Revised October 18, 1999 This lecture is based on 1998 Lecture 3.

Lecture 21, MCDB 2150, Fall 1999

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.

1. He employed seven different phenotypic markers, all of which showed a clear pattern of dominance and recessiveness relationship (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 a relatively large experimental organism, but Mendel was able to work with a sufficient number in a reasonable sized garden.

4. Although they are capable of being cross pollinated both artificially and by insects, peas multiply 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 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. Homozygous progeny produced from the fusion of two gametes that both contain the recessive unit factors (alleles) will exhnbit the recessive phenotype.

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 (figure 12.6). In the simplest case, the homozygous recessive individual (aa) makes no functional enzyme. The heterozygote has one good allele and one mutant allele (Aa). In many cases, one good allele codes for enough of the enzyme so that the heterozygote is phenotypically indistinguishable from homozygous dominant (AA). (However, it should be noted that sensitive biochemical assays can often detect twice as much enzymatic activity in the latter). 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 become wrinkled.

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 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 poage 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: Although the practice of using a capital letter for dominant 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 loss of funciton. In classical genetics, this was further complicated by lack of knowledge about anything other than the phenotypes associated with the dominant and recessive traits. 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. However, in many systems, 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, used last year in this course) use the recessive phenotype as the basis for gene designations in peas. In such cases, capital letters are still used for dominant and lower case for recessive. Thus, you will sometimes see round peas designated WW (or Ww) and wrinkled peas designated ww. However, these notes will follow the example of our current textbook and use nomenclature based on the dominant form.

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 12.3 shows current terminology applied to a chromosomal map of peas.

Drosophila: Note that the symbols used to describe mutations in Drosophila, which are described at the end of this lecture, are based on mutant phenotypes, with capital letters used for dominant mutations and lower case for recessive mutations.

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 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 predicted results of additional experiments based on the model

Absense of linkage: Mendel's original studies dealt only with genes in which there was complete dominance of one allele over the other. In addition, the genes he studied were all on separate chromosomes or else so far separated from one another on the same chromosomes so that they did not exhibit any detectable linkage to one another (Figure 12.13). One possible exception may be the locus with alleles that determine full versus constricted pods. Our textbook associates those traits with the P locus on Chromosome VI. However, last year's text (Klug and Cummings, Concepts of Genetics, 5th Edition -- Norlin Reserve) and the Mendel Web Glossary assign those traits to the V locus on chromosome IV, which is located close enough to the stem length locus Le (tall vs. dwarf) so that they should exhibit linkage. Mendel never reported experiments designed to demonstrate independent assortment of those two characteristics. This, together with the uncertainty about which locus he worked with makes it uncertain as to whether he never observed linkage or rejected it as a bad experiment that did not match the rest of his data.

Symbols for alleles in Drosophila: Because we will be using the fruit fly, Drosophila melanogaster, as our experimental organism in the laboratory simulations we do with the Virtual FlyLab, it is desirable to introduce the symbols used for dominant and recessive alleles in Drosophila at this time. Genetic studies in Drosophila begin with a true-breeding laboratory strain that is referred to as "wild type". The genetic markers that are studied cause detectable phenotypic differences from the wild type, and may be either recessive or dominant relative to the wild-type phenotype. A recessive allele is designated with a lower case letter or small group of letters, and a dominant allele is designated with a capital letter, which may be followed by one or more lower case letters. Thus, a recessive allele causing a black body is designated b, and a dominant gene causing roughened eyes is designated R. The corresponding wild type genes are designated by a plus sign (+), either standing alone, or as a superscript to the symbol for the mutant allele.

Genotype is designated by the two alleles that are present, separated by a slash (/). Thus +/b or b+/b indicates a heterozygote with one wild type allele and one recessive black body allele, which would result in a wild-type pheonotype. Similarly +/R would indicate a heterozygote with one copy of the dominant R allele, which would exhibit a rough-eyed phenotype. The homozygous wild type genotype is indicated by +/+. The symbols used for alleles in Drosophila are described on pages 384-385 of the textbook and illustrated in Figure 15.3 on page 448.

Please note that the Virtual FlyLab uses non-standard symbols that have deliberately been made ambiguous so you will not know whether specific mutations are dominant or recessive prior to doing experiments with them.