What you’ll learn to do: Explain complications to the phenotypic expression of genotype, including mutations

Mendel’s experiments with pea plants suggested the following:

1. Two “units” or alleles exist for every gene.
2. Alleles maintain their integrity in each generation (no blending).
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.

Non-Mendelian Inheritance

Incomplete Dominance

Figure 1. These pink flowers of a heterozygote snapdragon result from incomplete dominance. (credit: “storebukkebruse”/Flickr)

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 1), 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.

Codominant Inheritance

Figure 2. Red Roan Horse

A variation on incomplete dominance is codominance, in which both alleles for the same characteristic are simultaneously expressed in the heterozygote.

Codominance can also be seen in human blood types: the AB blood type is a result of both the I^A allele and the I^B allele being codominant. (An A blood type would only have the  I^A allele, and a B blood type would only have  I^B allele.)

The roan coat color in horses is also an example of codominance. A “red” roan results from the mating of a chestnut parent and a white parent (Figure 2). We know this is codominance because individual hairs are either chestnut or they are white, leading to the red roan overall appearance.

Practice Question

So what’s the difference between incomplete dominance and codominant inheritance? While they are very similar, the key difference is this: in incomplete dominance, the two traits are blended together, whereas in codominance, both traits are expressed.

We’ve already discussed incomplete dominance in flowers (Figure 1). What do you think a flower would look like if the red and white phenotypes were codominant instead?

Show Answer

The flower would have both red and white petals, like this Rhododendron:

Codominance is shown in this rhododendron.

Sex-Linked Traits

Figure 3. 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 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 non-homologous chromosomes. Until now, we have only considered inheritance patterns among non-sex 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 3). 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.

Practice Question

Figure 4. 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 and a female that is heterozygous for red eye color?

Show Answer

Half of the female offspring would be heterozygous (X^WX^w) with red eyes, and half would be homozygous recessive (X^wX^w) with white eyes. Half of the male offspring would be hemizygous dominant (X^WY) with red yes, and half would be hemizygous recessive (X^wY) 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.

Non-Mendelian Punnett Squares

This practice activity will help you remember the difference between types of non-Mendelian inheritance and remember just how they work.

Click here for a text-only version of the activity.

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.

ABO blood grouping is an example of multiple alleles.

Multiple Alleles (ABO Blood Types) and Punnett Squares

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 1a), 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 1b). When promptly and correctly treated, P. falciparummalaria 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.

Figure 1. 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.^[1]