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 (CWCW) and a homozygous parent with red flowers (CRCR) will produce offspring with pink flowers (CRCW). 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 CRCR:2 CRCW:1 CWCW, and the phenotypic ratio would be 1:2:1 for red:pink:white.
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 (LMLM and LNLN) express either the M or the N allele, and heterozygotes (LMLN) 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, cchcch, is expressed as black-tipped white fur. The Himalayan phenotype, chch, 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.
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.
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.
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 (XW) and it is dominant to white eye color (Xw) (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 XWY or XwY. In contrast, females have two allele copies of this gene and can be XWXW, XWXw, or XwXw.
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 (XWXw), and the males are all XWY, having received their X chromosome from the homozygous dominant P1 female and their Y chromosome from the P1 male. A subsequent cross between the XWXw female and the XWY male would produce only red-eyed females (with XWXW or XWXw genotypes) and both red- and white-eyed males—with XWY or XwY 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 (XWXw) and only white-eyed males (XwY). Half of the F2 females would be red-eyed (XWXw) and half would be white-eyed (XwXw). Similarly, half of the F2 males would be red-eyed (XWY) and half would be white-eyed (XwY).
Visual Connection
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.
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.