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Learning Objectives Connection for AP® Courses Phenotypes and Genotypes The Punnett Square Approach for a Monohybrid Cross Alternatives to Dominance and Recessiveness References Disclaimer

Learning Objectives

In this section, you will explore the following questions:

What is the relationship between genotypes and phenotypes in dominant and recessive gene systems?
How can a Punnett square be used to calculate expected proportions of genotypes and phenotypes in a monohybrid cross?
How do phenomena such as incomplete dominance, codominance, recessive lethals, multiple alleles, and sex linkage explain deviations from Mendel’s model of inheritance?

Connection for AP® Courses

Connection for AP^® Courses

The characteristics that Mendel evaluated in his pea plants were each expressed as one of two versions, or traits, for example, green peas versus yellow peas). As we will explore in more detail in later chapters, the physical expression of characteristics is accomplished through the expression of genes—sequences of DNA—carried on chromosomes. The genetic makeup of peas consists of two similar, or homologous—remember this term from Chapter 11—copies of each chromosome, one from each parent. Through meiosis, diploid organisms utilize meiosis to produce haploid (1n) gametes that participate in fertilization. For cases in which a single gene controls a single characteristic, such as pea color, a diploid organism has genetic copies that may or may not encode the same version of the characteristic. These gene variations, for example, green peas versus yellow peas—are called alleles.

Different alleles for a given gene in a diploid organism interact to express physical characteristics such as pea color in plants or hairline appearance in humans. The observable traits of an organism are referred to as its phenotype. The organism’s underlying genetic makeup, that is, the combination of alleles, is called its genotype. When diploid organisms carry the same alleles for a given trait, they are said to be homozygous for the genotype; when they carry different alleles, they are said to be heterozygous. For a gene whose expression is Mendelian (Section 12.1), homozygous dominant and heterozygous organisms will look identical, that is, they will have different genotypes but the same phenotype. The recessive allele will only be observed in homozygous recessive individuals.

However, alleles do not always behave in dominant and recessive patterns. In other words, there are exceptions to Mendel’s model of inheritance. For example, incomplete dominance describes situation in which the heterozygote exhibits a phenotype that is intermediate between the homozygous phenotypes (e.g., a pink-flowered offspring is produced from a cross between a red-flowered parent and a white-flowered parent). Codominance describes the simultaneous expression of both of the alleles in the heterozygote (e.g., human blood types). It is also common for more than two alleles of a gene to exist in a population (e.g., variations in sizes of pumpkins). In humans, as in many animals and some plants, females have two X chromosomes, and males have one X chromosome and one Y chromosome. Genes on the X chromosome are X-linked, and males inherit and express only one allele for the gene (e.g., hemophilia, color-blindness). Some alleles can also be lethal, so their phenotype will never be observed.

Many human genetic disorders, including albinism, cystic fibrosis, and Huntington’s disease can be explained on the basis of simple Mendelian inheritance patterns created by pedigree analysis. In later chapters, we will learn how DNA analysis can be used to diagnose genetic disorders. Punnett squares are useful tools that apply the rules of probability and meiosis to predict the possible outcomes of genetic crosses. Test crosses are done to determine whether or not an individual is homozygous or heterozygous by crossing the individual with a homozygous recessive.

Information presented and the examples highlighted in the section support concepts outlined in Big Idea 3 of the AP^® Biology Curriculum Framework. The Learning Objectives listed in the Curriculum Framework provide a transparent foundation for the AP^® Biology course, an inquiry-based laboratory experience, instructional activities, and AP^® exam questions. A Learning Objective merges required content with one or more of the seven Science Practices.

Big Idea 3	Living systems store, retrieve, transmit, and respond to information essential to life processes.
Enduring Understanding 3.A	Heritable information provides for continuity of life.
Essential Knowledge	3.A.3 The chromosomal basis of inheritance proposed by Mendel provides an understanding of the pattern of passage of genes from parent to offspring.
Science Practice	1.1 The student can create representations and models of natural or man-made phenomena and systems in the domain.
Science Practice	7.2 The student can connect concepts in and across domain(s) to generalize or extrapolate in and/or across enduring understandings and/or big ideas.
Learning Objective	3.12 The student is able to construct a representation (e.g., Punnett square) that connects the process of meiosis to the passage of traits from parent to offspring.
Essential Knowledge	3.A.3 The chromosomal basis of inheritance proposed by Mendel provides an understanding of the pattern of passage of genes from parent to offspring.
Science Practice	3.1 The student can pose scientific questions.
Learning Objective	3.13 The student is able to pose questions about ethical, social, or medical issues surrounding human genetic disorders.
Essential Knowledge	3.A.3 The chromosomal basis of inheritance proposed by Mendel provides an understanding of the pattern of passage of genes from parent to offspring.
Science Practice	2.2 The student can apply mathematical routines to quantities that describe natural phenomena.
Learning Objective	3.14 The student is able to apply mathematical routines to determine Mendelian patterns of inheritance provided by data sets.
Essential Knowledge	3.A.4 The inheritance patterns of many traits cannot be explained by simple Mendelian genetics.
Science Practice	6.5 The student can evaluate alternative scientific explanations.
Learning Objective	3.15 The student is able to explain deviations from Mendel’s model of the inheritance of traits.
Essential Knowledge	3.A.4 The inheritance patterns of many traits cannot be explained by simple Mendelian genetics.
Science Practice	6.3 The student can articulate the reasons that scientific explanations and theories are refined or replaced.
Learning Objective	3.16 The student is able to explain how the inheritance pattern of many traits cannot be accounted for by Mendelian genetics.
Essential Knowledge	3.A.4 The inheritance patterns of many traits cannot be explained by simple Mendelian genetics.
Science Practice	1.2 The student can describe representations and models of natural or man-made phenomena and systems in the domain.
Learning Objective	3.17 The student is able to describe representations of an appropriate example of inheritance patterns that cannot be explained by Mendel’s model of the inheritance of traits.

The Science Practices Assessment Ancillary contains additional test questions for this section that will help you prepare for the AP exam. These questions address the following standards:

[APLO 3.12]
[APLO 3.14]
[APLO 3.16]
[APLO 3.11]
[APLO 3.13]
[APLO 3.17]

The seven characteristics that Mendel evaluated in his pea plants were each expressed as one of two versions, or traits. The physical expression of characteristics is accomplished through the expression of genes carried on chromosomes. The genetic makeup of peas consists of two similar or homologous copies of each chromosome, one from each parent. Each pair of homologous chromosomes has the same linear order of genes. In other words, peas are diploid organisms in that they have two copies of each chromosome. The same is true for many other plants and for virtually all animals. Diploid organisms utilize meiosis to produce haploid gametes, which contain one copy of each homologous chromosome that unite at fertilization to create a diploid zygote.

For cases in which a single gene controls a single characteristic, a diploid organism has two genetic copies that may or may not encode the same version of that characteristic. Gene variants that arise by mutation and exist at the same relative locations on homologous chromosomes are called alleles. Mendel examined the inheritance of genes with just two allele forms, but it is common to encounter more than two alleles for any given gene in a natural population.

Phenotypes and Genotypes

Two alleles for a given gene in a diploid organism are expressed and interact to produce physical characteristics. The observable traits expressed by an organism are referred to as its phenotype. An organism’s underlying genetic makeup, consisting of both physically visible and non expressed alleles, is called its genotype. Mendel’s hybridization experiments demonstrate the difference between phenotype and genotype. When true-breeding plants in which one parent had yellow pods and one had green pods were cross-fertilized, all of the F₁ hybrid offspring had yellow pods. That is, the hybrid offspring were phenotypically identical to the true-breeding parent with yellow pods. However, we know that the allele donated by the parent with green pods was not simply lost because it reappeared in some of the F₂ offspring. Therefore, the F₁ plants must have been genotypically different from the parent with yellow pods.

The P₁ plants that Mendel used in his experiments were each homozygous for the trait he was studying. Diploid organisms that are homozygous at a given gene, or locus, have two identical alleles for that gene on their homologous chromosomes. Mendel’s parental pea plants always bred true because both of the gametes produced carried the same trait. When P₁ plants with contrasting traits were cross-fertilized, all of the offspring were heterozygous for the contrasting trait, meaning that their genotype reflected that they had different alleles for the gene being examined.

Dominant and Recessive Alleles

Our discussion of homozygous and heterozygous organisms brings us to why the F₁ heterozygous offspring were identical to one of the parents, rather than expressing both alleles. In all seven pea-plant characteristics, one of the two contrasting alleles was dominant, and the other was recessive. Mendel called the dominant allele the expressed unit factor; the recessive allele was referred to as the latent unit factor. We now know that these so-called unit factors are actually genes on homologous chromosome pairs. For a gene that is expressed in a dominant and recessive pattern, homozygous dominant and heterozygous organisms will look identical, that is, they will have different genotypes but the same phenotype. The recessive allele will only be observed in homozygous recessive individuals (Table 12.4).

Human Inheritance in Dominant and Recessive Patterns
Dominant Traits	Recessive Traits
Achondroplasia	Albinism
Brachydactyly	Cystic fibrosis
Huntington’s disease	Duchenne muscular dystrophy
Marfan syndrome	Galactosemia
Neurofibromatosis	Phenylketonuria
Widow’s peak	Sickle cell anemia
Wooly hair	Tay-Sachs disease

Table 12.4

Several conventions exist for referring to genes and alleles. For the purposes of this chapter, we will abbreviate genes using the first letter of the gene’s corresponding dominant trait. For example, violet is the dominant trait for a pea plant’s flower color, so the flower-color gene would be abbreviated as V—note that it is customary to italicize gene designations. Furthermore, we will use uppercase and lowercase letters to represent dominant and recessive alleles, respectively. Therefore, we would refer to the genotype of a homozygous dominant pea plant with violet flowers as VV, a homozygous recessive pea plant with white flowers as vv, and a heterozygous pea plant with violet flowers as Vv.

The Punnett Square Approach for a Monohybrid Cross

When fertilization occurs between two true-breeding parents that differ in only one characteristic, the process is called a monohybrid cross, and the resulting offspring are monohybrids. Mendel performed seven monohybrid crosses involving contrasting traits for each characteristic. On the basis of his results in F₁ and F₂ generations, Mendel postulated that each parent in the monohybrid cross contributed one of two paired unit factors to each offspring, and every possible combination of unit factors was equally likely.

To demonstrate a monohybrid cross, consider the case of true-breeding pea plants with yellow versus green pea seeds. The dominant seed color is yellow; therefore, the parental genotypes were YY for the plants with yellow seeds and yy for the plants with green seeds, respectively. A Punnett square, devised by the British geneticist Reginald Punnett, can be drawn that applies the rules of probability to predict the possible outcomes of a genetic cross or mating and their expected frequencies. To prepare a Punnett square, all possible combinations of the parental alleles are listed along the top—for one parent—and side—for the other parent—of a grid, representing their meiotic segregation into haploid gametes. Then the combinations of egg and sperm are made in the boxes in the table to show which alleles are combining. Each box then represents the diploid genotype of a zygote, or fertilized egg, that could result from this mating. Because each possibility is equally likely, genotypic ratios can be determined from a Punnett square. If the pattern of inheritance—dominant or recessive—is known, the phenotypic ratios can be inferred as well. For a monohybrid cross of two true-breeding parents, each parent contributes one type of allele. In this case, only one genotype is possible. All offspring are Yy and have yellow seeds (Figure 12.4).

This illustration shows a monohybrid cross. In the P generation, one parent has a dominant yellow phenotype and the genotype YY, and the other parent has the recessive green phenotype and the genotype yy. Each parent produces one kind of gamete, resulting in an F_{1} generation with a dominant yellow phenotype and the genotype Yy. Self-pollination of the F_{1} generation results in an F_{2} generation with a 3 to 1 ratio of yellow to green peas. One out of three of the yellow pea plants has a dominant gen

Figure 12.4 In the P generation, pea plants that are true-breeding for the dominant yellow phenotype are crossed with plants with the recessive green phenotype. This cross produces F₁ heterozygotes with a yellow phenotype. Punnett square analysis can be used to predict the genotypes of the F₂ generation.

A self-cross of one of the Yy heterozygous offspring can be represented in a 2 × 2 Punnett square because each parent can donate one of two different alleles. Therefore, the offspring can potentially have one of four allele combinations: YY, Yy, yY, or yy (Figure 12.4). Notice that there are two ways to obtain the Yy genotype: a Y from the egg and a y from the sperm, or a y from the egg and a Y from the sperm. Both of these possibilities must be counted. Recall that Mendel’s pea-plant characteristics behaved in the same way in reciprocal crosses. Therefore, the two possible heterozygous combinations produce offspring that are genotypically and phenotypically identical despite their dominant and recessive alleles deriving from different parents. They are grouped together. Because fertilization is a random event, we expect each combination to be equally likely and for the offspring to exhibit a ratio of YY:Yy:yy genotypes of 1:2:1 (Figure 12.4). Furthermore, because the YY and Yy offspring have yellow seeds and are phenotypically identical, applying the sum rule of probability, we expect the offspring to exhibit a phenotypic ratio of 3 yellow:1 green. Indeed, working with large sample sizes, Mendel observed approximately this ratio in every F₂ generation resulting from crosses for individual traits.

Mendel validated these results by performing an F₃ cross in which he self-crossed the dominant- and recessive-expressing F₂ plants. When he self-crossed the plants expressing green seeds, all of the offspring had green seeds, confirming that all green seeds had homozygous genotypes of yy. When he self-crossed the F₂ plants expressing yellow seeds, he found that one-third of the plants bred true, and two-thirds of the plants segregated at a 3:1 ratio of yellow:green seeds. In this case, the true-breeding plants had homozygous (YY) genotypes, whereas the segregating plants corresponded to the heterozygous (Yy) genotype. When these plants self-fertilized, the outcome was just like the F₁ self-fertilizing cross.

The Test Cross Distinguishes the Dominant Phenotype

Beyond predicting the offspring of a cross between known homozygous or heterozygous parents, Mendel also developed a way to determine whether an organism that expressed a dominant trait was a heterozygote or a homozygote. Called the test cross, this technique is still used by plant and animal breeders. In a test cross, the dominant-expressing organism is crossed with an organism that is homozygous recessive for the same characteristic. If the dominant-expressing organism is a homozygote, then all F₁ offspring will be heterozygotes expressing the dominant trait (Figure 12.5). Alternatively, if the dominant expressing organism is a heterozygote, the F₁ offspring will exhibit a 1:1 ratio of heterozygotes and recessive homozygotes (Figure 12.5). The test cross further validates Mendel’s postulate that pairs of unit factors segregate equally.

Visual Connection

In a test cross, a parent with a dominant phenotype but unknown genotype is crossed with a recessive parent. If the parent with the unknown phenotype is homozygous dominant, all of the resulting offspring will have at least one dominant allele. If the parent with the unknown phenotype is heterozygous, fifty percent of the offspring will inherit a recessive allele from both parents and will have the recessive phenotype.

Figure 12.5 A test cross can be performed to determine whether an organism expressing a dominant trait is a homozygote or a heterozygote.

In pea plants, round peas (R) are dominant to wrinkled peas (r).You do a test cross between a pea plant with wrinkled peas (genotype rr) and a plant of unknown genotype that has round peas. You end up with three plants, all which have round peas. From this data, can you tell if the round pea parent plant is homozygous dominant or heterozygous? If the round pea parent plant is heterozygous, what is theprobability that a random sample of three progeny peas will all be round?

The data set is too small to predict the genotype of the round pea plant. Assuming that the unknown parent is heterozygous, the probability of having only round pea plants from a random sample of three progeny will be $\frac{1}{8} .$
The genotype of the unknown round pea plant is Rr. Assuming that the unknown parent is heterozygous, then the probability of having only round pea plants from a random sample of three progeny will be $\frac{1}{4} .$
The genotype of the unknown round pea plant is Rr. Assuming that the unknown parent is heterozygous, the probability of having only round pea plants from a random sample of three progeny will be $\frac{1}{2} .$
The data set is too small to predict the genotype of the round pea plant. The probability of having only round pea plants from a random sample of three progeny will be $\frac{1}{6} .$

Many human diseases are genetically inherited. A healthy person in a family in which some members suffer from a recessive genetic disorder may want to know if he or she has the disease-causing gene and what risk exists of passing the disorder on to his or her offspring. Of course, doing a test cross in humans is unethical and impractical. Instead, geneticists use pedigree analysis to study the inheritance pattern of human genetic diseases (Figure 12.6).

Visual Connection

This is a pedigree of a family that carries the recessive disorder alkaptonuria. In the second generation, an unaffected mother and an affected father have three children. One child has the disorder, so the genotype of the mother must be Aa and the genotype of the father is aa. One unaffected child goes on to have two children, one affected and one unaffected. Because her husband was not affected, she and her husband must both be heterozygous. The genotype of their unaffected child is unknown, and is desi

Figure 12.6 Alkaptonuria is a recessive genetic disorder in which two amino acids, phenylalanine and tyrosine, are not properly metabolized. Affected individuals may have darkened skin and brown urine, and may suffer joint damage and other complications. In this pedigree, individuals with the disorder are indicated in blue and have the genotype aa. Unaffected individuals are indicated in yellow and have the genotype AA or Aa. Note that it is often possible to determine a person’s genotype from the genotype of their offspring. For example, if neither parent has the disorder but their child does, they must be heterozygous. Two individuals on the pedigree have an unaffected phenotype but unknown genotype. Because they do not have the disorder, they must have at least one normal allele, so their genotype gets the “A?” designation.

Figure 12.7

Using the pedigree above, what are the genotypes of the individuals labeled 1, 2, and 3?

1:aa, 2:AA, 3:AA
1:aa, 2:Aa, 3:Aa
1:aa, 2:Aa, 3:AA
1:Aa, 2:Aa, 3:Aa

Alternatives to Dominance and Recessiveness

Mendel’s experiments with pea plants suggested that: (1) two units or alleles exist for every gene; (2) alleles maintain their integrity in each generation—no blending—and (3) in the presence of the dominant allele, the recessive allele is hidden and makes no contribution to the phenotype. Therefore, recessive alleles can be carried and not expressed by individuals. Such heterozygous individuals are sometimes referred to as carriers. Further genetic studies in other plants and animals have shown that much more complexity exists, but that the fundamental principles of Mendelian genetics still hold true. In the sections to follow, we consider some of the extensions of Mendelism. If Mendel had chosen an experimental system that exhibited these genetic complexities, it’s possible that he would not have understood what his results meant.

Incomplete Dominance

Mendel’s results, that traits are inherited as dominant and recessive pairs, contradicted the view at that time that offspring exhibited a blend of their parents’ traits. However, the heterozygote phenotype occasionally does appear to be intermediate between the two parents. For example, in the snapdragon, Antirrhinum majus (Figure 12.8), a cross between a homozygous parent with white flowers (C^WC^W) and a homozygous parent with red flowers (C^RC^R) will produce offspring with pink flowers (C^RC^W). Note that different genotypic abbreviations are used for Mendelian extensions to distinguish these patterns from simple dominance and recessiveness. This pattern of inheritance is described as incomplete dominance, denoting the expression of two contrasting alleles such that the individual displays an intermediate phenotype. The allele for red flowers is incompletely dominant over the allele for white flowers. However, the results of a heterozygote self-cross can still be predicted, just as with Mendelian dominant and recessive crosses. In this case, the genotypic ratio would be 1 C^RC^R:2 C^RC^W:1 C^WC^W, and the phenotypic ratio would be 1:2:1 for red:pink:white.

Photo is of a snapdragon with a pink flower.

Figure 12.8 These pink flowers of a heterozygote snapdragon result from incomplete dominance. (credit: storebukkebruse/Flickr)

Codominance

A variation on incomplete dominance is codominance, in which both alleles for the same characteristic are simultaneously expressed in the heterozygote. An example of codominance is the MN blood groups of humans. The M and N alleles are expressed in the form of an M or N antigen present on the surface of red blood cells. Homozygotes (L^ML^M and L^NL^N) express either the M or the N allele, and heterozygotes (L^ML^N) express both alleles equally. In a self-cross between heterozygotes expressing a codominant trait, the three possible offspring genotypes are phenotypically distinct. However, the 1:2:1 genotypic ratio characteristic of a Mendelian monohybrid cross still applies.

Multiple Alleles

Mendel implied that only two alleles, one dominant and one recessive, could exist for a given gene. We now know that this is an oversimplification. Although individual humans—and all diploid organisms—can only have two alleles for a given gene, multiple alleles may exist at the population level such that many combinations of two alleles are observed. Note that when many alleles exist for the same gene, the convention is to denote the most common phenotype or genotype among wild animals as the wild type—often abbreviated “+”—this is considered the standard or norm. All other phenotypes or genotypes are considered variants of this standard, meaning that they deviate from the wild type. The variant may be recessive or dominant to the wild-type allele.

An example of multiple alleles is coat color in rabbits (Figure 12.9). Here, four alleles exist for the c gene. The wild-type version, C⁺C⁺, is expressed as brown fur. The chinchilla phenotype, c^chc^ch, is expressed as black-tipped white fur. The Himalayan phenotype, c^hc^h, has black fur on the extremities and white fur elsewhere. Finally, the albino, or colorless phenotype, cc, is expressed as white fur. In cases of multiple alleles, dominance hierarchies can exist. In this case, the wild-type allele is dominant over all the others, chinchilla is incompletely dominant over Himalayan and albino, and Himalayan is dominant over albino. This hierarchy, or allelic series, was revealed by observing the phenotypes of each possible heterozygote offspring.

This illustration shows the four different variants for coat color in rabbits at the c allele. The genotype CC produces the wild type phenotype, which is brown. The genotype c^{ch}c^{ch} produces the chinchilla phenotype, which is black-tipped white fur. The genotype c^{h}c^{h} produces the Himalayan phenotype, which is white on the body and black on the extremities. The genotype cc produces the recessive phenotype, which is white

Figure 12.9 Four different alleles exist for the rabbit coat color (C) gene.

The complete dominance of a wild-type phenotype over all other mutants often occurs as an effect of dosage of a specific gene product, such that the wild-type allele supplies the correct amount of gene product whereas the mutant alleles cannot. For the allelic series in rabbits, the wild-type allele may supply a given dosage of fur pigment, whereas the mutants supply a lesser dosage or none at all. Interestingly, the Himalayan phenotype is the result of an allele that produces a temperature-sensitive gene product that only produces pigment in the cooler extremities of the rabbit’s body.

Alternatively, one mutant allele can be dominant over all other phenotypes, including the wild type. This may occur when the mutant allele somehow interferes with the genetic message so that even a heterozygote with one wild-type allele copy expresses the mutant phenotype. One way in which the mutant allele can interfere is by enhancing the function of the wild-type gene product or changing its distribution in the body. One example of this is the Antennapedia mutation in Drosophila (Figure 12.10). In this case, the mutant allele expands the distribution of the gene product, and as a result, the Antennapedia heterozygote develops legs on its head where its antennae should be.

This photo shows Drosophila that has normal antennae on its head, and a mutant that has legs on its head.

Figure 12.10 As seen in comparing the wild-type Drosophila (left) and the Antennapedia mutant (right), the Antennapedia mutant has legs on its head in place of antennae.

Evolution Connection

Multiple Alleles Confer Drug Resistance in the Malaria Parasite

Malaria is a parasitic disease in humans that is transmitted by infected female mosquitoes, including Anopheles gambiae (Figure 12.11a), and is characterized by cyclic high fevers, chills, flu-like symptoms, and severe anemia. Plasmodium falciparum and P. vivax are the most common causative agents of malaria, and P. falciparum is the most deadly (Figure 12.11b). When promptly and correctly treated, P. falciparum malaria has a mortality rate of 0.1 percent. However, in some parts of the world, the parasite has evolved resistance to commonly used malaria treatments, so the most effective malarial treatments can vary by geographic region.

Photo a shows the Anopheles gambiae mosquito, which carries malaria.

Photo b shows a micrograph of sickle-shaped Plasmodium falciparum, the parasite that causes malaria. The Plasmodium is about 0.75 microns across.

Figure 12.11 The (a) Anopheles gambiae, or African malaria mosquito, acts as a vector in the transmission to humans of the malaria-causing parasite (b) Plasmodium falciparum, here visualized using false-color transmission electron microscopy. (credit a: James D. Gathany; credit b: Ute Frevert; false color by Margaret Shear; scale-bar data from Matt Russell)

In Southeast Asia, Africa, and South America, P. falciparum has developed resistance to the anti-malarial drugs chloroquine, mefloquine, and sulfadoxine-pyrimethamine. P. falciparum, which is haploid during the life stage in which it is infectious to humans, has evolved multiple drug-resistant mutant alleles of the dhps gene. Varying degrees of sulfadoxine resistance are associated with each of these alleles. Being haploid, P. falciparum needs only one drug-resistant allele to express this trait.

In Southeast Asia, different sulfadoxine-resistant alleles of the dhps gene are localized to different geographic regions. This is a common evolutionary phenomenon that occurs because drug-resistant mutants arise in a population and interbreed with other P. falciparum isolates in close proximity. Sulfadoxine-resistant parasites cause considerable human hardship in regions where this drug is widely used as an over-the-counter malaria remedy. As is common with pathogens that multiply to large numbers within an infection cycle, P. falciparum evolves relatively rapidly—over a decade or so—in response to the selective pressure of commonly used anti-malarial drugs. For this reason, scientists must constantly work to develop new drugs or drug combinations to combat the worldwide malaria burden.

According to this passage, why does P. falciparum only need one drug-resistant dhps allele to express the drug resistance trait?

The drug-resistant dhps allele is co-dominant with the wild-type allele.
Only one dhps allele is present during all stages of the P. falciparum life cycle.
Only one dhps allele is present when P. falciparum is infectious.
The drug-resistant dhps allele prevents the wild-type allele from being expressed.

X-Linked Traits

In humans, as well as in many other animals and some plants, the sex of the individual is determined by sex chromosomes. The sex chromosomes are one pair of nonhomologous chromosomes. Until now, we have only considered inheritance patterns among nonsex chromosomes, or autosomes. In addition to 22 homologous pairs of autosomes, human females have a homologous pair of X chromosomes, whereas human males have an XY chromosome pair. Although the Y chromosome contains a small region of similarity to the X chromosome so that they can pair during meiosis, the Y chromosome is much shorter and contains many fewer genes. When a gene being examined is present on the X chromosome, but not on the Y chromosome, it is said to be X-linked.

Eye color in Drosophila was one of the first X-linked traits to be identified. Thomas Hunt Morgan mapped this trait to the X chromosome in 1910. Like humans, Drosophila males have an XY chromosome pair, and females are XX. In flies, the wild-type eye color is red (X^W) and it is dominant to white eye color (X^w) (Figure 12.12). Because of the location of the eye-color gene, reciprocal crosses do not produce the same offspring ratios. Males are said to be hemizygous, because they have only one allele for any X-linked characteristic. Hemizygosity makes the descriptions of dominance and recessiveness irrelevant for XY males. Drosophila males lack a second allele copy on the Y chromosome; that is, their genotype can only be X^WY or X^wY. In contrast, females have two allele copies of this gene and can be X^WX^W, X^WX^w, or X^wX^w.

Photo shows six fruit flies, each with a different eye color.

Figure 12.12 In Drosophila, the gene for eye color is located on the X chromosome. Clockwise from top left are brown, cinnabar, sepia, vermilion, white, and red. Red eye color is wild type and is dominant to white eye color.

In an X-linked cross, the genotypes of F₁ and F₂ offspring depend on whether the recessive trait was expressed by the male or the female in the P₁ generation. With regard to Drosophila eye color, when the P₁ male expresses the white-eye phenotype and the female is homozygous red-eyed, all members of the F₁ generation exhibit red eyes (Figure 12.13). The F₁ females are heterozygous (X^WX^w), and the males are all X^WY, having received their X chromosome from the homozygous dominant P₁ female and their Y chromosome from the P₁ male. A subsequent cross between the X^WX^w female and the X^WY male would produce only red-eyed females (with X^WX^W or X^WX^w genotypes) and both red- and white-eyed males—with X^WY or X^wY genotypes. Now, consider a cross between a homozygous white-eyed female and a male with red eyes. The F₁ generation would exhibit only heterozygous red-eyed females (X^WX^w) and only white-eyed males (X^wY). Half of the F₂ females would be red-eyed (X^WX^w) and half would be white-eyed (X^wX^w). Similarly, half of the F₂ males would be red-eyed (X^WY) and half would be white-eyed (X^wY).

Visual Connection

This illustration shows a Punnett square analysis of fruit fly eye color, which is a sex-linked trait. A red-eyed male fruit fly with the genotype X^{w}Y is crossed with a white-eyed female fruit fly with the genotype X^{w}X^{w}. All of the female offspring acquire a dominant W allele from the father and a recessive w allele from the mother, and are therefore heterozygous dominant with red eye color. All of the male offspring acquire a recessive w allele from the mother and a Y chromosome from the father

Figure 12.13 Punnett square analysis is used to determine the ratio of offspring from a cross between a red-eyed male fruit fly and a white-eyed female fruit fly.

What ratio of offspring would result from a cross between a white-eyed male fruit fly and a and a female fruit fly that is heterozygous for eye color?

Twenty-five percent of the offspring are males and hemizygous dominant with red eyes and 25 percent are male and hemizygous recessive with white eyes. Twenty-five percent are female and heterozygous with red eyes and 25 percent are females and homozygous recessive with white eyes.
Fifty percent of the offspring are male and hemizygous dominant with red eyes and 50 percent are male hemizygous recessive with white eyes. Fifty percent are female and heterozygous with red eyes and 50 percent are female and homozygous recessive with white eyes.
Twenty-five percent of the males are hemizygous dominant with red eyes and 50 percent of the male are hemizygous recessive with white eyes. Twenty-five percent females are heterozygous with red eyes and 50 percent of the females are homozygous with white eyes.
Fifty percent of the males are hemizygous dominant with red eyes and 25 percent of the male are hemizygous recessive with white eyes. Fifty percent females are heterozygous with red eyes and 25 percent of the females are homozygous recessive with white eyes

Discoveries in fruit fly genetics can be applied to human genetics. When a female parent is homozygous for a recessive X-linked trait, she will pass the trait on to 100 percent of her offspring. Her male offspring are, therefore, destined to express the trait, as they will inherit their father's Y chromosome. In humans, the alleles for certain conditions—some forms of color blindness, hemophilia, and muscular dystrophy—are X-linked. Females who are heterozygous for these diseases are said to be carriers and may not exhibit any phenotypic effects. These females will pass the disease to half of their sons and will pass carrier status to half of their daughters; therefore, recessive X-linked traits appear more frequently in males than females.

In some groups of organisms with sex chromosomes, the gender with the non-homologous sex chromosomes is the female rather than the male. This is the case for all birds. In this case, sex-linked traits will be more likely to appear in the female, in which they are hemizygous.

Human Sex-Linked Disorders

Sex-linkage studies in Morgan’s laboratory provided the fundamentals for understanding X-linked recessive disorders in humans, which include red-green color blindness, and Types A and B hemophilia. Because human males need to inherit only one recessive mutant X allele to be affected, X-linked disorders are disproportionately observed in males. Females must inherit recessive X-linked alleles from both of their parents in order to express the trait. When they inherit one recessive X-linked mutant allele and one dominant X-linked wild-type allele, they are carriers of the trait and are typically unaffected. Carrier females can manifest mild forms of the trait due to the inactivation of the dominant allele located on one of the X chromosomes. However, female carriers can contribute the trait to their sons, resulting in the son exhibiting the trait, or they can contribute the recessive allele to their daughters, resulting in the daughters being carriers of the trait (Figure 12.14). Although some Y-linked recessive disorders exist, typically they are associated with infertility in males and are therefore not transmitted to subsequent generations.

A diagram shows an unaffected father with a dominant allele and an unaffected carrier mother with an x-linked recessive allele. Four figures of offspring are shown representing the various resulting genetic combinations: unaffected son, unaffected daughter, affected son, and unaffected carrier daughter.

Figure 12.14 The son of a woman who is a carrier of a recessive X-linked disorder will have a 50 percent chance of being affected. A daughter will not be affected, but she will have a 50 percent chance of being a carrier like her mother.

Link to Learning

Watch this video to learn more about sex-linked traits.

The most common form of hemophilia affects one out of every 5,000 male births worldwide, but the condition is much rarer in females. Explain why this is the case.

Females need two mutated X chromosomes to be hemophilic.
Females need one mutated X chromosome to be hemophilic.
Females do not inherit mutated X chromosomes.
Females need two mutated X chromosomes to not be hemophilic.

Lethality

A large proportion of genes in an individual’s genome are essential for survival. Occasionally, a nonfunctional allele for an essential gene can arise by mutation and be transmitted in a population as long as individuals with this allele also have a wild-type, functional copy. The wild-type allele functions at a capacity sufficient to sustain life and is therefore considered to be dominant over the nonfunctional allele. However, consider two heterozygous parents that have a genotype of wild-type/nonfunctional mutant for a hypothetical essential gene. In one quarter of their offspring, we would expect to observe individuals that are homozygous recessive for the nonfunctional allele. Because the gene is essential, these individuals might fail to develop past fertilization, die in utero, or die later in life, depending on what life stage requires this gene. An inheritance pattern in which an allele is only lethal in the homozygous form and in which the heterozygote may be normal or have some altered non-lethal phenotype is referred to as recessive lethal.

For crosses between heterozygous individuals with a recessive lethal allele that causes death before birth when homozygous, only wild-type homozygotes and heterozygotes would be observed. The genotypic ratio would therefore be 2:1. In other instances, the recessive lethal allele might also exhibit a dominant—but not lethal—phenotype in the heterozygote. For instance, the recessive lethal Curly allele in Drosophila affects wing shape in the heterozygote form but is lethal in the homozygote.

A single copy of the wild-type allele is not always sufficient for normal functioning or even survival. The dominant lethal inheritance pattern is one in which an allele is lethal both in the homozygote and the heterozygote; this allele can only be transmitted if the lethality phenotype occurs after reproductive age. Individuals with mutations that result in dominant lethal alleles fail to survive even in the heterozygote form. Dominant lethal alleles are very rare because, as you might expect, the allele only lasts one generation and is not transmitted. However, just as the recessive lethal allele might not immediately manifest the phenotype of death, dominant lethal alleles also might not be expressed until adulthood. Once the individual reaches reproductive age, the allele may be unknowingly passed on, resulting in a delayed death in both generations. An example of this in humans is Huntington’s disease, in which the nervous system gradually wastes away (Figure 12.15). People who are heterozygous for the dominant Huntington allele (Hh) will inevitably develop the fatal disease. However, the onset of Huntington’s disease may not occur until age 40, at which point the afflicted persons may have already passed the allele to 50 percent of their offspring.

Micrograph shows a neuron with nuclear inclusions characteristic of Huntington’s disease.

Figure 12.15 The neuron in the center of this micrograph (yellow) has nuclear inclusions characteristic of Huntington’s disease—the orange area in the center of the neuron. Huntington’s disease occurs when an abnormal dominant allele for the Huntington gene is present. (credit: Dr. Steven Finkbeiner, Gladstone Institute of Neurological Disease, The Taube-Koret Center for Huntington's Disease Research, and the University of California San Francisco/Wikimedia)

Science Practice Connection for AP® Courses

Activity

This section includes descriptions of genetically inherited human diseases, such as sickle cell anemia, alkaptonuria, hemophilia, color blindness, and Huntington’s disease. One issue surrounding genetic disorders is the right to privacy. Can you think of other examples of ethical, social, or medical issue surrounding human genetic disorders?

Lab Investigation

Investigate inheritance patterns in an organism of choice, such as Wisconsin Fast Plants or Drosophila melanogaster, by performing several genetic crosses and comparing expected and observed phenotypic ratios. Virtual labs exploring Mendelian inheritance patterns are also available online.

Think About It

In pea plants, round peas (R) are dominant to wrinkles peas (r) (Figure 12.5). You do a test cross between a pea plant with wrinkled peas—genotype rr—and a plant of unknown genotype that has round peas—genotype either RR or Rr. You end up with three offspring plants, all which have round peas. Based on the phenotype of the offspring plants, can you deduce the genotype of the round pea parent plant? If the round pea parent plant is heterozygous, calculate the probability that a random sample of three progeny peas will all be round.
Can a human male be a carrier of red-green color blindness? Justify your answer.
In pea plants, violet flowers (V) are dominant to white flowers (v). What are the possible genotypes and phenotypes for a cross between Vv and vv pea plants? Use a Punnett square to show all work.

References

Vinayak, S. et al. (2010, March 26). Origin and evolution of sulfadoxine resistant Plasmodium falciparum. PLoS ,6(3), e1000830. doi: 10.1371/journal.ppat.1000830.

Disclaimer

This section may include links to websites that contain links to articles on unrelated topics. See the preface for more information.

12.2 Characteristics and Traits

Learning Objectives