Beyond Mendel—Part 1

Mendel's Two Laws and the Chromosomal Theory of Inheritance

Law of Segregation

• The two copies of each gene segregate (separate) into different gametes during the formation of eggs and sperm in the parents.
• This explains the 3:1 ratio in the F₂ generation.
• Remember, this is only probabilistic.
  • Mendel's data from the F₂ generation:
    • 705 purple, 224 white
    • 3.15 to 1 ratio
  • The more individuals studied, the closer the ratio comes to the “true” ratio (3:1).
• At the time Mendel did his work, no one knew what chromosomes were, but it turns out that Mendel's Law of Segregation anticipated what chromosomes do in meiosis!

Figure 14.2, page 241, Campbell's Biology, 5th Edition

The Law of Segregation Illustrates What Chromosomes Do in Meiosis

• There are parallels between what Mendel's elements of heredity do and what chromosomes do during meiosis.
• Scientists noticed these after Mendel's famous paper was rediscovered in 1900.
• These led to the Chromosomal Theory of Inheritance.
  • Chromosomes carry Mendel's elements of heredity.
  • Separation of homologous chromosomes in meiosis is responsible for the segregation of alleles in Mendel's experiments.

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Law of Independent Assortment

• Alleles of different genes assort independently during gamete formation.
• This explains the 9:3:3:1 ratio in the F₂ generation of a dihybrid cross.
• Mendel's data from the F₂ generation doesn't give a perfect ratio, but it is close enough since the process is the result of probabilities.
  • 315:108:101:32 ≈ 9.84:3.38:3.16:1

The Law of Independent Assortment Illustrates What Chromosomes Do in Meiosis

• The independent assortment of homologous chromosomes during meiosis explains the independent assortment of Mendel's units of heredity.

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Chromosomal Theory of Inheritance

• The chromosomal theory states that Mendel's units of heredity are located at specific places (loci) on chromosomes, and it is the chromosomes that undergo segregation and independent assortment.
• Once this was accepted, around 1903, Mendel's laws of heredity, which were based on mathematical probabilities (and therefore rather abstract), were given a physical basis.
• As a result, the science of genetics exploded.
  • 50 years later the molecule of heredity was discovered: DNA.
  • 75 years later genes were taken from one organism and spliced into another.

Reductionism: A Strategy that Works

• Reductionism defined
  • An attempt or tendency to explain a complex set of facts, entities, phenomena, or structures by another, simpler set.
  • “For the last 400 years science has advanced by reductionism. The idea is that you could understand the world, all of nature, by examining smaller and smaller pieces of it. When assembled, the small pieces would explain the whole.” (John Holland)
• Galileo, Newton, and Mendel took a reductionist approach to understanding the physical and biological world.
  • They broke nature down into little pieces that were simple and could be studied and understood.
  • Once they understood the simple laws upon which the universe is constructed, they could build up a more complex understanding.
  • This allowed major breakthroughs in understanding nature.

All Models are Partial Truths

• While the reductionist approach has given us a foothold in understanding nature, in all cases the models of how the universe works are imperfect.
• Gregor Mendel's amazing discovery of the Laws of Inheritance was an intellectual breakthrough of the first order—one of the greatest discoveries in the history of science.
• However, Mendel ignored what he didn't understand and radically simplified things.

Mendel's Model

1. Peas have two versions, or alleles, of each gene. This also turns out to be true for many other organisms.
2. Alleles do not blend together. The hereditary determinants maintain their integrity from generation to generation. They do not blend together, and they do not acquire characteristics in response to actions by an individual (like a giraffe stretching its neck).
3. Each gamete contains one allele of each gene. Pairs of alleles segregate during the formation of gametes.
4. Males and females contribute equally to the genotype of their offspring. When gametes fuse, offspring acquire a total of two alleles for each gene—one from each parent.
5. Some alleles are dominant to others. When a dominant and recessive allele for the same gene are found in the same individual, that individual exhibits the dominant phenotype.

Mendel's First Partial Truth: Complete Dominance

• Traits are not always either dominant or recessive.
• What Mendel described in his famous pea experiments is now know as complete dominance.
  • One allele is completely dominant over another allele, which is termed recessive.
• Example: if we examine the trait for plant height we see that it is controlled by two alleles.
  • T represents the tall allele and is dominant.
  • t represents the short allele and is recessive.
  • Both the TT and Tt genotypes correspond to the tall phenotype.
  • Reason: the T allele shows complete dominance over t.

Incomplete Dominance

• In incomplete dominance, one allele of a pair isn't fully dominant over its partner.
  • It looks like blending is happening.
  • The F₁ generation looks intermediate between the two parents.
• Example: In snapdragons, the red flower allele (C^R) is incompletely dominant to the white flower allele (C^W).
  • The offspring of these two is halfway between them in color—it is pink!
  • That is, the heterozygous phenotype (C^RC^W) is somewhere in between the two homozygous phenotypes (C^RC^R and C^WC^W)
  • How does this work?
    • The C^R allele codes for a red flower pigment; the C^W does not code for a pigment.
    • The C^RC^R individual gets the full amount pigment, and is red.
    • The C^RC^W gets only half the amount of pigment, and looks pink.
    • The C^WC^W gets no pigment and looks white.

Figure 14.9, page 248, Campbell's Biology, 5th Edition

Codominance

• In codominance, both alleles are expressed in the heterozygous offspring.
• Example: ABO blood groups
  • Four phenotypes exist for this character: a person may be A, B, AB, or O.
  • These letters refer to two carbohydrates, substance A and substance B, which may be found on the surface of red blood cells.
  • A person's blood cells may be coated with one substance or the other (type A or type B), with both (type AB), or with neither (type O).

Via Domenic Denicola's mad Photoshop skills.

Implications in Blood Transfusions

• Matching compatible blood groups is critical for blood transfusions.
• If the donor's blood has a factor that is foreign to the recipient (A or B carbohydrates attached to the surface of the red blood cells),
  • Antibodies produced by the recipient bind to the foreign molecules.
  • The donated blood cells agglutinate (clump together).
  • This is not a good thing, and can kill the patient.

Three Different Alleles Account for Four Different Blood Types

• The four blood groups result from various combinations of three different alleles of one gene, symbolized by:
  • I^A for the A carbohydrate.
  • I^B for the B carbohydrate.
  • i, giving rise to neither the A carbohydrate nor the B carbohydrate.
• The I^A and I^B alleles are dominant to the i allele
• Six genotypes are possible, corresponding to four phenotypes:
  • I^AI^A and I^Ai individuals have type A blood.
  • I^BI^B and I^Bi individuals have type B blood.
  • I^AI^B individuals produce both carbohydrates and have type AB blood.
  • ii individuals produce neither carbohydrate and have type O blood.

Blood Type	Genotype	Carbohydrates on Cell Surface	Antibodies	Acceptable Blood Types
A	IAIA or IAi		Anti-B	A and O
B	IBIB or IBi		Anti-A	B and O
AB	IAIB		None	Any (universal recipient)
O	ii		Anti-A and anti-B	O (universal donor)

Summary of Dominance Relationships

• Dominance is on a continuum: complete dominance … incomplete dominance … codominance
• These different dominance patterns reflect the mechanisms by which specific alleles are expressed in phenotypes.
  • Alleles do not subdue one another (or “dominate”) at the level of the DNA.
  • Dominance patterns have no relationship to allele frequency in the population: that is governed by natural selection.

Other Exceptions to Simple Mendelian Genetics

Pleiotropy

• One gene has multiple effects.
• Classic example: sickle-cell anemia
  • A change in a single gene causes a change in hemoglobin (a protein found in red blood cells).
  • The abnormal hemoglobin causes the red blood cells to deform (hence the term “sickle cell”).
  • This deformation of the cells causes the red blood cells to get stuck in the capillaries.
  • The blocking of the capillaries results in a variety of different diseases.
  • From one bad gene stem many effects, as shown below.

Figure 14.15, page 254, Campbell's Biology, 5th Edition

Epistasis

• One gene influences the effect of another gene.
• In other words, a gene at one locus alters the phenotypic expression of a gene at a second locus.
• Example: coat color in mice
  • The allele for a black coat (B) is dominant over the allele for a brown coat (b).
  • A second gene (with alleles C and c) determines whether or not pigment will be deposited in the hair.
  • A mouse that is homozygous recessive (cc) for this second gene will be albino (no pigment will be deposited).
  • One gene (alleles C and c) controls the expression of another (alleles B and b).

Figure 14.11, page 250, Campbell's Biology, 5th Edition