are located on different chromosomes, whichwrinkled, yellow seeds, and one with wrinkled, green segregate independently during the meiotic process of ga-seeds (see figure 13.16). mete formation. A modern restatement of Mendels Second What did Mendel actually observe? From a total of 556 Law would be that genes that are located on different chromo-seeds from dihybrid plants he had allowed to self-fertilize, somes assort independently during meiosis.he observed: Mendel summed up his discoveries about heredity in 315 round yellow (R_Y_) two laws. Mendels First Law of Heredity states that 108 round green (R yy) alternative alleles of a trait segregate independently; his 101 wrinkled yellow (rrY, ) Second Law of Heredity states that genes located on different chromosomes assort independently. 32 wrinkled green (rryy)252 Part IV Reproduction and Heredity
  13. 13. Mendelian Inheritance Is Not White Always Easy to AnalyzeMendels original paper describing his experiments, pub-lished in 1866, is charming and interesting to read. His ex-planations are clear, and the logic of his arguments is pre-sented lucidly. Although Mendels results did not receivemuch notice during his lifetime, three different investiga-tors independently rediscovered his pioneering paper in1900, 16 years after his death. They came across it whilesearching the literature in preparation for publishing their AAbb ааВВown findings, which closely resembled those Mendel hadpresented more than three decades earlier.Modified Mendelian Ratios In the decades following the rediscovery of Mendel in 1900, many investigators set out to test Mendels ideas. Ini- Purpletial work was carried out primarily in agricultural animalsand plants, since techniques for breeding these organismswere well established. However, scientists attempting toconfirm Mendels theory often had trouble obtaining thesame simple ratios he had reported. This was particularly AII/AaBbtrue for dihybrid crosses. Recall that when individuals het-erozygous for two different genes mate (a dihybrid cross), FIGURE 13.17 How epistasis affects grain color. The purple pigment foundfour different phenotypes are possible among the progeny: in some varieties of corn is the product of a two-stepoffspring may display the dominant phenotype for both biochemical pathway. Unless both enzymes are active (the plantgenes, either one of the genes, or for neither gene. Some- has a dominant allele for each of the two genes, A and B), notimes, however, it is not possible for an investigator to pigment is expressed.identify successfully each of the four phenotypic classes, be-cause two or more of the classes look alike. Such situationsproved confusing to investigators following Mendel. Why Was Emersons Ratio Modified? When genes act sequentially, as in a biochemical pathway, an allele ex-Epistasis pressed as a defective enzyme early in the pathway blocks the flow of material through the rest of the pathway. ThisOne example of such difficulty in identification is seen in makes it impossible to judge whether the later steps of thethe analysis of particular varieties of corn, Zevz mays. Some pathway are functioning properly. Such gene interaction,commercial varieties exhibit a purple pigment called antho- where one gene can interfere with the expression of an-cyanin in their seed coats, while others do not. In 1918, other gene, is the basis of the phenomenon called epistasis.geneticist R. A. Emerson crossed two pure-breeding corn The pigment anthocyanin is the product of a two-stepvarieties, neither exhibiting anthocyanin pigment. Surpris- biochemical pathway:ingly, all of the FI plants produced purple seeds. When two of these pigment-producing FI plants were Enzyme 1 Enzyme 2crossed to produce an ¥2 generation, 56% were pigment Starting molecule —> Intermediate —> Anthocyanin (Colorless) (Colorless) (Purple)producers and 44% were not. What was happening? Emer-son correctly deduced that two genes were involved in pro- To produce pigment, a plant must possess at least oneducing pigment, and that the second cross had thus been a good copy of each enzyme gene (figure 13.17). The domi-dihybrid cross like those performed by Mendel. Mendel nant alleles encode functional enzymes, but the recessive al-had predicted 16 equally possible ways gametes could com- leles encode nonfunctional enzymes. Of the 16 genotypesbine with each other, resulting in genotypes with a pheno- predicted by random assortment, 9 contain at least onetypic ratio of 9:3:3:1 (9 + 3 + 3 + 1 = 16). How many of dominant allele of both genes; they produce purple prog-these were in each of the two types Emerson obtained? He eny. The remaining 7 genotypes lack dominant alleles at ei-multiplied the fraction that were pigment producers (0.56) ther or both loci (3 + 3 + 1 = 7) and so are phenotypicallyby 16 to obtain 9, and multiplied the fraction that were not the same (nonpigmented), giving the phenotypic ratio of 9:7(0.44) by 16 to obtain 7. Thus, Emerson had a modified that Emerson observed. The inability to score enzymeratio of 9:7 instead of the usual 9:3:3:1 ratio. 2 when enzyme 1 is nonfunctional is an example of epistasis. Chapter 13 Patterns of Inheritance 253
  14. 14. Continuous VariationFew phenotypes are the result of the actionof only one gene. Instead, most traits reflectthe action of polygenes, many genes thatact sequentially or jointly. When multiplegenes act jointly to influence a trait such asheight or weight, the trait often shows arange of small differences. Because all of thegenes that play a role in determining pheno-types such as height or weight segregate in-dependently of one another, one sees a gra-dation in the degree of difference whenmany individuals are examined (figure13.18). We call this graduation continuous 30-variation. The greater the number of genesthat influence a trait, the more continuousthe expected distribution of the versions of ш яthat trait. .1 20 ~ 1 How can one describe the variation in a Т! С /trait such as the height of the individuals in Number оfigure 13.18я? Individuals range from quite j оshort to very tall, with average heights 1more common than either extreme. Whatone often does is to group the variation intocategories—in this case, by measuring the 1 1- эheights of the individuals in inches, round- 5 0" 5 У 6 О1ing fractions of an inch to the nearest whole Heightnumber. Each height, in inches, is a sepa- •rate phenotypic category. Plotting the (Ь)numbers in each height category produces a FIGURE 13.18histogram, such as that in figure 13.18£. Height is a continuously varying trait, (a) This photograph shows the variation inThe histogram approximates an idealized height among students of the 1914 class of the Connecticut Agricultural College.bell-shaped curve, and the variation can be Because many genes contribute to height and tend to segregate independently of onecharacterized by the mean and spread of another, there are many possible combinations of those genes, (b) The cumulativethat curve. contribution of different combinations of alleles to height forms a continuous spectrum of possible heights—a random distribution, in which the extremes are much rarer than the intermediate values.Pleiotropic EffectsOften, an individual allele will have morethan one effect on the phenotype. Such anallele is said to be pleiotropic. When the pioneering Pleiotropic effects are characteristic of many inheritedFrench geneticist Lucien Cuenot studied yellow fur in disorders, such as cystic fibrosis and sickle cell anemia,mice, a dominant trait, he was unable to obtain a true- both discussed later in this chapter. In these disorders,breeding yellow strain by crossing individual yellow mice multiple symptoms can be traced back to a single genewith each other. Individuals homozygous for the yellow al- defect. In cystic fibrosis, patients exhibit clogged bloodlele died, because the yellow allele was pleiotropic: one ef- vessels, overly sticky mucus, salty sweat, liver and pancreasfect was yellow color, but another was a lethal develop- failure, and a battery of other symptoms. All are pleio-mental defect. A pleiotropic gene alteration may be tropic effects of a single defect, a mutation in a gene thatdominant with respect to one phenotypic consequence encodes a chloride ion transmembrane channel. In sickle(yellow fur) and recessive with respect to another (lethal cell anemia, a defect in the oxygen-carrying hemoglobindevelopmental defect). In pleiotropy, one gene affects molecule causes anemia, heart failure, increased suscepti-many traits, in marked contrast to polygeny, where many bility to pneumonia, kidney failure, enlargement of thegenes affect one trait. Pleiotropic effects are difficult to spleen, and many other symptoms. It is usually difficult topredict, because the genes that affect a trait often perform deduce the nature of the primary defect from the range ofother functions we may know nothing about. its pleiotropic effects.254 Part IV Reproduction and Heredity
  15. 15. Lack of Complete Dominance Sperm Not all alternative alleles are fully dominant or fully recessive in het- erozygotes. Some pairs of alleles in- stead produce a heterozygous pheno- type that is either intermediate between those of the parents (incom- CRCR plete dominance), or representative of both parental phenotypes (codomi- nance). For example, in the cross of •Eggs red and white flowering Japanese four oclocks described in figure 13.19, allthe FI offspring had pink flowers— T generationindicating that neither red nor whiteflower color was dominant. Does this All CRCW CRCVexample of incomplete dominance CWCWargue that Mendel was wrong? Not at F2 generationall. When two of the FI pink flowers 1:2:1were crossed, they produced red-, CRCR:CRCW:CWCWpink-, and white-flowered plants in a1:2:1 ratio. Heterozygotes are simply FIGURE 13.19intermediate in color. Incomplete dominance. In a cross between a red-flowered Japanese four oclock, genotype CRCR, and a white-flowered one (CWCW), neither allele is dominant. The heterozygous progeny have pink flowers and the genotype CRCW. If two of theseEnvironmental Effects heterozygotes are crossed, the phenotypes of their progeny occur in a ratio of 1:2:1 (red:pink:white). The degree to which an allele is expressed may depend on the envi- ronment. Some alleles are heat- sensitive, for example. Traits influ- enced by such alleles are more sensi- tive to temperature or light than are the products of other alleles. The arctic foxes in figure 13.20, for ex- ample, make fur pigment only when the weather is warm. Similarly, thech allele in Himalayan rabbits and Siamese cats encodes a heat-sensitiveversion of tyrosinase, one of the en- FIGURE 13.20zymes mediating the production of Environmental effects on an allele. An arctic fox in winter has a coat that is almost white,melanin, a dark pigment. The ch so it is difficult to see the fox against a snowy background. In summer, the same foxs furversion of the enzyme is inactivated darkens to a reddish brown, so that it resembles the color of the surrounding tundra. Heat-at temperatures above about 33°C. sensitive alleles control this color change.At the surface of the main body andhead, the temperature is above 33°Cand the tyrosinase enzyme is inactive, while it is more A variety of factors can disguise the Mendelianactive at body extremities such as the tips of the ears and segregation of alleles. Among them are genetail, where the temperature is below 33°C. The dark interactions that produce epistasis, the continuousmelanin pigment this enzyme produces causes the ears, variation that results when many genes contribute to asnout, feet, and tail of Himalayan rabbits and Siamese trait, incomplete dominance that producescats to be black. heterozygotes unlike either parent, and environmental influences on the expression of phenotypes. Chapter 13 Patterns of Inheritance 255
  16. 16. 13.2 . are on chromes . • .-.-. -Chromosomes: The Vehiclesof Mendelian InheritanceChromosomes are not the only kinds of structures that seg-regate regularly when eukaryotic cells divide. Centriolesalso divide and segregate in a regular fashion, as do the mi-tochondria and chloroplasts (when present) in the cyto-plasm. Therefore, in the early twentieth century it was byno means obvious that chromosomes were the vehicles ofhereditary information.The Chromosomal Theory of InheritanceA central role for chromosomes in heredity was first sug-gested in 1900 by the German geneticist Karl Correns, inone of the papers announcing the rediscovery of Mendelswork. Soon after, observations that similar chromosomes FIGURE 13.21paired with one another during meiosis led directly to the Red-eyed (wild type) and white-eyed (mutant) Drosophila.chromosomal theory of inheritance, first formulated by The white-eyed defect is hereditary, the result of a mutation in athe American Walter Sutton in 1902. gene located on the X chromosome. By studying this mutation, Morgan first demonstrated that genes are on chromosomes. Several pieces of evidence supported Suttons theory. Onewas that reproduction involves the initial union of only twocells, egg and sperm. If Mendels model were correct, thenthese two gametes must make equal hereditary contribu-tions. Sperm, however, contain little cytoplasm, suggesting resolved. A single small fly provided the proof. In 1910that the hereditary material must reside within the nuclei of Thomas Hunt Morgan, studying the fruit fly Drosophilathe gametes. Furthermore, while diploid individuals have melanogaster, detected a mutant male fly, one that differedtwo copies of each pair of homologous chromosomes, ga- strikingly from normal flies of the same species: its eyesmetes have only one. This observation was consistent with were white instead of red (figure 13.21).Mendels model, in which diploid individuals have two Morgan immediately set out to determine if this newcopies of each heritable gene and gametes have one. Finally, trait would be inherited in a Mendelian fashion. He firstchromosomes segregate during meiosis, and each pair of ho- crossed the mutant male to a normal female to see if red ormologues orients on the metaphase plate independently of white eyes were dominant. All of the FI progeny had redevery other pair. Segregation and independent assortment eyes, so Morgan concluded that red eye color was domi-were two characteristics of the genes in Mendels model. nant over white. Following the experimental procedure that Mendel had established long ago, Morgan then crossed the red-eyed flies from the FI generation with eachA Problem with the Chromosomal Theory other. Of the 4252 F2 progeny Morgan examined, 782However, investigators soon pointed out one problem with (18%) had white eyes. Although the ratio of red eyes tothis theory. If Mendelian traits are determined by genes lo- white eyes in the ¥2 progeny was greater than 3:1, the re-cated on the chromosomes, and if the independent assort- sults of the cross nevertheless provided clear evidence thatment of Mendelian traits reflects the independent assort- eye color segregates. However, there was something aboutment of chromosomes in meiosis, why does the number of the outcome that was strange and totally unpredicted bytraits that assort independently in a given kind of organism Mendels theory—all of the white-eyed p2 flies тоете males!often greatly exceed the number of chromosome pairs the How could this result be explained? Perhaps it was im-organism possesses? This seemed a fatal objection, and it possible for a white-eyed female fly to exist; such individu-led many early researchers to have serious reservations als might not be viable for some unknown reason. To testabout Suttons theory. this idea, Morgan testcrossed the female FI progeny with the original white-eyed male. He obtained both white-eyed and red-eyed males and females in a 1:1:1:1 ratio, just asMorgans White-Eyed Fly Mendelian theory predicted. Hence, a female could haveThe essential correctness of the chromosomal theory of white eyes. Why, then, were there no white-eyed femalesheredity was demonstrated long before this paradox was among the progeny of the original cross?256 PartlV Reproduction and Heredity
  17. 17. Y chromosome X chromosome with X chromosome with white-eye gene red-eye gene Parents X Male Female F1 generation X Male Female F2 generationFIGURE 13.22Morgans experiment demonstratingthe chromosomal basis of sex linkagein Drosophila. The white-eyed mutantmale fly was crossed with a normal female.The FI generation flies all exhibited redeyes, as expected for flies heterozygous fora recessive white-eye allele. In the ¥2generation, all of the white-eyed flieswere male.Sex Linkage chromosome is said to be sex-linked. Knowing the white- eye trait is recessive to the red-eye trait, we can now seeThe solution to this puzzle involved sex. In Drosophila, the that Morgans result was a natural consequence of thesex of an individual is determined by the number of copies Mendelian assortment of chromosomes (figure 13.22).of a particular chromosome, the X chromosome, that an Morgans experiment was one of the most important inindividual possesses. A fly with two X chromosomes is a fe- the history of genetics because it presented the first clearmale, and a fly with only one X chromosome is a male. In evidence that the genes determining Mendelian traits domales, the single X chromosome pairs in meiosis with a indeed reside on the chromosomes, as Sutton had pro-large, dissimilar partner called the Y chromosome. The posed. The segregation of the white-eye trait has a one-to-female thus produces only X gametes, while the male pro- one correspondence with the segregation of the X chromo-duces both X and Y gametes. When fertilization involves some. In other words, Mendelian traits such as eye color inan X sperm, the result is an XX zygote, which develops into Drosophila assort independently because chromosomes do.a female; when fertilization involves a Y sperm, the result is When Mendel observed the segregation of alternative traitsan XY zygote, which develops into a male. in pea plants, he was observing a reflection of the meiotic The solution to Morgans puzzle is that the gene causing segregation of chromosomes.the white-eye trait in Drosophila resides only on the Xchromosome—it is absent from the Y chromosome. (We Mendelian traits assort independently because they arenow know that the Y chromosome in flies carries almost no determined by genes located on chromosomes thatfunctional genes.) A trait determined by a gene on the sex assort independently in meiosis. Chapter 13 Patterns of Inheritance 257
  18. 18. Genetic Recombination The chromosomal exchanges Stern demonstrated pro- vide the solution to the paradox, because crossing overMorgans experiments led to the general acceptance of can occur between homologues anywhere along theSuttons chromosomal theory of inheritance. Scientists length of the chromosome, in locations that seem to bethen attempted to resolve the paradox that there are more randomly determined. Thus, if two different genes areindependently assorting Mendelian genes than chromo- located relatively far apart on a chromosome, crossingsomes. In 1903 the Dutch geneticist Hugo de Vries sug- over is more likely to occur somewhere between themgested that this paradox could be resolved only by assum- than if they are located close together. Two genes can being that homologous chromosomes exchange elements on the same chromosome and still show independent as-during meiosis. In 1909, French cytologist F. A. Janssens sortment if they are located so far apart on the chromo-provided evidence to support this suggestion. Investigating some that crossing over occurs regularly between themchiasmata produced during amphibian meiosis, Janssens (figure 13.24).noticed that of the four chromatidsinvolved in each chiasma, twocrossed each other and two did not.He suggested that this crossing of Abnormality at F! femalechromatids reflected a switch in one locus ofchromosomal arms between the pa- Abnormality at /F] X chromosometernal and maternal homologues, in- another locus of U X chromosomevolving one chromatid in each ho-mologue. His suggestion was notaccepted widely, primarily because car •~> "*•it was difficult to see how two chro- No в ~ f -s • crossing oumatids could break and rejoin at ex- overactly the same position.Crossing OverLater experiments clearly estab- car 1 4 " 4. car T + r ~ 8 + <~*lished that Janssens was indeed cor- J LJrect. One of these experiments, • car Q Qperformed in 1931 by American ge- + i 4~- ~-~neticist Curt Stern, is described in --X.figure 13.23. Stern studied two sex- Fertilization X / / .."-^^linked eye traits in Drosophila strains by spermwhose X chromosomes were visibly from carnation / 1V F-| male ч 8abnormal at both ends. He first ex- r-*. car p / ^ ^ ^I car ^ ^ car car )+amined many flies and identified ^car car 4- -IB + 4- 4- ^ вthose in which an exchange had oc-curred with respect to the two eyetraits. He then studied the chromo- v> ] ^ D Carnation, Normal Carnationsomes of those flies to see if their bar BarX chromosomes had exchangedarms. Stern found that all of the in-dividuals that had exchanged eye Parental combinations of Recombinant combinations both genetic traits and of both genetic traits andtraits also possessed chromosomes chromosome abnormalities chromosome abnormalitiesthat had exchanged abnormal ends.The conclusion was inescapable: FIGURE 13.23genetic exchanges of traits such as Sterns experiment demonstrating the physical exchange of chromosomal arms duringeye color involve the physical ex- crossing over. Stern monitored crossing over between two genes, the recessive carnation eyechange of chromosome arms, a phe- color (car) and the dominant bar-shaped eye (B), on chromosomes with physical peculiaritiesnomenon called crossing over. visible under a microscope. Whenever these genes recombined through crossing over, theCrossing over creates new combina- chromosomes recombined as well. Therefore, the recombination of genes reflects a physicaltions of genes, and is thus a form of exchange of chromosome arms. The "+" notation on the chromosomes refers to the wild-typegenetic recombination. allele, the most common allele for a particular gene.258 Part IV Reproduction and Heredity
  19. 19. Using Recombination to Make Genetic Maps Chromosome Location of genes number Because crossing over is more frequent between two genes that are relatively far apart than between two that are close together, the frequency of crossing over can be used to map © the relative positions of genes on chromosomes. In a cross, the proportion of progeny exhibiting an exchange between Flower color Seed color two genes is a measure of the frequency of crossover events between them, and thus indicates the relative distance sepa- rating them. The results of such crosses can be used to con- struct a genetic map that measures distance between genesin terms of the frequency of recombination. One "mapunit" is defined as the distance within which a crossover event is expected to occur in an average of 1% of gametes.A map unit is now called a centimorgan, after ThomasHunt Morgan. In recent times new technologies have allowed geneti-cists to create gene maps based on the relative positionsof specific gene sequences called restriction sequences be-cause they are recognized by DNA-cleaving enzymes Flower position Pod shape Plantcalled restriction endonucleases. Restriction maps, dis- heightcussed in chapter 18, have largely supplanted genetic re-combination maps for detailed gene analysis because they ©are far easier to produce. Recombination maps remain Pod colorthe method of choice for genes widely separated on achromosome.The Three-Point Cross. In constructing a genetic map,one simultaneously monitors recombination among threeor more genes located on the same chromosome, referredto as syntenic genes. When genes are close enough to-gether on a chromosome that they do not assort indepen- ©dently, they are said to be linked to one another. A cross Seed shapeinvolving three linked genes is called a three-point cross.Data obtained by Morgan on traits encoded by genes on FIGURE 13.24the X chromosome of Drosophila were used by his student The chromosomal locations of the seven genes studied byA. H. Sturtevant, to draw the first genetic map (figure Mendel in the garden pea. The genes for plant height and pod13.25). By convention, the most common allele of a gene is shape are very close to each other and rarely recombine. Plantoften denoted on a map with the symbol "+" and is desig- height and pod shape were not among the pairs of traits Mendelnated as wild type. All other alleles are assigned specific examined in dihybrid crosses. One wonders what he would havesymbols. made of the linkage he surely would have detected had he tested this pair of traits.FIGURE 13.25The first genetic map. This map ofthe X chromosome of Drosophila was Geneticprepared in 1913 by A. H. Sturtevant, a Recombination mapstudent of Morgan. On it he located the Five frequencies .58 r~ - rrelative positions of five recessive traits traits у andw 0.010that exhibited sex linkage by estimating у Yellow body color v andm 0.030their relative recombination frequencies v andr 0.269 w White eye color ол тin genetic crosses. Sturtevant arbitrarily v and w 0.300 -Ot v Vermilion eye color .31 уchose the position of the yellow gene т Miniature wing v and/ 0.322as zero on his map to provide a frame r Rudimentary wing w and т 0.327of reference. The higher the у andm 0.355 .01 — wrecombination frequency, the farther wandr 0.450 0 Г-. Уapart the two genes. с Chapter 13 Patterns of Inheritance 259