Introduction and Goals
This tutorial emphasizes the work of Gregor Mendel, the father of genetics. Mendel was the first scientist to examine, in a quantitative manner, the behavior of traits between generations. By looking at the proportions of different traits in the offspring of a particular genetic cross, he was able to infer the basic tenets of modern genetics. By the conclusion of this tutorial you should have a basic understanding of:
- Mendel and modern genetics
- The distinction between characters and traits
- Meiosis and the segregation of alleles
- The molecular relationship between genotype and phenotype
- The laws of segregation and independent assortment
- Describe the experiments that Mendel did in peas to determine the pattern of inheritance for the characters he studied, using correct terminology
- Explain the phenomenon of complete dominance
- Summarize the relationships between meiosis and both of Mendel’s laws (segregation and independent assortment)
Johann Gregor Mendel (Fig. 1) was born in 1822 and was raised on his parents small farm, in what is now the Czech Republic. After attending high school and the Olmütz Philosophical Institute, Mendel became a friar at an Augustinian monastery in Brno in 1843 at the age of 21. After several years of theological study, Mendel failed his teacher's examination and was sent to the University of Vienna (Austria) for two years of study from 1851-1853.
Figure 1. Johann Gregor Mendel
He returned to the monastery and began his studies of inheritance with pea plants (Pisum) grown in the monastery's garden. He published his work in 1865; however, it went largely unnoticed until its rediscovery in 1900, sixteen years after his death. Mendel's experiments demonstrated many of the basic principles of genetics, and his studies are used to illustrate the fundamental principles of inheritance.
Characters and Traits
Mendel probably chose to work with pea plants because of the many variants that exist in their morphology (physical appearance). The color of the flowers, seeds, and pods can differ between individuals, as can the position of the flower on the stem, the length of the stem, and the shape of the seeds and pods. Pisum provided Mendel with a wide variety of characteristics with which to examine patterns of inheritance. At this point, we need to introduce the terms that Mendel referred to as a character and a trait.
Mendel defined a character as a heritable feature for which variants exist, and a trait as a particular variant for the character. For example, flower color is a character, whereas purple and white are traits. Other characters (and traits) that he studied included: seed color (yellow or green); seed shape (round or wrinkled); pod shape (inflated or restricted); flower position (terminal or axial); and plant height (tall or dwarf).
Mendel's Technique for Crossing Peas
In addition to Pisum's variety of characters and traits with which to study patterns of inheritance, Mendel also probably chose to study peas because their reproduction can be easily manipulated, which gave him strict control over the mating of different individuals. The general process is shown in Figure 2. Peas will often self-fertilize (also termed "selfing"), transferring pollen from the stamens to the carpel on the same flower.
The ease by which peas can be "selfed" played an important role in Mendel's studies. In some cases, Mendel wanted to cross plants with different traits. This required that he prevent selfing by removing the immature stamens before they produced pollen; he then brushed the carpel with pollen from another individual. This enabled him to control the fertilization process, and therefore the parentage of each individual. The pollinated carpel matured into a pod, and the seeds within the pod were planted to give rise to a new generation of adult plants. The mature plants (produced by the seeds) were then scored for these traits, and the process repeated again as desired. This manipulation made it possible for Mendel to keep track of the parents of each individual, and to examine how traits were transmitted through generations
Figure 2. Mendel’s technique for performing a genetic cross between to individual pea plants. (Click image to enlarge)
Mendel tracked heritable characters for three generations. In the first generation, the P generation (parental generation), Mendel crossed two "true-breeding" parents with differing traits for one or more characters. "True-breeding" means that all of the offspring have the same trait as the parent when the offspring are produced by self-pollination. In Figure 3, the individual with white flowers was true-breeding because all of the offspring produced from a self-pollination had white flowers. Similarly, the individual with purple flowers only produced offspring with purple flowers when self-pollinated.
The crossing of two true-breeding parents produced an F1 generation of hybrid individuals that exhibited only the trait found in one of the two parents. The trait that was expressed in the F1 generation was termed a dominant trait. The F1 generation hybrids were then each self-pollinated, producing an F2 generation. Although not present in the F1 generation, the trait exhibited by the one parent reappeared in this generation, at approximately a 3:1 ratio of one parental trait to the other. The trait that reappeared in the F2 generation was termed a recessive trait because it receded in the previous generation. Mendel counted large numbers (hundreds to thousands) of offspring in the F2 generation, allowing him to analyze his results mathematically; using these data he determined the mode and manner of inheritance in this species.
Figure 3. An example of how Mendel tracked heritable characters for three generations. (Click image to enlarge)
The key to understanding Mendelian genetics is to understand what ratios are and how to determine them. Let's do a few exercises to insure that you are familiar with ratios.
In ratios, order means everything. In the example shown above (Fig. 3), the F2 generation had a 3:1 ratio of individuals with purple to white flowers. The same results could be written as a 1:3 ratio of white to purple flowers. Therefore, the order of the traits listed within the ratio are important because the first number in the ratio is related to the first trait listed and the second number in the ratio corresponds to the second trait.
Converting counts to ratios
Some of Mendel's actual data for individual pea plants are listed below. Note that the ratios are obtained by dividing the larger of the two counts by the smaller.
An examination of the ratios listed above shows that they are all approximately a 3:1 ratio, one slightly higher and one slightly lower. The inheritance of traits is governed in some respects by probability (as you will learn in upcoming exercises), therefore, ratios are often rounded to the nearest whole number.
The relationship between ratios and fractions can be confusing. A ratio of 1:3 means that there are four "units" being considered. In other words, 1:3 does not mean 33% have one trait, while 66% have the other. Rather, 1:3 means that 25% (1 unit) have one trait and 75% (3 units) have the other. Observe the punnett square in Figure 4 illustrating the self-pollination of an F1 pea plant for the character of flower color. We’ll learn more about punnett squares in the coming tutorials, just focus on the ratio versus the units.
Figure 4. A Punnett Square showing the predicted result of self-pollination of an F1 individual. (Click image to enlarge)
Estimating Offspring Counts from Ratios
Just as you can calculate ratios from counts of offspring, you can also work backwards and estimate offspring counts from ratios. Let's do an example to demonstrate.
You cross two true-breeding parents, one with purple flowers and one with white flowers, plant the seeds produced, grow the F1 generation an allow the plants to self-pollinate, and then count the number of offspring (the F2 generation) with purple and white flowers. If you counted 1,000 offspring and there was a 3:1 ratio of purple:white flowers, how many offspring would have purple flowers? How many would have white flowers?
Pull out a piece of paper and pencil (and/or your calculator) to see if you can get the right answer before viewing the solution in the next section.
Ratio Problem Solution
n = total number of offspring = 1,000
3:1 ratio = total of 4 "units" (3 + 1 = 4)
3/4 of units have purple flowers, 1/4 have white flowers (Recall, there was a 3:1 ratio of purple:white flowers.)
3/4 = 75%, 1/4 = 25%
75% purple flowers, 25% white flowers
Convert to decimal equivalent: 0.75 purple flowers, 0.25 white flowers
Numbers = n X 0.75 for purple, n X 0.25 for white
purple = 1,000 X 0.75 = 750, white = 1,000 X 0.25 = 250
Estimate = 750 offspring with purple flowers, 250 with white flowers
Work through this animation to reinforce the concept of a Mendelian cross:
Mendel and the Fundamentals of Genetics
Mendel was not the first person to study how traits were passed between generations, however, he was the first to take a careful and quantitative look at the situation. In doing so, he made a number of inferences that continue to have a profound influence on how we think about the transmission of information between generations. He didn't know about DNA, genes, or chromosomes, but his insightful studies laid the groundwork for their discovery.
Mendel quantitatively analyzed how specific traits behaved between generations and concluded that all offspring have two factors for a given character: one was received from the father and one was received from the mother. For a given character (e.g., flower color), one trait was always expressed (i.e., purple was dominant), whereas the other trait might recede ("disappear") between generations (i.e., white was recessive). In other words, recessive traits are only expressed if the two factors are the same (in the homozygous state), whereas a dominant trait will be expressed even if only one factor is present (in the heterozygous state).
Mendel proposed that the discrete units for a given character would segregate away from one another during gamete production (e.g., individuals that were heterozygous with purple flowers could produce gametes with either a white or purple factor, but not both). This is often referred to as the Law of Segregation. Mendel looked at seven different characters and found that each character behaved independent of the other. He concluded that the factors associated with different characters assorted independently (in a random fashion) from one another. This is often referred to as the Law of Independent Assortment. You should be able to relate both the Law of Segregation and the Law of Independent Assortment to the movement of chromosomes during Meiosis I.
It has been about 150 years since Mendel made his observations and inferences. In the years since, geneticists have validated his basic conclusions and we now know they describe the fundamentals of genetics. While we now refer to "factors" as genes, Mendel was the first to predict their presence and behavior between generations. His basic conclusions are as correct today as they were when he first proposed them, and his work spurred the work of thousands of geneticists.
The Molecular Relationship Between Genotype and Phenotype
Figure 5 illustrates the relationship between genotypes and phenotypes, with flower color used as an example. An organism's genotype is its genetic makeup for a particular trait; that is, the alleles it has for a particular gene. The phenotype is the organism's appearance; that is, the trait produced by the alleles the individual has.. How does the genotype for a trait lead to the phenotype? The different alleles at a gene differ in their DNA sequences, thereby producing different enzymes when transcribed into RNA and translated into a protein. These enzymes can have different levels of activity; therefore, the organism's phenotype will differ depending on the enzymes present. The manner in which gene products interact to determine the phenotype is usually complex. The example provided below should help to clarify the relationship between genotype and phenotype.
Figure 5. Genotype versus phenotype. (Click image to enlarge)
In pea plant seed development, water balance plays a pivotal role in determining the phenotype of the wrinkled versus round seeds. Water balance is critical in many physiological and developmental events. Osmosis governs how water partitions between the inside of cells and the outside. (If an osmotically active molecule, like a sugar, is at a higher concentration inside versus outside the cell, then water tends to move into the cell.)
In peas, the character "seed shape" has two traits: the dominant round seed and the recessive wrinkled seed. Pea seeds contain starch, a polymer (chain) of sugar molecules. When the seed is developing, sugar in the seed is converted to starch by a series of enzymes that are encoded by specific genes. The dominant allele R codes for a functional enzyme that effectively participates in starch biosynthesis. The recessive allele r, however, has a defect in its DNA sequence and is nonfunctional.
In individuals with two copies of the recessive allele (rr), sugar accumulates in the developing seed because starch synthesis is incomplete. This accumulation of sugar results in the seeds taking up far more water by osmosis than "normal" seeds. When the seeds dry out at the end of their development, rr seeds lose more water than RR or Rr seeds, resulting in a wrinkled appearance. Heterozygous (Rr) individuals have one functional copy of the starch synthesis gene and resemble the dominant homozygote because they are able to convert sugar to starch within their seeds.
Mendelian Genetics and Human Traits
Traits with simple dominant/recessive expression patterns, where one trait is completely dominant over another, such as those we have discussed so far, are called Mendelian traits. Mendelian traits are found in humans, and include attached versus unattached earlobes (Fig. 6), mid-digital hair, bent thumbs (Fig. 7), and a few other traits. These traits are useful for understanding the basic principles of genetics, but as you will learn in upcoming tutorials, very few traits are actually inherited in this simple manner.
Figure 6. Attached vs. Unattached Earlobes. (Click image to enlarge)
Figure 7. Regular vs Hitchhiker's Thumb. (Click image to enlarge)
Humans have been aware of life cycles for thousands of years. Over the millennia, plant breeders have used variations in crop plants to select for improved varieties without really understanding the fundamentals of genetics. They simply crossed individuals that had the most favorable traits. The science of modern genetics is rooted in the work of Gregor Mendel, who was the first to carefully document the behavior of traits between successive generations. Mendel did not know about chromosomes or alleles, yet his observations predicted their existence. His careful analyses of monohybrid crosses allowed him to deduce that traits may skip a generation, depending on whether or not they are recessive (i.e., heterozygous recessive alleles are not expressed). In other words, he was able to infer the genetic composition (the genotype) by carefully observing the pattern of the observed character traits (the phenotypes) between successive generations.
We now know that the reason for the particular pattern of phenotypic expression in the F2 generation is because of the behavior of chromosomes during meiosis in the F1 generation. Be sure that you understand how the segregation of chromosomes in meiosis provides a mechanism to account for the segregation frequencies observed in the F2 generation.
Keep in mind, Mendel did his work around the time of the American Civil War. For a vivid historical perspective, imagine Mendel tending his garden in Brno (now in the Czech Republic), while across the Atlantic the armies of the North and South were engaged in a devastating war. Since the work of Mendel, we have learned a good deal about genetics. Not only do we understand why Mendel observed the frequencies that he did in the different generations, the molecular events that relate the genotype directly to the phenotype are also understood.
You should have a working knowledge of the following terms:
Case Study for Mendel and Modern Genetics
Dr. Jennifer Arnold and husband Bill Klein both have achondroplasia, a bone-growth disorder that causes dwarfism. They are stars of the reality show "The Little Couple" - Jennifer is a neonatalogist who works at the Texas Children's Hospital (she did her residency at Children's Hospital of Pittsburgh, where most patients older than 4 are taller than she is) and Bill is a businessman. The show features their efforts to build a house that is customized for their size, start a new business, and have a child.
Achondroplasia is caused by an autosomal dominant allele and individuals who inherit two copies of the allele do not survive to birth.
- What is Jennifer's genotype for the gene involved in achondroplasia?
- What is Bill's genotype for the same gene?
- Jennifer and Bill hope to have a child. What is the likelihood that they will give birth to a child with achondroplasia? What is the likelihood that they will give birth to a child without the condition?
Now that you have read this tutorial and worked through the case study, go to ANGEL and complete the tutorial practice problems to test your understanding. Questions? Either send your instructor a message through ANGEL or attend an online office hour (the times are posted on ANGEL).