atterns inheritance

Brooker−Widmaier−Graham−Stiling: Biology

III. Nucleic Acid Structure and DNA Replication

17. Complex Patterns of Inheritance

96 © The McGraw−Hill Companies, 2008

COMPLEX PATTERNSOF INHERITANCEC H A P T E R O U T L I N E

17.1 Gene Interactions

17.2 Genes on the Same Chromosome: Linkage,Recombination, and Mapping

17.3 Extranuclear Inheritance: Organelle Genomes

17.4 X Inactivation, Genomic Imprinting,and Maternal Effect

In Chapter 16, we examined inheritance patterns in whichthe outcome of a single trait was governed by a single gene.In the cases we considered, the alleles segregated and

assorted independently, allowing us to predict the phenotypesof offspring from the genotypes of their parents. These pheno-types occurred in definite ratios and they did not overlap—apea plant was either tall or dwarf; a blood type was either A, B,or O. The inheritance patterns of most traits are more complex,however, and in this chapter we will examine some of the fac-tors that complicate the prediction of phenotypes.

In the first section of the chapter, we will consider how twoor more different genes may affect the outcome of a single trait.For example, we examine continuously varying traits like humanskin color, and you will see how the interaction of multiplegenes and environmental influences can produce such a contin-uum. In the rest of the chapter we will consider inheritance pat-terns that defy Mendel’s laws of inheritance. First we discussgenes that are linked on the same chromosome and therefore donot assort independently. Next we consider the genes found inchloroplasts and mitochondria, which defy the law of segrega-tion. Don’t worry, Mendel’s laws do describe most inheritancepatterns, and they accurately reflect the behavior of chromo-somes during meiosis. However, as you will learn in this chap-ter, they simply don’t apply to all of the genes that eukaryoticorganisms possess. We will end the chapter with a discussion ofthree inheritance patterns, X inactivation, genomic imprinting,and maternal effect, that were not easily explained until re-searchers began to unravel genetic events that occur at the cel-lular and molecular levels. As you will learn, males and femalesdon’t always regulate their genes in the same way, and this canlead to seemingly bizarre patterns of inheritance that are dis-tinct from X-linked and sex-influenced inheritance patterns,

which we considered in the previous chapter. An exciting ad-vance over the past few decades has been a better understand-ing of such unusual patterns of inheritance.

Studies of complex inheritance patterns such as those de-scribed in this chapter have helped us appreciate more fully howgenes influence phenotypes. These studies have revealed an as-tounding variety in the ways that inheritance occurs. The picturethat emerges is of a wonderful web of diverse mechanisms bywhich genes give rise to phenotypes. Table 17.1 provides a sum-mary of the most common patterns of inheritance.

17.1 Gene InteractionsThe study of single genes was pivotal in establishing the sci-ence of genetics. This focus allowed Mendel to formulate thebasic laws of inheritance for traits with a simple dominant/recessive inheritance pattern. Likewise, this approach helpedlater researchers understand inheritance patterns involving in-complete dominance and codominance, as well as traits that areinfluenced by an individual’s sex. In reality, however, all ornearly all traits are influenced by many genes. For example, inboth plants and animals, height is affected by genes that encodeproteins involved in the production of growth hormones, celldivision, the uptake of nutrients, metabolism, and many otherfunctions. A defect in any of these genes is likely to have a neg-ative impact on an individual’s height.

If height is controlled by many genes, you may be wonder-ing how Mendel was able to study the effects of a single genethat produced tall or dwarf pea plants. The answer lies in thegenotypes of his strains. Although many genes affect the heightof pea plants, Mendel chose true-breeding strains that differed

Snail shells (Lymnaea peregra) that coil to the right or left. The directionof coiling of a snail’s shell is an example of a complex inheritance pattern.




97© The McGraw−Hill Companies, 2008

with regard to only one of these genes. As a hypothetical exam-ple, let’s suppose that pea plants have 10 genes affecting height,which we will call K, L, M, N, O, P, Q, R, S, and T. The geno-types of two hypothetical strains of pea plants may be:

Tall strain: KK LL MM NN OO PP QQ RR SS TT

Dwarf strain: KK LL MM NN OO PP QQ RR SS tt

In this example, the tall and dwarf strains differ at only asingle locus. One strain is TT and the other is tt, and this ac-counts for the difference in their height. If we make crosses oftall and dwarf plants, the genotypes of the F2 offspring will dif-fer with regard to only one gene; the other nine genes will beidentical in all of them. This approach allows a researcher tostudy the effects of a single gene even though many genes mayaffect a single trait.

In this section, we will examine situations in which a singletrait is controlled by two or more genes, each of which has two

or more alleles. This phenomenon is called a gene interaction.As you will see, allelic variation at two or more loci may affectthe outcome of traits in different ways. First we will look atinteractions in which an allele of one gene prevents the expres-sion of an allele of a different gene. Then we will discuss inter-actions in which multiple genes have additive effects on a singletrait. These additive effects, together with environmental influ-ences, account for the continuous phenotypic variation that wesee for most traits.

An Epistatic Gene Interaction Occurs Whenthe Allele of One Gene Masks the PhenotypicEffects of a Different Gene

In some gene interactions, the alleles of one gene mask the ex-pression of the alleles of another gene. This phenomenon iscalled epistasis (Greek ephistanai, stopping). An example is theunexpected gene interaction discovered by William Batesonand Reginald Punnett in the early 1900s, when they were study-ing crosses involving the sweet pea, Lathyrus odoratus. A crossbetween a true-breeding purple-flowered plant and a true-breeding white-flowered plant produced an F1 generation withall purple-flowered plants and an F2 generation with a 3:1 ratioof purple- to white-flowered plants. Of course, Mendel’s lawspredicted this result. The surprise came when the researcherscrossed two different varieties of white-flowered sweet peas(Figure 17.1). All of the F1 generation plants had purple flow-ers! When these plants were allowed to self-fertilize, the F2

generation had purple-flowered and white-flowered plants ina 9:7 ratio. From these results, Bateson and Punnett deducedthat two different genes were involved. To have purple flow-ers, a plant must have one or two dominant alleles for each ofthese genes. The relationships among the alleles are as follows:

C (one allele for purple) is dominant to c (white)

P (an allele for purple of a different gene) is dominantto p (white)

cc masks P, or pp masks C, in either case producingwhite flowers

A plant that was homozygous for either c or p would havewhite flowers even if it had a purple-producing allele at theother locus.

Epistatic interactions often arise because two or more dif-ferent proteins are involved in a single cellular function. Forexample, two or more proteins may be part of an enzymaticpathway leading to the formation of a single product. This isthe case for the formation of a purple pigment in the sweet peastrains we have been discussing:

Enzyme C Enzyme PColorless Colorless Purpleprecursor intermediate pigment

In this example, a colorless precursor molecule must beacted on by two different enzymes to produce the purple pig-

350 UNIT III – CHAPTER 17

Table 17.1 Different Types of Inheritance Patterns

Type Description

Mendelian Inheritance patterns in which a single gene affectsa single trait, and the alleles segregate and assortindependently. These patterns include simpledominant/recessive traits, X-linked traits controlledby a single gene, incomplete dominance, codomi-nance, and sex-influenced traits (refer back toTable 16.1).

Epistasis A type of gene interaction in which the alleles ofone gene mask the effects of a dominant allele ofanother gene.

Continuous Inheritance pattern in which the offspring displayvariation a continuous range of phenotypes. This pattern is

produced by the additive interactions of severalgenes, together with environmental influences.

Linkage Inheritance patterns involving two or more genesthat are close together on the same chromosome.These genes do not assort independently.

Extranuclear Transmission pattern of genes found in the DNAinheritance of mitochondria or chloroplasts, which are

inherited independently of genes in the nucleusand do not segregate during meiosis. Usuallythese genes are inherited from the mother.

X inactivation Phenomenon of female mammals in which oneX chromosome is inactivated in every somatic cell,producing a mosaic phenotype. Most genes on theinactivated X chromosome are not expressed.

Genomic Inheritance pattern in which an allele from oneimprinting parent is inactivated in the somatic cells of the

offspring, while the allele from the other parent isexpressed.

Maternal effect Inheritance pattern in which the genotype of themother determines the phenotype of the offspring.This occurs because maternal effect genes of themother provide gene products to developing eggcells.





ment. Gene C encodes a functional protein, enzyme C, that con-verts the colorless precursor into a colorless intermediate. Therecessive c allele results in a lack of production of enzyme C inthe homozygote. Gene P encodes the functional enzyme P,which converts the colorless intermediate into the purple pig-ment. Like the c allele, the p allele results in an inability to pro-duce a functional protein. A plant that is homozygous for eitherof the recessive alleles will not make any functional enzyme C

or enzyme P. When either of these enzymes is missing, the plantcannot make the purple pigment and has white flowers.

Polygenic Inheritance and EnvironmentalInfluences Produce Continuous PhenotypicVariation

As we have just seen, an epistatic interaction causes the allelesof one gene to mask the effects of a different gene. Let’s nowturn to another way that the alleles of different genes may affectthe phenotype of a single trait. In many cases, the effects ofalleles may be additive. This has been observed for many traits,particularly those that are quantitative in nature.

Until now we have discussed the inheritance of traits withclearly defined phenotypic variants, such as red or white eyes infruit flies. These are known as discrete traits, or discontinuoustraits, because the phenotypes do not overlap. For most traits,however, the phenotypes cannot be sorted into discrete cate-gories. The majority of traits in all organisms are continuoustraits, also called quantitative traits, which show continuousvariation over a range of phenotypes. In humans, quantitativetraits include height, weight, skin color, metabolic rate, and heartsize, to mention a few. In the case of domestic animals and plantcrops, many of the traits that people consider desirable are quan-titative in nature, such as the number of eggs a chicken lays, theamount of milk a cow produces, and the number of apples onan apple tree. Consequently, much of our modern understand-ing of quantitative traits comes from agricultural research.

Quantitative traits are polygenic, which means that severalor many genes contribute to the outcome of the trait. For manypolygenic traits, genes contribute to the phenotype in an addi-tive way. Another important factor is the environment. As wesaw in Chapter 16, the environment plays a vital role in the phe-notypic expression of genes. Environmental factors often havea major impact on quantitative traits. For example, an animal’sdiet affects its weight, and the amount of rain and sunlight thatfall on an apple tree affect how many apples it produces.

Because quantitative traits are polygenic and greatly influ-enced by environmental conditions, the phenotypes among dif-ferent individuals may vary substantially in any given popula-tion. As an example, let’s consider skin pigmentation in people.This trait is influenced by several genes that tend to interact inan additive way. As a simplified example, let’s consider a popu-lation in which this trait is controlled by three genes, which wewill designate A, B, and C. Each gene has a dark allele, desig-nated AD, BD, or CD, and a light allele, designated AL, BL, or CL,respectively. All of the alleles encode enzymes that cause thesynthesis of skin pigment, but the enzymes encoded by darkalleles cause more pigment synthesis than the enzymes en-coded by light alleles. Figure 17.2 considers a hypothetical casein which people who were heterozygous for all three genes pro-duced a large population of offspring. The bar graph shows thegenotypes of the offspring, grouped according to the total num-ber of dark alleles. As shown by the shading of the figure, skinpigmentation increases as the number of dark alleles increases.

COMPLEX PATTERNS OF INHERITANCE 351

White variety #1 CCpp

White variety #2 ccPP

CP Cp cP cp

CP

Cp

cP

cp

CCPPPurple

CCPpPurple

CcPPPurple

CcPpPurple

F1

F2

P

CCPpPurple

CcPPPurple

CcPpPurple

CcppWhite

ccPpWhite

ccppWhite

ccPpWhite

ccPPWhite

CcPpPurple

CCppWhite

CcppWhite

CcPpPurple

All purple CcPp

Self-fertilization

�

Figure 17.1 Epistasis in the sweet pea. The color ofthe sweet pea flower is controlled by two genes, each with adominant and a recessive allele. Each of the dominant alleles(C and P) encodes an enzyme required for the synthesis of purplepigment. A plant that is homozygous recessive for either gene (ccor pp) cannot synthesize the pigment and will have white flowers.

Biological inquiry: In a Ccpp individual, which functional enzymeis missing? Is it the enzyme encoded by the C or P gene?





Offspring who have no dark alleles or no light alleles—that is,who are homozygous for all three genes—are fewer in numberthan those with some combination of dark and light alleles. Asseen in the bell-shaped curve above the bar graph, the pheno-types of the offspring fall along a continuum. This continuousphenotypic variation, which is typical of quantitative traits, isproduced by genotypic differences together with environmentaleffects. A second bell-shaped curve (the dashed line) depictsthe expected phenotypic range if the same population of off-spring had been raised in a sunnier environment, which in-creases pigment production. These two curves illustrate how theenvironment can also have a significant influence on the rangeof phenotypes.

In our discussion of genetics, we tend to focus on discretetraits because this makes it easier to relate a specific genotypewith a phenotype. This is usually not possible for continuoustraits. For example, as depicted in the middle bar of Figure 17.2,seven different genotypes can produce individuals with a me-dium amount of pigmentation. Nevertheless, it is important toemphasize that the majority of traits in all organisms are con-tinuous, not discrete. Most traits are influenced by multiplegenes, and the environment has an important impact on thephenotypic outcome.

17.2 Genes on the SameChromosome: Linkage,Recombination, and Mapping

In all of the inheritance patterns we have studied so far, thealleles segregate and assort independently as predicted by Men-del’s laws. As we have seen, phenotypes can be influenced by avariety of factors, including gene interactions and environmen-tal effects, that make it difficult to relate genotype to phenotype.Even so, if we understand all of these factors and take them intoaccount, we can see that each of the genes is transmitted accord-ing to Mendel’s laws.

In the rest of this chapter, we will consider inheritance pat-terns in which the outcome of a cross violates one of Mendel’slaws. In this section, we focus on transmission patterns that donot conform to the law of independent assortment. We will beginby examining the first experimental cross that demonstrated thispattern. You will learn that this pattern was explained by ThomasHunt Morgan, who proposed that genes located close to eachother on the same chromosome tend to be inherited as a group.Finally, we will see how crossing over between such genes pro-vided the first method of mapping genes on chromosomes.


ALALBLBLCLCL ADADBDBDCDCD

ADALBLBLCLCL

ALALBDBLCLCL

ALALBLBLCDC L

ALADBDBDC DC D

ADADBLBDC DC D

ADADB DBDCLC D

ADADBLBLCLCL

ALALBDBDCLCL

ALALBLBLC DC D

ADALBDBLCLCL

ADALBLBLCDCL

ALALBDBLC DCL

ADALBDBLCDCL

ADADBDBLCLCL

ADADBLBLCDCL

ADALBDBDCLCL

ADALBLBLCDCD

ALALBDBLCDCD

ALALBDBDCDCL

ADALBDBLCDCL � ADALBDBLCDCL

ALALBDBDCDCD

ADADBLBLCDCD

ADADBDBDCLC L

ALADBLBDC DC D

ALADBDBDCLCD

ADADBLBDCLCD

6Number oflight alleles

Number ofdark alleles

20/64

15/64

10/64

5/64

Fra

ctio

n of

peo

ple

with

sam

e ph

enot

ype

0

Light DarkPigmentation

5 4 3 2 1 0

0 1 2 3 4 5 6

Same population raised in a sunnier environment

Figure 17.2 Continuous variation in a polygenic trait. Skin color is a polygenic trait that can display a continuum of phenotypes.The bell curve on the left (solid line) shows the range of skin pigmentation in a hypothetical human population. The bar graphs belowthe curve show the additive effects of three genes that affect pigment production in this population; each bar shows the fraction ofpeople with a particular number of dark alleles (AD, BD, and CD ) and light alleles (AL, BL, and CL). The bell curve on the right (dashed line)represents the expected range of phenotypes if the same population was raised in a sunnier environment.





Bateson and Punnett’s Crosses of SweetPeas Showed That Genes Do Not AlwaysAssort Independently

In Chapter 16, we learned that the independent assortment of al-leles is due to the random alignment of homologous chromosomesduring meiosis (refer back to Figure 16.11). But what happenswhen the alleles of different genes are on the same chromo-some? A typical chromosome contains many hundreds or evena few thousand different genes. When two genes are close to-gether on the same chromosome, they tend to be transmitted as aunit, a phenomenon known as linkage. A group of genes that usu-

ally stay together during meiosis is called a linkage group, andthe genes in the group are said to be linked. In a two-factor cross,linked genes do not follow the law of independent assortment.

The first study showing linkage between two different geneswas a cross of sweet peas carried out by William Bateson andReginald Punnett in 1905. A surprising result occurred whenthey conducted a cross involving two different traits, flowercolor and pollen shape (Figure 17.3). One of the parent plantshad purple flowers (PP) and long pollen (LL); the other hadred flowers (pp) and round pollen (ll). As Bateson and Pun-nett expected, the F1 plants all had purple flowers and longpollen (PpLl). The unexpected result came in the F2 generation.


Observe the phenotypes of the F1 offspring.

Allow the F1 offspring to self-fertilize.

Observe the phenotypes of the F2 offspring.

Cross a plant with purple flowers and long pollen to a plant with red flowersand round pollen.

HYPOTHESIS The alleles of different genes assort independently of each other.

PPLL � ppll

Purple flowers,long pollen



Red flowers,round pollen

PpLl

PL and pl gametes — more frequent

Pl and pL gametes — less frequent

Meiosis

�

Fertilization

STARTING MATERIALS True-breeding sweet pea strains that differ with regard to flower color and pollen shape.

Experimental level Conceptual level

1

2

3

4

�

Purple flowers, long pollen

Purple flowers, long pollen

Purple flowers, round pollen

Red flowers, long pollen

Red flowers, round pollen

15.6 : 1.0 : 1.4 4.5:

F2 offspring having phenotypes of purple flowers, long pollen or red flowers, round pollen occurred more frequently than expected from Mendel’s law of independent assortment.

Figure 17.3 A cross of sweet peas showing that independent assortment does not always occur.





Although the offspring displayed the four phenotypes predictedby Mendel’s laws, the observed numbers of offspring did notconform to the predicted 9:3:3:1 ratio. Rather, as seen in the datain Figure 17.3, the F2 generation had a much higher proportionof the two phenotypes found in the parental generation: purpleflowers with long pollen, and red flowers with round pollen.

These results did not support the law of independent assortment.Bateson and Punnett suggested that the transmission of flowercolor and pollen shape was somehow coupled, so that these traitsdid not always assort independently. Although the law of inde-pendent assortment applies to many other genes, in this exam-ple, the hypothesis of independent assortment was rejected.


Linkage and Crossing Over Produce Parentaland Recombinant Phenotypes

Although Bateson and Punnett realized their results did notconform to Mendel’s law of independent assortment, they didnot provide a clear explanation for their data. A few years later,Thomas Hunt Morgan obtained similar ratios in crosses of fruitflies while studying the transmission pattern of genes locatedon the X chromosome. Like Bateson and Punnett, Morgan ob-served many more F2 offspring with the parental combinationof traits than would be predicted on the basis of independentassortment. To explain his data, Morgan proposed these ideas:

1. When different genes are located on the same chromosome,the traits that are determined by those genes are mostlikely to be inherited together.

2. Due to crossing over during meiosis, homologous chromo-somes can exchange pieces of chromosomes and createnew combinations of alleles (refer back to Figure 15.17).

3. The likelihood of crossing over depends on the distancebetween two genes. Crossovers between homologouschromosomes are much more likely to occur between twogenes that are farther apart in the chromosome comparedto two genes that are closer together.

To illustrate the first two of these ideas, Figure 17.4 consid-ers a series of crosses involving two genes that are linked on thesame chromosome in Drosophila. The P generation cross is be-tween flies that are homozygous for alleles that affect body colorand wing shape. The female is homozygous for the wild-typealleles that produce gray body color (b�b�) and straight wings(c�c�); the male is homozygous for mutant alleles that produceblack body color (bb) and curved wings (cc). Note that the sym-bols for the genes are based on the name of the mutant allele;the wild-type allele is indicated by a superscript plus sign (+).

The chromosomes next to the flies in Figure 17.4 show thearrangement of these alleles. If the two genes are on the samechromosome, we know the arrangement of alleles in the P gen-eration flies because these flies are homozygous for both genes(b�b�c�c� or bbcc). In the P generation female on the left, b� andc� are linked, while b and c are linked in the male on the right.

Let’s now look at the outcome of the crosses in Figure 17.4.As expected, the F1 offspring (b�bc�c) all had gray bodies andstraight wings, confirming that these are the dominant traits. Inthe next cross, F1 females were mated to males that were homo-zygous for both recessive alleles (bbcc). A cross in which anindividual with a dominant phenotype is mated with a homozy-gous recessive individual is called a testcross, as described inChapter 16. In the crosses we are discussing here, the purposeof the testcross is to determine whether the genes for body colorand wing shape are linked. If the genes were on different chro-mosomes and assorted independently, this testcross should haveproduced equal numbers of F2 offspring with the four possiblephenotypes. The observed numbers, shown above the F2 phe-notypes, clearly conflict with this prediction based on indepen-dent assortment. The two most abundant phenotypes are thosewith the combinations of characteristics in the P generation:gray bodies and straight wings or black bodies and curved wings.These offspring are called nonrecombinants because their com-bination of traits has not changed from the parental generation.They are also termed parental types. The smaller number ofoffspring that have a different combination of traits—gray bod-ies and curved wings or black bodies and straight wings—arerecombinants or nonparental types.

How do we explain the occurrence of recombinants whengenes are linked on the same chromosome? As shown beside theflies of the F2 generation in Figure 17.4, each recombinant indi-vidual has a chromosome that is the product of a crossover. Thecrossover occurred while the F1 female fly was making egg cells.

5

Phenotypes ofF2 offspring

Observednumber

Observedratio

Expectedratio

Expectednumber

Purple flowers, long pollenPurple flowers, round pollenRed flowers, long pollenRed flowers, round pollen

2961927 85

15.6 1.0 1.4 4.5

240 80 80 27

9 3 3 1

THE DATA





As shown below, four different egg cells are possible: Due to crossing over, two of the four egg cells produced bymeiosis have recombinant chromosomes. What happens wheneggs containing such chromosomes are fertilized in the test-cross? Each of the male fly’s sperm cells carries a chromosomewith the two recessive alleles. If the egg contains the recom-binant chromosome carrying the b� and c alleles, the testcrosswill produce an F2 offspring with a gray body and curvedwings. If the egg contains the recombinant chromosome carry-ing the b and c� alleles, F2 offspring will have a black bodyand straight wings. Therefore, crossing over in the F1 femalecan explain the occurrence of both types of F2 recombinantoffspring.


b�b�

c�c�

b�

c�

b

c

b

c�

b�

c

bb

cc

Crossover

Homologs in F1 female

Nonrecombinantchromosomes

Recombinantchromosomes

Meiosis

Homozygous dominantb�b�c�c�

b�bc�c bbcc b�bcc bbc�c

b�bc�c

Homozygous recessivebbcc

bbcc

Gray body, straight wings Black body, curved wings

Gray body, straight wings

Gray body, straight wings

Black body, curved wings

Gray body, curved wings

Black body, straight wings

Black body, curved wings

�

�

b� b�

c� c�

b� b

c� c

b b

c� c

b� b

c c

b b

c c

b b

c c

b b

c c

b�

c�

b

c

Testcross

P

F1

F2

Total

Nonrecombinants Recombinants

Number observed

Number expected based onindependent assortment

371

250

359

250

133

250

137

250

1,000

1,000

Figure 17.4 Linkage and recombination of alleles. An experimenter crossed b�b�c�c+ and bbcc flies to produce F1 heterozygotes.F1 females were then testcrossed to bbcc males. The large number of parental phenotypes in the F2 generation suggests that the twogenes are linked on the same chromosome. F2 recombinant phenotypes occur because the alleles can be rearranged by crossing over.





Morgan’s ideas about linkage and crossing over were basedon similar data, derived from his studies of genes on the X chro-mosome. The idea that linked genes tend to be inherited to-gether explained the high frequency of parental combinations oftraits in certain crosses. The suggestion that crossing over pro-duces chromosomes with new allele combinations accounted forthe occurrence of recombinant phenotypes. Morgan’s third idearegarding linkage was that the frequency of crossing over be-tween linked genes depends on the distance between them. Thissuggested a method for determining the relative positions ofgenes on a chromosome, as we will see next.

Recombination Frequencies Provide a Methodfor Mapping Genes Along Chromosomes

The oldest approach to studying the arrangement of genes in aspecies’ genome is called genetic linkage mapping (also knownas gene mapping or chromosome mapping). This experimentalmethod is used to determine the linear order of genes that arelinked to each other along the same chromosome. As depicted inFigure 17.5, this linear arrangement is shown in a chart knownas a genetic linkage map. Each gene has its own unique locusat a particular site within a chromosome. For example, the genefor black body color (b) that we discussed earlier is located nearthe middle of the chromosome, while the gene for curved wings(c) is closer to one end. The first genetic linkage map, showingfive genes on the Drosophila X chromosome, was constructed in1911 by Alfred Sturtevant, an undergraduate who spent time inMorgan’s laboratory.

Genetic linkage mapping allows us to estimate the relativedistances between linked genes based on the likelihood that acrossover will occur between them. This likelihood is propor-tional to the distance between the genes, as Morgan first pro-posed. If the genes are very close together, a crossover is unlikelyto begin in the region between them. However, if the genes arevery far apart, a crossover is more likely to be initiated betweenthem and thereby recombine their alleles. Therefore, in a crossinvolving two genes on the same chromosome, the percentage ofrecombinant offspring is correlated with the distance betweenthe genes. This correlation provides the experimental basis forgene mapping. If a two-factor testcross produces many recombi-nant offspring, the experimenter concludes that the genes are farapart. If very few recombinant offspring are observed, the genesmust be close together.

To find the distance between two genes, the experimentermust determine the frequency of crossing over between them,called their recombination frequency. This is accomplished byconducting a testcross. As an example, let’s refer back to theDrosophila testcross described in Figure 17.4. As we discussed,the genes for body color and wing shape are on the same chro-mosome; the recombinant offspring are the result of crossing

over during egg formation in the F1 female. We can use the datafrom the testcross shown in Figure 17.4 to estimate the distancebetween these two genes. The map distance between two linkedgenes is defined as the number of recombinant offspring dividedby the total number of offspring times 100.

Map distance �Number of recombinant offspring

Total number of offspring � 100

�133 � 137

371 � 359 � 133 � 137� 100

� 27.0 map units

The units of distance are called map units (mu), or some-times centiMorgans (cM) in honor of Thomas Hunt Morgan.One map unit is equivalent to a 1% recombination frequency.In this example, 270 out of 1,000 offspring are recombinants, sothe recombination frequency is 27% and the two genes are 27.0mu apart.

Genetic linkage mapping has been useful for analyzing thegenes of organisms that are easily crossed and produce manyoffspring in a short time. It has been used to map the genes ofseveral plant species and of certain species of animals, such as


Mutant phenotype Wild-type phenotype

Aristaless, al Long aristae

Dumpy wings, dp Long wings

Black body, b Gray body

Purple eyes, pr Red eyes

Vestigial wings, vg Long wings

Curved wings, c Straight wings

Brown eyes, bw Red eyes

0.0

13.0

48.5

54.5

67.0

75.5

104.5

Map units

Figure 17.5 A simplified genetic linkage map. This mapshows the relative locations of a few genes along a chromosomein Drosophila melanogaster. The name of each gene is basedon the mutant phenotype. The numbers on the left are map units(mu). The distance between two genes, in map units, correspondsto their recombination frequency in testcrosses.





Drosophila. However, for most organisms, including humans,linkage mapping is impractical due to long generation times orthe inability to carry out experimental crosses. Fortunately,many alternative methods of gene mapping have been devel-oped in the past few decades that are faster and do not dependon crosses. These newer cytological and molecular approaches,which we will discuss in Chapter 20, are now used to map genesin a wide variety of organisms.

17.3 Extranuclear Inheritance:Organelle Genomes

In the previous section, we examined the inheritance patternsof linked genes that violate the law of independent assortment.In this section, we will explore inheritance patterns that violatethe law of segregation. Gene transmission may defy this lawbecause some genes are not found on the chromosomes in thecell nucleus. The segregation of genes is explained by the pair-ing and segregation of homologous chromosomes during meio-sis; genes found elsewhere in the cell do not segregate in thesame way. The transmission of genes that are located outsidethe cell nucleus is called extranuclear inheritance.

Two important types of extranuclear inheritance patternsinvolve genes that are found in mitochondria and chloroplasts(Figure 17.6). Extranuclear inheritance is also called cytoplas-mic inheritance because these organelles are in the cytoplasmof the cell. As we discussed in Chapter 6, mitochondria andchloroplasts are found in eukaryotic cells because of an ancientendosymbiotic relationship. They contain their own genetic ma-terial, or genomes. Although these organelle genomes are muchsmaller than nuclear genomes, researchers have discovered thatthey are critically important in the phenotypes of organisms. Inplants, for example, the chloroplast genome carries many genesthat are vital for photosynthesis. Mitochondrial genes are criti-cal for respiration. In humans, mutations in the mitochondrialgenome may cause inherited diseases. In this section, we willexamine the transmission patterns observed for genes found inthe chloroplast and mitochondrial genomes and consider howmutations in these genes may affect an individual’s traits.

Chloroplast Genomes Are OftenMaternally Inherited

One of the first experiments showing an extranuclear inheri-tance pattern was carried out by Carl Correns in 1909. Corrensdiscovered that leaf pigmentation in the four-o’clock plant(Mirabilis jalapa) follows a pattern of inheritance that does notobey Mendel’s law of segregation. Four-o’clock leaves may begreen, white, or variegated, as shown in Figure 17.7. Correns ob-served that the pigmentation of the offspring depended solely onthe pigmentation of the maternal parent, a phenomenon calledmaternal inheritance. If the female parent had white leaves,

all of the offspring had white leaves. Similarly, if the female wasgreen, so were all of the offspring. The offspring of a variegatedfemale parent could be green, white, or variegated.

At the time, Correns did not understand that chloroplastscontain some genes. We now know that the pigmentation offour-o’clock leaves can be explained by the occurrence of genet-ically different types of chloroplasts in the leaf cells. As dis-cussed in Chapter 8, chloroplasts are the site of photosynthesis,and their green color is due to the presence of the pigment calledchlorophyll. Certain genes required for chlorophyll synthesisare found within the chloroplast DNA. The green phenotype isdue to the presence of chloroplasts that have normal genes andsynthesize the usual quantity of chlorophyll. The white phe-notype is caused by a mutation in a gene within the chloroplastDNA that prevents the synthesis of most of the chlorophyll.


Chloroplast genome

Nuclear genome

Mitochondrial genome

Nuclear genome

Mitochondrial genome

(a) An animal cell

(b) A plant cell

Figure 17.6 The locations of genetic material in animal andplant cells. The chromosomes in the cell nucleus are collectivelyknown as the nuclear genome. Mitochondria and chloroplasts havesmall circular chromosomes, which are called the mitochondrialand chloroplast genomes.





(Enough chlorophyll is made for the plant to survive.) The varie-gated phenotype occurs in leaves that have a mixture of the twotypes of chloroplasts.

Leaf pigmentation follows a maternal inheritance patternbecause the chloroplasts in four o’clocks are inherited onlythrough the cytoplasm of the egg (Figure 17.8). During plant fer-tilization, a sperm cell from a pollen grain fertilizes an egg cellto create a zygote, which eventually develops into a plant. Infour o’clocks, the egg cell contains several proplastids that areinherited by the offspring, while the sperm cell does not con-tribute any proplastids. As discussed in Chapter 4, proplastidsdevelop into various types of plastids, including chloroplasts.Thus, the phenotype of a four-o’clock plant depends on thetypes of proplastids it inherits from the maternal parent. If thematernal parent transmits only normal proplastids, all offspringwill have green leaves (Figure 17.8a). Alternatively, if the ma-ternal parent transmits only mutant proplastids, all offspringwill have white leaves (Figure 17.8b). The genetic compositionof the paternal parent does not affect the outcome. Because anegg cell contains several proplastids, an offspring from a varie-gated maternal parent may inherit only normal proplastids, only


Normal proplastid willproduce chloroplasts with anormal amount of greenpigment.

Eggcell

(a) Egg cell from a maternal parent with green leaves

(c) Possible egg cells from a maternal parent with variegated leaves

(b) Egg cell from a maternal parent with white leaves

Mutant proplastid willproduce chloroplastswith very little pigment.

Figure 17.8 Plastid composition of egg cells from green,white, and variegated four-o’clock plants. In this drawingof four-o’clock egg cells, normal proplastids are representedas green and mutant proplastids as white. Proplastids do notdifferentiate into chloroplasts in egg cells, and they are notactually green. (a) A green plant produces eggs carrying normalproplastids. (b) A white plant produces eggs carrying mutantproplastids. (c) A variegated plant produces eggs that maycontain either or both types of proplastids.

All white offspring

Green, white, or variegated offspring

Reciprocal cross of cross 1

All green offspring

All green offspring

Reciprocal cross of cross 2

Cross 1

Cross 2

�

�

�

�

Correns’ crosses

Figure 17.7 Maternal inheritance in the four-o’clock plant.The genes for green pigment synthesis in plants are part of thechloroplast genome. The white phenotype in four o’clocks isdue to chloroplasts with a mutant allele that greatly reducesgreen pigment production. The variegated phenotype is due toa mixture of normal and mutant chloroplasts. In four o’clocks,the egg contains all of the plastids that are inherited by theoffspring, so the phenotype of the offspring is determined bythe female parent.

Biological inquiry: In this example, where is the gene located thatcauses the green color of four-o’clock leaves? How is this genetransmitted from parent to offspring?





mutant proplastids, or a mixture of normal and mutant proplas-tids. Consequently, the offspring of a variegated maternal parentcan be green, white, or variegated individuals (Figure 17.8c).

The variegated phenotype is due to segregation events thatoccur after fertilization. As a zygote containing both types ofchloroplasts divides to produce a multicellular plant, some cellsmay receive mostly normal chloroplasts. Further division ofthese cells gives rise to a patch of green tissue. Alternatively, asa matter of chance, other cells may receive mostly mutant chloro-plasts that are defective in chlorophyll synthesis. This results ina patch of tissue that is white.

In most species of plants, the egg cell provides most of thezygote’s cytoplasm, while the much smaller male gamete oftenprovides little more than a nucleus. Therefore, chloroplasts aremost often inherited via the egg. In seed-bearing plants, mater-nal inheritance of chloroplasts is the most common transmis-sion pattern. However, certain species exhibit a pattern calledbiparental inheritance, in which both the pollen and the eggcontribute chloroplasts to the offspring. Others exhibit paternalinheritance, in which only the pollen contributes these orga-nelles. For example, most types of pine trees show paternal in-heritance of chloroplasts.

Mitochondrial Genomes Are Maternally Inheritedin Humans and Most Other Species

Mitochondria are found in nearly all eukaryotic species. Similarto the transmission of chloroplasts in plants, maternal inheri-tance is the most common pattern of mitochondrial transmis-sion in eukaryotic species, although some species do exhibitbiparental or paternal inheritance. The mitochondrial genomeof many mammalian species has been analyzed and usuallycontains a total of 37 genes. Twenty-four genes encode tRNAsand rRNAs, which are needed for translation inside the mito-chondrion. Thirteen genes encode proteins that are involved inoxidative phosphorylation. As discussed in Chapter 7, the pri-mary function of the mitochondrion is the synthesis of ATP viaoxidative phosphorylation.

In humans, as in most species, mitochondria are maternallyinherited. Researchers have discovered that mutations in humanmitochondrial genes can cause a variety of rare diseases (Table17.2). These are usually chronic degenerative disorders that af-fect the brain, eyes, heart, muscle, kidney, and endocrine glands.For example, Leber’s hereditary optic neuropathy (LHON) affectsthe optic nerve. It may lead to the progressive loss of vision inone or both eyes. LHON can be caused by a mutation in one ofseveral different mitochondrial genes.

17.4 X Inactivation, GenomicImprinting, and MaternalEffect

We will end our discussion of complex inheritance patterns byconsidering examples in which the timing and control of geneexpression create inheritance patterns that are determined by

the sex of the individual or by the sex of the parents. The firsttwo patterns, called X inactivation and genomic imprinting, aretypes of epigenetic inheritance. In epigenetic inheritance, mod-ification of a gene or chromosome during egg formation, spermformation, or early stages of embryo growth alters gene expres-sion in a way that is fixed during an individual’s lifetime. Epi-genetic changes permanently affect the phenotype of the in-dividual, but they are not permanent over the course of manygenerations and they do not change the actual DNA sequence.For example, a gene may undergo an epigenetic change that in-activates it for an individual’s entire life, so it is never expressedin that individual. However, when the same individual makesgametes, the gene may become activated and remain activeduring the lifetime of an offspring that inherits the gene.

At the end of this section, we will also consider genes thatexhibit a bizarre inheritance pattern called the maternal effect,in which the genotype of the mother directly determines the phe-notype of her offspring. Surprisingly, for maternal effect genes,the genotypes of the father and of the offspring themselves donot affect the offspring’s phenotype. As you will learn, this phe-nomenon is explained by the accumulation of gene products thatthe mother provides to her developing eggs.

In Female Mammals, One X ChromosomeIs Inactivated in Each Somatic Cell

In 1961, the British geneticist Mary Lyon proposed the phenome-non of X inactivation, in which one X chromosome in the somaticcells of female mammals is inactivated, meaning that its genes


Table 17.2 Examples of Human MitochondrialDiseases

Disease Description

Leber’s hereditary Caused by a mutation in one of severaloptic neuropathy mitochondrial genes that encode electron-

transport proteins. The main symptom is lossof vision.

Neurogenic muscle Caused by a mutation in a mitochondrial geneweakness that encodes a subunit of mitochondrial ATP

synthase, which is required for ATP synthesis.Symptoms involve abnormalities in the nervoussystem that affect the muscles and eyes.

Mitochondrial Mutations in mitochondrial genes that encodeencephalomyopathy, tRNAs for leucine and lysine. Symptoms includelactic acidosis, and strokelike episodes, secretion of lactic acid intostrokelike episodes the bloodstream, seizures, migraine headaches,

and lack of coordination.

Maternal A mutation in a mitochondrial gene thatmyopathy and encodes a tRNA for leucine. The primarycardiomyopathy symptoms involve muscle abnormalities, most

notably in the heart.

Myoclonic epilepsy A mutation in a mitochondrial gene thatand ragged-red encodes a tRNA for lysine. Symptoms includemuscle fibers epilepsy, dementia, blindness, deafness, and

heart and kidney malfunctions.





are not expressed. The Lyon hypothesis, as X inactivation alsocame to be known, was based on two lines of evidence. The firstevidence came from microscopic studies of mammalian cells. In1949, Murray Barr and Ewart Bertram identified a highly con-densed structure in the cells of female cats that was not found inthe cells of male cats. This structure was named a Barr body afterone of its discoverers (Figure 17.9). In 1960, Susumu Ohno cor-rectly proposed that a Barr body is a highly condensed X chro-mosome. Lyon’s second line of evidence was the inheritancepattern of variegated coat colors in certain mammals. A classiccase is the calico cat, which has randomly distributed patchesof black and orange fur (Figure 17.10a).

According to the Lyon hypothesis, the calico pattern is ex-plained by the permanent inactivation of one X chromosome ineach cell that forms a patch of the cat’s skin, as shown in Fig-ure 17.10b. The gene involved is an X-linked gene that occursas an orange allele, XO, and a black allele, XB. A female cat thatis heterozygous for this gene will be calico. (The white under-side is due to a dominant allele of a different autosomal gene.)At an early stage of embryonic development, one of the twoX chromosomes is randomly inactivated in each of the cat’ssomatic cells, including those that will give rise to the hair-producing skin cells. As the embryo grows and matures, thepattern of X inactivation is maintained during subsequent celldivisions. For example, skin cells derived from a single embry-onic cell in which the XB-carrying chromosome has been inacti-vated will produce a patch of orange fur, because they expressonly the XO allele that is carried on the active chromosome.Alternatively, a group of skin cells in which the chromosomecarrying XO has been inactivated will express only the XB allele,producing a patch of black fur. Because the primary event ofX inactivation is a random process that occurs at an early stageof development, the result is an animal with randomly distrib-uted patches of black and orange fur.

In female mammals that are heterozygous for X-linkedgenes, approximately half of their somatic cells will express oneallele, while the rest of their somatic cells will express the otherallele. These heterozygotes are called mosaics because theyare composed of two types of cells, analogous to the different-colored pieces in the pictures called mosaics. The phenomenon


Barr body

Figure 17.9 X-chromosome inactivation in female mammals.This light micrograph shows the nucleus of a human female cell. Thelabel shows the Barr body, a condensed, inactivated X chromosomefound just inside the nuclear envelope in the somatic cells offemale mammals.

O B

O BO B O B

O

O

OO

OO

B O B

B

B

B

B

O B

O BO B

Barr bodies

Orange fur allele

(a) Calico cat

Black fur allele

In the early embryo,all X chromosomesare initially active.

In each embryoniccell, random inactivation occursfor one of the Xchromosomes, whichbecomes a Barr body.

As developmentproceeds, the patternof X inactivation ismaintained duringcell division.

(b) Process of X inactivation

1

2

3

Figure 17.10 Random X-chromosome inactivation in acalico cat. (a) A calico cat. (b) X inactivation during embryonicdevelopment. The calico pattern is due to random X-chromosomeinactivation in a female that is heterozygous for the X-linkedgene with black and orange alleles. The cells at the top of thisfigure represent a small mass of cells making up the very earlyembryo. In these cells, both X chromosomes are active. At anearly stage of embryonic development, one X chromosome israndomly inactivated in each cell. The initial inactivation patternis maintained in the descendents of each cell as the embryomatures into an adult. The pattern of orange and black fur inthe adult cat reflects the pattern of X inactivation in the embryo.

Biological inquiry: If a female cat is homozygous for the orangeallele, would it show a calico phenotype?





of mosaicism is readily apparent in calico cats, in which thealleles affect fur color. Likewise, human females who are het-erozygous for X-linked genes are mosaics, with one allele ex-pressed in some cells and the alternative allele in other cells.Women who are heterozygous for recessive X-linked allelesusually show the dominant trait because the expression of thedominant allele in 50% of their cells is sufficient to produce thedominant phenotype.

On rare occasions, a female who is heterozygous for a reces-sive X-linked disease-causing allele may show mild or even se-vere disease symptoms. Because the pattern of X-chromosomeinactivation is random, there will be a small percentage of het-erozygous women who happen to inactivate the X chromo-some carrying the normal allele in a large percentage of theircells, as a matter of bad luck. As an example, let’s consider therecessive X-linked form of hemophilia that we discussed inChapter 16. This type of hemophilia is caused by a defect in agene that encodes a blood-clotting factor, called factor VIII,that is made by cells in the liver and secreted into the blood-stream. X inactivation in humans occurs when an embryo is 10days old. At this stage, the liver contains only about a dozencells. In most females who are heterozygous for the normaland hemophilia alleles, roughly half of their liver cells willexpress the normal allele. However, on rare occasions, all ormost of the dozen embryonic liver cells might happen to inac-tivate the X chromosome carrying the dominant normal allele.Following growth and development, such a female will have avery low level of factor VIII and as a result will show symptomsof hemophilia.

At this point, you may be wondering why X inactivationoccurs. Researchers have proposed that X inactivation achievesdosage compensation between male and female mammals. TheX chromosome carries many genes, while the Y chromosome hasonly a few. The inactivation of one X chromosome in the femalereduces the number of expressed copies (doses) of X-linked genesfrom two to one. As a result, the expression of X-linked genes infemales and males is roughly equal.

The X Chromosome Has an X InactivationCenter That Controls Compaction into aBarr Body

After the Lyon hypothesis was confirmed, researchers becameinterested in the genetic control of X inactivation. The cells ofhumans and other mammals have the ability to count their Xchromosomes and allow only one of them to remain active.Additional X chromosomes are converted to Barr bodies. In nor-mal females, two X chromosomes are counted and one is inac-tivated. In normal males, one X chromosome is counted andnone inactivated. On occasion, however, people are born withabnormalities in the number of their sex chromosomes. In thesedisorders, known as Turner syndrome, Triple X syndrome, andKlinefelter syndrome, the cells inactivate the number of X chro-mosomes necessary to leave a single active chromosome.

Chromosome Number ofPhenotype Composition Barr Bodies

Normal female XX 1

Normal male XY 0

Turner syndrome (female) XO 0

Triple X syndrome (female) XXX 2

Klinefelter syndrome (male) XXY 1

Although the genetic control of inactivation is not entirelyunderstood at the molecular level, a short region on the X chro-mosome called the X inactivation center (Xic) is known toplay a critical role. Eeva Therman and Klaus Patau identified Xicfrom its key role in X inactivation. The counting of human Xchromosomes is accomplished by counting the number of Xics.The Xic on each X chromosome is necessary for inactivation tooccur. Therman and Patau found that in cells with two X chro-mosomes, if one of them is missing its Xic due to a chromo-some mutation, neither X chromosome will be inactivated. Thisis a lethal condition for a human female embryo.

The expression of a specific gene within the X inactivationcenter is required for compaction of the X chromosome intoa Barr body. This gene, discovered in 1991, is named Xist (forX inactive specific transcript). The Xist gene product is a longRNA molecule that does not encode a protein. Instead, the roleof Xist RNA is to coat one of the two X chromosomes duringthe process of X inactivation. The Xist gene on the inactivatedX chromosome continues to be expressed after other genes onthis chromosome have been silenced.

The process of X inactivation can be divided into threephases: initiation, spreading, and maintenance (Figure 17.11).During initiation, one of the X chromosomes is targeted for in-activation. This chromosome is inactivated during the spread-ing phase, so called because inactivation begins near the Xinactivation center and spreads in both directions along thechromosome. Spreading requires the transcription of the Xistgene and coating of the X chromosome with Xist RNA. Aftercoating, proteins associate with the Xist RNA and promote com-paction of the chromosome into a Barr body. Maintenance refersto replication of the compacted chromosome during subsequentcell divisions. While initiation and spreading occur only duringembryonic development, maintenance occurs throughout theindividual’s life. Continued activity of the Xist gene on an in-activated X chromosome maintains this chromosome as a Barrbody during cell division. Whenever a somatic cell divides ina female mammal, the Barr body is replicated to produce twoBarr bodies.

The Transcription of an Imprinted GeneDepends on the Sex of the Parent

As we have seen, X inactivation is a type of epigenetic inheritancein which a chromosome is modified in the early embryo, perma-nently altering gene expression in that individual. Other typesof epigenetic inheritance occur in which genes or chromosomes






are modified in the gametes of a parent, permanently alteringgene expression in the offspring. Genomic imprinting refersto a phenomenon in which a segment of DNA is imprinted, ormarked, in a way that affects gene expression throughout thelife of the individual who inherits that DNA.

Genomic imprinting occurs in numerous species, includinginsects, plants, and mammals. Imprinting may involve a singlegene, a part of a chromosome, an entire chromosome, or evenall of the chromosomes inherited from one parent. It is perma-nent in the somatic cells of a given individual, but the markingof the DNA is altered from generation to generation. Imprintedgenes do not follow a Mendelian pattern of inheritance becauseimprinting causes the offspring to distinguish between mater-nally and paternally inherited alleles. Depending on how a par-

ticular gene is marked by each parent, the offspring will expresseither the maternal or the paternal allele, but not both.

Let’s consider a specific example of imprinting that involvesa gene called Igf-2 that is found in mice and other mammals.This gene encodes a growth hormone called insulin-like growthfactor 2 that is needed for proper growth. If a normal copy ofthis gene is not expressed, a mouse will be dwarf. The Igf-2 geneis known to be located on an autosome, not on a sex chromo-some. Because mice are diploid, they have two copies of thisgene, one from each parent.

Researchers have discovered that mutations can occur in theIgf-2 gene that block the function of the Igf-2 hormone. Whenmice carrying normal or mutant alleles are crossed to each other,a bizarre result is obtained (Figure 17.12). If the male parent


To beinactivated

Coating by Xist RNAand additional proteins

XicXic XicXic

Barr body

Furtherspreading

1 2 3 Maintenance: Occurs from embryonic development through adult life. The inactivated X chromosome is maintainedas a Barr body during subsequent cell divisions.

Spreading: Occurs during embryonic development. It begins at the Xic and progresses toward both ends until the entire chromosome is inactivated. The Xist gene, located within the Xic, encodes an RNA that coats the X chromosome and promotes its compaction into a Barr body.

Initiation: Occurs during embryonic development. The X inactivation centers (Xics) are counted and one of the X chromosomes is targeted for inactivation.

Figure 17.11 The process of X inactivation.

Igf-2m Igf-2m(homozygous dwarf)

Igf-2 Igf-2(homozygous normal)

Igf-2 Igf-2(homozygous normal)

Igf-2m Igf-2m(homozygous dwarf)

Igf-2 Igf-2m(heterozygous)

Igf-2 Igf-2m(heterozygous)

� �Parents

Offspring genotype

Igf-2Igf-2m

normal allelemutant allelesilenced allele (from female parent)expressed allele (from male parent)

Allele that is transcribed in offspring

Phenotype

Igf-2(normal)

Normal

Igf-2m(nonfunctional)

Dwarf

Figure 17.12 An example of genomic imprinting in the mouse. In the cross on the left, a homozygous male with the normal Igf-2allele is crossed to a homozygous female carrying a defective allele, Igf-2m. An offspring is phenotypically normal because the paternalallele is expressed. In the cross on the right, a homozygous male carrying the defective allele is crossed to a homozygous normal female.In this case, an offspring is dwarf because the paternal allele is defective and the maternal allele is not expressed.





is homozygous for the normal allele and the female is homozy-gous for the mutant allele, all the offspring grow to a normal size.In contrast, if the male is homozygous for the mutant allele andthe female is homozygous for the normal allele, all the offspringare dwarf. The reason this result is so surprising is that the nor-mal and dwarf offspring have the same genotype but differentphenotypes! These phenotypes are not the result of any externalinfluence on the offspring’s development. Rather, the allele thatis expressed in their somatic cells depends on which parent con-tributed which allele. In mice, the Igf-2 gene inherited from themother is imprinted in such a way that it cannot be transcribedinto mRNA. Therefore, only the paternal gene is expressed. Themouse on the left side of Figure 17.12 is normal because it ex-presses a functional paternal gene. In contrast, the mouse on theright is dwarf because the paternal gene is a mutant allele thatresults in a nonfunctional hormone. In both cases, the maternalgene is inactive due to imprinting.

Why is the maternal gene not transcribed into mRNA? Toanswer this question we need to consider the molecular func-tion of genes. As discussed in Chapter 13, the attachment ofmethyl (¬CH3) groups to the bases of DNA can alter gene tran-scription. For most genes, methylation silences gene expressionby causing the DNA to become more compact. For a few genes,methylation may enhance gene expression by attracting activa-tor proteins to the promoter. Researchers have discovered thatDNA methylation is the marking process that occurs during theimprinting of certain genes, including the Igf-2 gene.

Figure 17.13 shows the imprinting process in which a ma-ternal gene is methylated. The left side of the figure follows themarking process during the life of a female individual; the rightside follows the same process in a male. Both individuals re-ceived a methylated gene from their mother and a nonmethylatedcopy of the same gene from their father. Via cell division, the zy-gote develops into a multicellular organism. Each time a somaticcell divides, enzymes in the cell maintain the methylation of thematernal gene, while the paternal gene remains unmethylated.If the methylation inhibits transcription of this gene, only thepaternal copy will be expressed in the somatic cells of both themale and female offspring.

The methylation state of an imprinted gene may be alteredwhen individuals make gametes. First, as shown in Figure 17.13,the methylation is erased. Next, the gene may be methylatedagain, but that depends on whether the individual is a female ormale. In females making eggs, both copies of the gene are methy-lated; in males making sperm, neither copy is methylated. Whenwe consider the effects of methylation over the course of twoor more generations, we can see how this phenomenon createsan epigenetic transmission pattern. The male in Figure 17.13has inherited a methylated gene from his mother that is tran-scriptionally silenced in his somatic cells. Although he does notexpress this gene during his lifetime, he can pass on an active,nonmethylated copy of this exact same gene to his offspring.

Genomic imprinting is a recently discovered phenomenonthat has been shown to occur for a few genes in mammals. Forsome genes, such as Igf-2, the maternal allele is silenced, whilefor other genes the paternal allele is silenced. Biologists are stilltrying to understand the reason for this curious marking process.


Erasure Erasure

New methylation No methylation

Formationof eggs

Formationof sperm

Allsomaticcells

Allsomaticcells

Female offspring Male offspring

Paternalchromosome

Maternalchromosome

Maternalchromosome

Paternalchromosome

Female gamete-producing cell

Male gamete-producing cell

–CH3 –CH3 –CH3








1

2

3

After fertilization, somatic cells retain the methylation pattern inherited from the parents.

During gamete formation, methylation is erased.

During egg formation, the gene is always methylated, while during sperm formation it is not.

Figure 17.13 Genomic imprinting via DNA methylation.The cells at the top of this figure have a methylated geneinherited from the mother and a nonmethylated version of thesame gene inherited from the father. This pattern of methylationis the same in male and female offspring and is maintained intheir somatic cells. The methylation is erased during gameteformation, but in females the gene is methylated again at a laterstage in the formation of eggs. Therefore, females always transmita methylated, transcriptionally silent copy of this gene, whilemales transmit a nonmethylated, active copy.





For Maternal Effect Genes, the Genotypeof the Mother Determines the Phenotypeof the Offspring

In epigenetic inheritance, genes are altered in ways that affecttheir expression in an individual or the individual’s offspring.As we have seen, some of these alterations produce strange in-heritance patterns, in which organisms with the same genotypehave different phenotypes. Another strange inheritance pattern,with a very different explanation, involves a category of genescalled maternal effect genes.

Inheritance patterns due to maternal effect genes were firstidentified in the 1920s by A. E. Boycott, in his studies of the fresh-water snail Lymnaea peregra. In this species, the shell and inter-nal organs can be arranged in either a right-handed (dextral) or aleft-handed (sinistral) direction. The dextral orientation is morecommon and is dominant to the sinistral orientation. Whether asnail’s body curves in a dextral or a sinistral direction dependson the pattern of cell division immediately following fertiliza-tion. Figure 17.14 shows the results of Boycott’s crosses of true-breeding strains of snails with either a dextral or a sinistral ori-entation. When a dextral female (DD) was crossed to a sinistralmale (dd), all of the offspring were dextral. However, crossing asinistral female (dd) to a dextral male (DD) produced the oppo-site result: all of the offspring were sinistral. These seeminglycontradictory outcomes could not be explained in terms of Men-delian inheritance.

Alfred Sturtevant later suggested that snail coiling is dueto a maternal effect gene that exists as a dextral (D) and a sin-istral (d) allele. In the cross shown on the left, the P generationfemale is dextral (DD) and the male is sinistral (dd). In thecross on the right, the female is sinistral (dd) and the male isdextral (DD). In either case, the F1 offspring are Dd. When theF1 individuals from these two crosses are mated to each other, agenotypic ratio of 1 DD : 2 Dd : 1 dd is predicted for the F2 gen-eration. Because the D allele is dominant to the d allele, aMendelian inheritance pattern would produce a 3:1 phenotypicratio of dextral to sinistral snails. Instead, the snails of the F2

generation were all dextral. To explain this observed result, Stur-tevant proposed that the phenotype of the F2 offspring dependedsolely on the genotype of the F1 mother. Because the F1 motherswere Dd, and the D allele is dominant, the F2 offspring weredextral even if their genotype was dd!

Sturtevant’s hypothesis is supported by the ratio of pheno-types seen in the F3 generation. When members of the F2 gen-eration were crossed, the F3 generation exhibited a 3:1 ratio ofdextral to sinistral snails. These F3 phenotypes reflect the geno-types of the F2 mothers. The ratio of genotypes for the F2 fe-males was 1 DD : 2 Dd : 1 dd. The DD and Dd females produceddextral offspring, while the dd females produced sinistral off-spring. This is consistent with the 3:1 phenotypic ratio in theF3 generation.

The peculiar inheritance pattern of maternal effect genes canbe explained by the process of egg maturation in female animals(Figure 17.15). Maternal cells called nurse cells surround a de-

veloping egg cell and provide it with nutrients. Within thesediploid nurse cells, both copies of a maternal effect gene areactivated to produce their gene products. The gene products aretransported into the egg, where they persist for a significant timeduring embryonic development. The D and d gene products in-fluence the pattern of cell division during the early stages of thesnail’s embryonic development. If an egg receives only the Dgene product, the snail will develop a dextral orientation, whilean egg that receives only the d gene product will produce a


P

F1

F2

F3

�

�

DD dd

�

DDdd

DdAll dextral

DdAll sinistral

1 DD : 2 Dd : 1 ddAll dextral

3 dextral : 1 sinistral

Cross to each other

Males and females

Males and females

Figure 17.14 The inheritance of snail coiling direction asan example of a maternal effect gene. In the snails shown inthis experiment, the direction of body coiling is controlled by asingle pair of genes. D (dextral, or right-handed) is dominant to d(sinistral, or left-handed). The genotype of the mother determinesthe phenotype of the offspring. A DD or Dd mother will producedextral offspring and a dd mother will produce sinistral offspring,regardless of the genotypes of the father and of the offspringthemselves.

Biological inquiry: An offspring has a genotype of Dd and coilsto the left. What is the genotype of its mother?





snail with a sinistral orientation. If an egg receives both D andd gene products, the snail will be dextral because the D geneproduct is dominant over d. In this way, the gene products ofnurse cells, which are determined by the mother’s genotype, in-fluence the development of the offspring.

Several dozen maternal effect genes have been identified inexperimental organisms, such as Drosophila. Recently, they havealso been found in mice and humans. As we will discuss inChapter 19, the products of maternal effect genes are criticallyimportant in the early stages of animal development.


Mother is DD.

All offspring are dextral because the egg received the gene products of the D allele.

Mother is Dd. Mother is dd.

All offspring are dextral because the egg received the gene products of the D and d alleles, but the D gene products are dominant.

All offspring are sinistral because the egg received the gene products of the d allele.

DD DD

DD

DD DD

DDD geneproducts

dddd

dd

dd dd

ddd geneproducts

DdDd

Dd

Dd Dd

DdD and dgeneproducts

Nurse cells

Egg

Figure 17.15 The mechanism of maternal effect in snail coiling. In this simplified diagram, the mother’s diploid nurse cellstransfer gene products to the egg as it matures. These gene products persist after fertilization, affecting development of the early embryo.If the nurse cells are DD or Dd, they will transfer the dominant D gene product to the egg, causing the offspring to be dextral. If the nursecells are dd, only the d gene product will be transferred to the egg and the offspring will be sinistral.

• A variety of inheritance patterns are more complex than Mendelhad realized. Many of these do not obey one or both of his lawsof inheritance. (Table 17.1)

17.1 Gene Interactions• When the alleles of one gene mask the effects of the alleles of a

different gene, this type of gene interaction is called epistasis.(Figure 17.1)

• Quantitative traits such as height and weight are polygenic, whichmeans that several genes govern the trait. Often, the alleles ofsuch genes contribute in an additive way to the phenotype. Thisproduces continuous variation in the trait, which is graphed asa bell curve. (Figure 17.2)

17.2 Genes on the Same Chromosome: Linkage,Recombination, and Mapping

• When two different genes are on the same chromosome, they aresaid to be linked. Linked genes tend to be inherited as a unit,unless crossing over separates them. (Figures 17.3, 17.4)

• The percentage of offspring produced in a two-factor testcross canbe used to map the relative locations of genes along a chromosome.(Figure 17.5)

17.3 Extranuclear Inheritance: Organelle Genomes• Mitochondria and chloroplasts carry a small number of genes.

The inheritance of such genes is called extranuclear inheritance.(Figure 17.6)

• Chloroplasts in the four-o’clock plant are transmitted via the egg,a pattern called maternal inheritance. (Figures 17.7, 17.8)

• Several human diseases are known to be caused by mutations inmitochondrial genes, which follow a maternal inheritance pattern.(Table 17.2)

17.4 X Inactivation, Genomic Imprinting,and Maternal Effect

• Epigenetic inheritance refers to patterns in which a gene isinactivated during the life of an organism, but not over the courseof many generations.

• X inactivation in mammals occurs when one X chromosome israndomly inactivated in females. If the female is heterozygousfor an X-linked gene, this can lead to a variegated phenotype.(Figures 17.9, 17.10)

• X inactivation occurs in three phases: initiation, spreading, andmaintenance. (Figure 17.11)

• Imprinted genes are inactivated by one parent but not both. Theoffspring expresses only one of the two alleles. (Figure 17.12)

• During gamete formation, methylation of a gene from one parentis a mechanism to achieve imprinting. (Figure 17.13)






• For maternal effect genes, the genotype of the mother determines thephenotype of the offspring. This is explained by the phenomenon thatthe mother’s nurse cells contribute gene products to egg cells thatare needed for early stages of development. (Figures 17.14, 17.15)

1. Quantitative traits such as height and weight are governed byseveral genes that usually contribute in an additive way to thetrait. This is calleda. independent assortment.b. discontinuous inheritance.c. maternal inheritance.d. linkage.e. polygenic inheritance.

2. When two genes are located on the same chromosome they aresaid to bea. homologous. d. linked.b. allelic. e. polygenic.c. epistatic.

3. Based on the ideas proposed by Morgan, which of the followingstatements concerning linkage is not true?a. Traits determined by genes located on the same chromosome are

likely to be inherited together.b. Crossing over between homologous chromosomes can create new

gene combinations.c. Crossing over is more likely to occur between genes that are closer

together.d. The probability of crossing over depends on the distance between

the genes.e. All but one of the above statements are correct.

4. In genetic linkage mapping, 1 map unit is equivalent toa. 100 base pairs.b. 1 base pair.c. 10% recombination frequency.d. 1% recombination frequency.e. 1% the length of the chromosome.

5. Organelle heredity is possible becausea. gene products may be stored in organelles.b. mRNA may be stored in organelles.c. some organelles contain genetic information.d. conjugation of nuclei occurs before cellular division.e. both a and c.

6. In many organisms, organelles such as the mitochondria are contributedby only the egg. This phenomenon is known asa. biparental inheritance.b. paternal inheritance.c. maternal effect.d. maternal inheritance.e. both c and d.

7. Modification of a gene during gamete formation or early developmentthat alters the way the gene is expressed during the individual’slifetime is calleda. maternal inheritance.b. epigenetic inheritance.c. epistasis.d. multiple allelism.e. alternative splicing.

8. When a gene is inactivated during gamete formation and that gene ismaintained in an inactivated state in the somatic cells of offspring,such an inheritance pattern is calleda. linkage.b. X inactivation.c. maternal effect.d. genomic imprinting.e. polygenic inheritance.

9. Calico coat pattern in cats is the result ofa. X inactivation. d. genomic imprinting.b. epistasis. e. maternal inheritance.c. organelle heredity.

10. Maternal effect inheritance can be explained bya. gene products that are given to an egg by the nurse cells.b. the methylation of genes during gamete formation.c. the spreading of X inactivation from the Xic locus.d. the inheritance of alleles that contribute additively to a trait.e. none of the above.

1. Define linkage and linkage group.

2. Explain extranuclear inheritance and give two examples.

3. Define genomic imprinting.

1. What hypothesis were Bateson and Punnett testing when conductingthe crosses in the sweet pea?

2. What were the expected results of Bateson and Punnett’s cross?

3. How did the observed results differ from the predicted results? Howdid Bateson and Punnett explain the results of this particular cross?

1. Discuss two types of gene interactions.

2. Discuss the concept of linkage.

www.brookerbiology.comThis website includes answers to the Biological Inquiry questions

found in the figure legends and all end-of-chapter questions.

atterns inheritance

Documents