Posted October 19, 2000
Lecture date: Friday, October 20, 2000

Lecture 20, MCDB 2150, Fall 2000

Mendel: Monohybrid crosses, genetic segregation, dominance

Textbook assignment: Chapter 12, pages 347-358. You may also find it useful to review Chapter 1, Pages 3-17, at this time.

Major Topics

Overview: Gregor Johann Mendel originally presented the results of his studies on plant hybridization as a series of two lectures to the Natural History Society of Brünn (now Brno in the Czech Republic) on February 8 and March 8, 1865. They were published the following year in the journal of the society, with 115 copies known to have been distributed. For details, see the Notes section of the Mendel Web . This lecture examines the first three principles of inheritance that were postulated by Mendel, based on his experimental observations.

  1. Unit factors of inheritance occur in pairs;
  2. When unlike unit factors affecting the same character are present in an individual one will be dominant and the other recessive.
  3. Unit factors segregate randomly during formation of gametes
. As we examine this work, it is important to remember that it was done before there was any clear understanding of the behavior of chromosomes in meiosis or of the haploid/diploid nature of sexual life cycles. Thus, Mendel derived the laws of inheritance strictly from his own observations.

Dominant and recessive alleles; genotype and phenotype: The genotype of the individual that develops from the zygote is the sum of all of the genes inherited from both parents, including those that are not overtly expressed. Alleles are alternative or forms of the same gene. If there is no difference in the alleles received from the two parents at a particular genetic locus, the individual is said to be homozygous for that gene. If a different allele is received from each parent, the individual carries two different forms of the gene and is heterozygous. The phenotype (overt display of genetic properties) of a heterozygous individual is determined by the dominance relationship between the two alleles. If one allele is completely dominant over the other, the phenotype of the heterozygote will be the same as the dominant homozygous phenotype, with the alternative phenotype occurring only in individuals who are homozygous for the recessive allele.

Alternative dominance relationships: Note that there are also genes that exhibit codominance (such as M, N and MN blood types) and partial dominance (such as pink flowers in a heterozygote between red and white). These and other modifications of Mendel's ratios will be discussed in the lectures for chapter 13 of the textbook.

Properties of good model systems for studying inheritance: One of the critical requirements for doing genetic studies is to have a good model system. All of the following are considered desirable in a genetic model system (see Chapter 1, Section 3, Pages 7 - 9, for a discussion of model systems):

  1. Phenotypic markers that can be detected readily.
  2. A reasonably short generation time so that many rounds of experiments based on the results of previous experiments can be performed.
  3. Small size and ease of handling of large numbers of organisms.
  4. Ability to perform controlled matings.
  5. A pattern of inheritance that is relevant to the system it is a model for.
Mendel's model system, the garden pea: The model system that Mendel used was the garden pea, pisum sativum. The properties of that system are discussed below in relationship to the five desirable properties listed above.
  1. Mendel employed seven different phenotypic markers, all of which exhibited clear patterns of dominance and recessiveness (Figure 1.10, Figure 12.2 and Table 12.1):

  2. With only one generation per growing season, Mendel's peas were very slow by modern standards, but over a period of several years, they yielded adequate data. In addition, the fact that several of the markers could be scored using the seed as progeny without the need to grow up another full generation of plants hastened the process.

  3. Pea plants are relatively large experimental organisms, but Mendel was able to work with a sufficient number in a reasonable sized garden.

  4. Peas are capable of being cross pollinated both artificially and by insects. However, the lower petals of the flowers remain closed over the anthers and stigma (figures 12.2 and 12.3), such that fertilization is achieved primarily by self-pollination. By removing anthers before they produced mature pollen, Mendel was able to prevent self-fertilization and thus to perform controlled crosses by artificial fertilization (Figure 12.3). Self-pollination increases the homozygosity of populations, as we shall see in the unit on population genetics near the end of the semester. This, together with a long history of cultivation of peas as a garden crop, made it relatively easy for Mendel to obtain seed for plants with diverse phenotypes and to isolate the true breeding (homozygous) parental populations that were needed for his studies.

  5. The pattern of inheritance exhibited by the garden pea is an accurate model for studying the genetics of domestic animals and of humans.

Experimental results: The results of crosses for each of the seven markers that were studied by Mendel are given in Table 12.1. of the textbook. As an example, a cross of true breeding parents (called the P1 generation) with round and wrinkled seeds yielded first generation hybrids (designated F1 for first filial generation) whose seeds were all round (round is dominant over wrinkled in a heterozygote).

Note that the seeds produced by the parental plants are embryonic forms of the F1 generation, even though they have not yet grown to maturity.

When plants grown from these round heterozygous F1 seeds were allowed to self-fertilize, they yielded an F2 (second filial) generation that consisted of 5,474 round seeds and 1,850 wrinkled seeds, essentially a 3:1 ratio. Similar results were obtained in single trait (monohybrid) crosses involving each of the other six markers (Table 12.1).

Mendel's first three principles of inheritance:

  1. Particulate inheritance: Mendel was able to demonstrate that inheritance of individual markers occured in an "either-or" mode, as opposed to the "blending" theory of inheritance that was popular at the time. Thus, seeds were smooth or wrinkled, stems were tall or short, flowers were violet or white, etc., in F1 hybrids of true-breeding parents, rather than intermediate between the parental extremes. (Note that this is not always valid for all genetic markers, as we shall see in future lectures)
  2. Dominance and recessiveness: When two unlike unit factors (alleles) are present in a heterozygote, the phenotype of one of them will dominate. The recessive allele will be present, but not expressed. Different genotypes (homozygous dominant and heterozygous dominant/recessive) will exhibit the same phenotype. Thus, for example, a cross between true breeding parents with round and wrinkled seeds always yielded round seeds in the F1 generation.
  3. Segregation of unit factors of inheritance into gametes: Half of the gametes produced by a heterozygote contain the dominant unit factor (allele) and the other half contain the recessive unit factor (allele). Homozygous progeny produced from the fusion of two gametes that both contain the recessive unit factors (alleles) will exhnbit the recessive phenotype. This verifies that the recessive unit factors (alleles) are present in the heterozygous plants even though they are not expressed pheonotypically.

Molecular basis for dominance and recessiveness: As we proceed through the semester, we will see a variety of ways in which dominance and recessiveness can be generated. However, by far the most frequent mechanism is a loss of function mutation in the recessive allele (Figures 1.19 and 12.6). In the simplest case, the homozygous recessive individual (aa) makes no functional gene product (enzyme, regulatory protein, structural protein, etc.). The heterozygote has one good allele and one mutant allele (Aa). In many cases, one good allele codes for enough of the gene product so that the heterozygote is phenotypically indistinguishable from homozygous dominant (AA). (However, it should be noted that sensitive biochemical assays can often detect a reduced level of enzymatic activity in phenotypically normal individuals who have only one functional allele coding for the enzyme under study).

Wrinkled seeds: Boxed example 12.2 describes studies showing that Mendel's wrinkled seed phenotype resulted from an insertion mutation (presumably of a transposable element) into the coding sequence for a starch-branching enzyme. Without fully branched starch, the seeds retain less water and become wrinkled. One functional allele coding for the enzyme is enough to cause the seeds to be round.

Chromosomal basis for Mendel's observations: As described in the previous lecture, a diploid organism has two complete sets of all chromosomes (with the exception of sex chromosomes, which will be discussed separately in a later lecture). Meiosis results in the formation of haploid gametes that contain only one complete set of chromosomes. When a haploid sperm cell or pollen grain fertilizes a haploid ovum or ovule, the resultant zygote again has a diploid genome, with one complete set of chromosomes (and the genes they carry) inherited from the male parent and a second complete set inherited from the female parent. The pattern of inheritance of unlinked genes (those carried on different chromosomes) is the same as the distribution of the chromosomes that carry them (see diagrams on page 356).

Designations for dominant and recessive alleles: Mendel introduced the practice of using an upper case (capital) letter to describe a dominant allele and a lower case letter to describe a recessive allele. He did not give names to the individual genetic loci he worked with, but instead always used A for dominant and a for recessive. In experiments involving additional loci, he employed the symbols B and b, C and c, etc. However these letters referred only to the second and third genetic loci involved in a particular experiment, and were not permanently associated with specific loci.

Selection of names for genes: The practice of using a capital letter for dominant allele and a lower case letter for recessive is quite universal, there is no clear consensus as to whether a gene should be named for the normal function that it supports or the recessive phenotype that results from its loss of function. In classical genetics, this was further complicated by lack of knowledge about anything other than the phenotypes associated with the dominant and recessive traits.

Names based on dominant phenotypes: In our textbook (and many others), you will find true-breeding round peas designated as RR and true-breeding wrinkled designated as rr, with the heterozygote called Rr. In other systems where the biochemical function of the genetic locus was at least partially understood when names were being assigned, the name is also usually based on the dominant phenotype or the normal biochemical function of the gene product. These notes will follow the example of our current textbook and use nomenclature based on the dominant form to describe experiments done with peas. However, you need to be aware that alternative designations are also used.

Names based on recessive phenotypes: In many widely studied model systems, such as Drosophila, recessive alleles occur primarily as loss-of-function mutations derived from "wild type" strains by treatment with radiation or other mutagens. In such cases, the genetic locus is usually named for the recessive mutant phenotype, as we saw earlier for vermillion and cinnebar eye colors in Drosophila, both of which were due to loss of ability to synthesize brown pigment (Pages 166-170). Some textbooks (including Klug and Cummings, Concepts of Genetics, 5th Edition, a previous text for this course that is on reserve in Norlin) use the recessive phenotype as the basis for naming genes in peas. In such cases, capital letters are still used for dominant and lower case for recessive. Thus, you will sometimes see round peas described as WW (or Ww) and wrinkled peas designated ww.

Modern symbols for genetic loci in peas: It should be noted that most of the symbols commonly used in elementary genetics textbooks for the genetic markers employed by Mendel do not match the terminology used in modern genetic analysis of peas. Figure 12.13 shows current terminology for the genes that our authors believe that Mendel studies applied to a chromosomal map of peas (see "Absence of linkage" near the end of these notes for a further discussion of which loci Mendel actually studied).

Diverse systems of gene nomenclature: As we will see in future lectures, the conventions used for naming genetic loci and describing alternative alleles differ very substantially from one model system to another (briefly summarized on textbook pages 384-385). It is therefore important not to assume that patterns you have learned for one model system will cary over to others.

Phenotypic ratio: When two heterozygous Aa parents are crossed, each produces A and a gametes in equal numbers. Fertilization can give rise to four possible types of progeny, AA, Aa, aA, and aa. Note that the two heterozygous progeny are functionally equivalent. It makes no difference whether the dominant A allele is contributed by the pollen grain or the ovule. However, because two different fertilization events can give rise to heterozygous progeny, their total number (Aa plus aA) is twice that of either of the classes of homozygous progeny (AA or aa). . Thus, when two heterozygotes are crossed, the ratio of progeny with the dominant phenotype (AA, Aa, aA) to progeny with the recessive phenotype (aa) is 3:1.

Punnett square: The Punnett square, named after its inventor, Reginald C. Punnett, is a convenient way to display all possible genotypes of the progeny of a cross. A Punnett square is set up as a table with borders. All possible gametes that can be produced by one parent are displayed across the top and all possible gametes that can be produced by the other parent are displayed down the left side. The remaining squares are filled in with the genotypes that are generated by fusing the gamete at the top of the the column with the gamete at the left end of the row (Figure 12.7 in the textbook).

Test cross: A back cross is a cross of a hybrid with one of its true-breeding parental strains. For an F1 heterozygote, a test cross is a back cross with its recessive parental strain. However, the term test cross is also used more broadly to describe a cross at any generational level in which the second parent is homozygous recessive. A test cross is a powerful tool for genotypic analysis because the genotype of the individual that is test crossed can be read directly from the phenotypes of the progeny, with no need for further crosses. This is a technique that we will encounter repeatedly. Be sure that you understand and remember it.

Critical features of Mendel's research on monohybrid crosses

  1. He carefully verified the true-breeding (homozygous) nature of parental stocks.
  2. He used F1 hybrids to disprove blending; one parental phenotype was dominant.
  3. He used F2 hybrids to verify that recessive alleles were retained in F1 hybrids.
  4. He proposed a model for inheritance, based on observed data and successfully predicted results of additional experiments based on the model:

We will see in future lectures that there are many exceptions to strictly Mendelian genetics. However, by rigorous applications of the principles described above, Mendel was able identify the basic principles of inheritance in diploid organisms many years before the mechanisms that are involved began to be understood.