Mendel and the Gene Idea

Early theories of Inheritance

I. EARLY THEORIES OF INHERITANCE

Many theories of inheritance have been proposed, and some data back as far as ancient Greece.

Aristotle proposed the theory of pangenesis which held that particles (called pangenes) from all parts of the body come together to form the eggs and sperm.
1. Changes that occurred in the various body parts during an organism's life could be passed on to the next generation.
2. Pangenesis was accepted by many (Lamarck and Darwin) and was the prevailing theory into the nineteenth century.
3. Pangesesis is incorrect because reproductive cells are not composed of contributions from body cells and changes in body cells do not influence egg and sperm cells.
In the seventeenth century, Aton van Leeuwenhoek "observed " the homunculus, a miniature human being, in human sperm cells. He and his followers (spermists) believed that:
1. The mother serves only as an incubator for the homunculus.
2. All characteristics are inherited from the father.
Also during the seventeenth century, Regnier de Graaf and his followers (ovists) proposed that:
1. The egg contains an entire human in miniature and that semen only stimulates its growth.
2. All characteristics are thus inherited from the mother. deGraff was the first person to describe the ovarian follicle in which human egg cells are produced.
Based upon their observations with ornamental plant breeding, scientists in the nineteenth century realized that both parents contribute to the characteristics of offspring. The "blending" theory then became the favored explanation of inheritance. According to this theory:
1. Hereditary materials from male and female parents mix to form the offspring, and once blended, the hereditary material is inseparable.
2. Since the hereditary material is inseparable, the population should reach a uniform appearance after many generations.
This theory was inconsistent with the observations that:
1. Populations do not reach a uniform appearance.
2. Some traits are absent in one generation and present in the next.
Modern genetics began in the 1860's with the experiments of an Augustinian monk named Gregor Mendel who discovered the fundamental principles of inheritance.

Mendel and the Gene Idea

Mendel's Model of Inheritance

II. MENDEL'S MODEL OF INHERITANCE

Mendel
pea life cycle
pea cross fertilisation
Mendel pea characters
Mendel's first experiment
Mendel's results
Mendel's explanation
Backcross
Testcross
Independent assortment
linked-genes
flowers
geno- vs phenotypes
Chromosomes. Haploid vs diploid
sex chromosome
Drosophila sex genes
Haamophilia genes
ABO blood system
ABO blood test
Cartoon!

Mendel's work demonstrated that parents pass on to their offspring discrete heritable factors (genes) which retain their individuality generation after generation (in contrast to the blending theory).
Although Mendel's work is the basis of modern genetics, it did not influence the scientific community until many years after his death.
Mendel's Methods
1. Unlike most nineteenth century biologists, Mendel adopted a quantitative approach to his experimentation.
2. His experimental organisms were garden peas which proved to have many advantages over other possible organisms:
  1. They were easy to grow.
  2. They were available in many easily distinguishable varieties.
  3. Strict control over mating was possible (small bags over flowers prevented cross-pollination; immature stamens could be removed to prevent self-pollination) to insure the parentage of new seeds.
3. Mendel not only applied quantitative methods but also chose traits which differed in a relatively clear-cut manner.
  1. Mendel chose seven characteristics, each of which occurred in two forms: seed shape (round or wrinkled), seed color (yellow or green), seed coat color (gray or white), pod shape (inflated or constricted), pod color (green or yellow) flower position (axial or terminal), stem length (tall or dwarf).
4. Mendel worked with his plants until he obtained true-breeding plants (varieties which always produced offspring with the same traits as the parents when the parents were self-fertilizing). He hybridized (cross-pollinated) these true-breeding varieties in experimental crosses.
  1. Parental plants of such a cross are called the P generation.
  2. The hybrid offspring of the P generation are the F1 generation (first filial).
  3. Mendel also allowed F1 generation plants to self-pollinate to produce the next generation, the F2 generation.
5. Mendel observed the transmission of selected traits for several generations and arrived at two principles of heredity which are now known as the law of segregation and the law of independent assortment.
Mendel's Law of Segregation
1. When Mendel crossed true-breeding plants exhibiting different forms of a trait, green-pod and yellow-pod color, he bound that the traits did not blend, but that the F1 progeny (offspring) produced only green-colored pods.
  1. Mendel hypothesized that if the heritable factor for yellow pods had been lost, then the F1 plants should only be capable of producing green-pod progeny.
  2. Mendel allowed the F1 plants to self-pollinate to produce the next generation. In this F2 generation, there were 428 plants with green pods and 152 plants with yellow pods which gives a 3:1 ratio of green to yellow.
  3. From these types of experiments and observations, Mendel concluded that the heritable factor for yellow pods was not lost in the F1 plants, but was masked by the presence of the green-pod factor.
  4. We now call these heritable factors genes.
2. Mendel formulated his hypothesis of inheritance which can be divided into four parts:
  1. There are alternative forms for genes, the units that determine inheritable characteristics:
    1. The gene for pod color existed in two alternative forms, one for green and one for yellow.
    2. Alternative forms of a gene are now called alleles.
  2. For each inherited characteristic, an organism has two alleles, one inherited from each parent.
    1. Mendel's experiment included on parental variety which had a pair of alleles for green pod color and one which had a pair of alleles for yellow pod color.
    2. The F1 hybrids inherited from the parental plants one allele for green pod color and one allele for yellow pod color.
  3. A sperm or egg carries only one allele for each inherited characteristic, because allele pairs separate (segregate) from each other during the production of gametes. At fertilization, the sperm and egg unite with both contributing their alleles. This restores the gene to the paired condition.
    1. In Mendel's experiment, each gamete of a parental plant carried one allele for pod color, specifying either green or yellow.
    2. Cross-pollination to produce the F1 resulted in the combination found in this generation.
  4. When the two alleles of a pair are different, one is fully expressed and the other is completely masked. These are called the dominant allele and recessive allele, respectively.
    1. Mendel's F1 hybrid had green pods, which was recessive.
3. Mendel's hypothesis explains the 3:1 ratio of progeny plant types he observed in the F2 generation.
  1. It predicts that the F1 hybrids (Gg) will produce two classes of gametes when the pairs separate during gamete formation.
  2. Half will receive a green-pod (G) allele and the other half the yellow-pod allele (g).
  3. During self-pollination, these two classes of alleles unite in a random manner.
  4. Eggs containing green-pod alleles have equal chances of being fertilized by sperm carrying preen-pod alleles or sperm carrying yellow-pod alleles.
  5. Since the same is true for eggs containing yellow-pod alleles, there are four equally likely combinations of sperm and eggs.
4. The combinations resulting from a genetic cross may be predicted by using a device called a Punnett Square.
  
  P generation: GG x gg
  
  green yellow
  
  F₁ generation: Gg x Gg
  
  green green
  
  F₂ generation:
5. The F2 progeny would include:
  1. One-fourth of the plants with two alleles for green pod color.
  2. One-half of the plants with one allele for green pods and one allele for yellow pods. Since the green pod allele is dominant, these plants have green pods.
  3. One-fourth of the plants with two alleles for yellow pod color which will have yellow pods since no dominant allele is present.
6. The pattern of inheritance for all seven of the characteristics studied by Mendel was the same: one parental trait disappeared in the F1 generation and reappeared in one-fourth of the F2 generation.
7. The mechanisms producing this pattern of inheritance is stated by Mendel's Law of Segregation: allele pairs segregate (separate) during gamete formation, and the paired condition is restored by the random fusion of gametes at fertilization.
  1. Research since Mendel's time has established that the law of segregation applies to all sexually reproducing organisms.
8. Some Useful Genetic Vocabulary:
  1. Dominant alleles are indicated by a capital letter: G=green pod color.
  2. Recessive alleles are indicated by a lowercase letter: g=yellow pod color.
  3. An organism with a pair of identical alleles for a characteristic (GG or gg) is homozygous and all gametes carry that allele.
    1. Homozygotes are true-breeding.
  4. An organism that has two different alleles for a trait (Gg) is said to be heterozygous and one- half of the gametes carry one allele (G) with the other half carrying the other allele (g).
    1. Heterozygotes are not true-breeding.
  5. Phenotype = An organism's expressed traits (green or yellow). In Mendel's experiment, the F2 generation had a 3:1 phenotypic ratio of plants with green pods to plants with yellow pods. Genotype = An organism's genetic makeup (GG, Gg or gg). The genotypic ratio of the F2 generation was 1:2:1 (1GG:2Gg:1gg).
The Testcross
1. Because some alleles are dominant over others, the phenotype of an organism does not always reflect its genotype.
  1. A recessive phenotype (yellow) is only expressed with the organism is homozygous recessive (gg).
  2. A pea plant with green pods may be either homozygous dominant (GG) or heterozygous (Gg).
  3. To determine whether an organism with a dominant phenotype (e.g. green pod color) is homozygous dominant or heterozygous, you use a testcross.
2. Testcross = The breeding of an organism of unknown genotype with a homozygous recessive.
  1. If all the progeny of the testcross have green pods, then the green pod parent was probably homozygous dominant since a GG x gg cross produces Gg progeny.
  2. If the progeny of the testcross contains both green and yellow phenotypes, then the green pod parent was heterozygous since a Gg x gg cross produces Gg and gg progeny in a 1:1 ratio.
    1. The testcross was devised by Mendel and is still an important tool in genetic studies.
Inheritance as a Game of Chance
1. Segregation of allele pairs during gamete formation and reformation of pairs at fertilization obey the rules of probability.
2. The probability scale ranges from 0 to 1 with an event that is certain to occur having a probability of 1, and an event that is certain NOT to occur having a probability of 0.
3. The same rules of probability apply to tossing a coin or rolling a die.
  1. The probability of tossing a head with a two-headed coin is 1. The probability of tossing a tail with the two-headed coin is 0.
  2. The probability of tossing a head with a normal coin is 1/2 with the probability of tossing a tail also being 1/2.
  3. The probability of rolling a 3 on a six-sided die is 1/6.
  4. The probability of rolling a number other than 3 is 5/6.
4. The probabilities of all possible outcomes for an event must add up to 1.
  1. For every toss of a normal coin, the probability of heads is 1/2.
5. The outcome of any particular toss is unaffected by what has happened on previous attempts.
  1. This phenomena is referred to as independent events.
  2. It is possible the five successive tosses of a normal coin will produce five heads; however, the probability of heads on the sixth toss is still 1/2.
6. Two basic rules of probability govern the possibilities: the rule of multiplication and the rule of addition.
  1. Rule of Multiplication
    1. If two coins are tossed simultaneously, the outcome of each coin is an independent event, unaffected by the other coin.
    2. The probability that both coins will come up heads (a compound event) is equal to the product of the separate probabilities of the independent single events: 1/2 x 1/2 = 1/4.
    3. A Mendelian F1 cross with one trait which has two alleles (pea pod color) is analogous to the coin toss. With an F1 genotype of Gg, the probability that an F2 plant will have yellow pods is 1/4.
      - The probability that an egg from the F1 will receive a g allele is 1/2.
      - The probability that a sperm from the F1 will receive a g allele is also 1/2.
      - Thus the probability that two g alleles will unite at fertilization is 1/2 x 1/2 = 1/4.
7. Rule of Addition
  1. The probability that an F2 plant will be heterozygous is the sum of the two single events.
  2. Summation is used since there are two ways in which a heterozygous F2 may be produced: the dominant allele (G) may be in the egg and the recessive allele (g) in the sperm or the dominant allele may be in the sperm and the recessive in the egg.
    1. The probability that the dominant allele will be in the egg with the recessive in the sperm is 1/2 x 1/2 = 1/4.
    2. The probability that the dominant allele will be in the sperm and the recessive in the egg is 1/2 x 1/2 = 1/4.
    3. Using this rule, the probability that a heterozygous F2 will be produced is 1/4 + 1/4 = 1/2.
  The Statistical Nature of Inheritance
  1. If a seed is planted from the F2 generation, we cannot predict with absolute certainty that the plant will grow up to produce yellow pods.
  2. It can be said that there is exactly a 1/4 chance that the plant will have yellow pods.
    1. Stated in statistical terms: among a large sample of F2 plants, 25% (one-fourth) will have yellow pods.
    2. The larger the sample size, the closer the results will conform to predictions.
Mendel's Law of Independent Assortment
1. Mendel deduced the law of segregation from experiments with monohybrid crosses, breeding experiments that employ parental varieties differing in a single trait.
2. A dihybrid cross is a mating between parents that differ in two traits.
  1. Mendel performed dihybrid crosses by mating two individuals which differed in seed color (yellow and green) and seed shape (round and wrinkled).
  2. Mendel knew from monohybrid crosses that the allele for round seeds was dominant to the allele for wrinkled and that yellow was dominant to green.
3. To determine if these traits, seed shape and seed color, are inherited together or independently, Mendel performed dihybrid crosses using homozygous plants.
  1. Plants homozygous for round yellow seeds (RRYY) were crossed with plants homozygous for wrinkled green seeds (rryy).
  2. All the F1 progeny were heterozygous for both traits (RrYy) and had round yellow seeds (the dominant phenotypes).
4. The F1 generation provided no proof as to whether the traits are inherited independently or not, proof could only be obtained from an F2 generation.
  1. If segregation in the F1 plants resulted in only two classes of gametes (RY and ry) as were provided from the P generation, then the F2 generation would have a 3:1 phenotypic ratio (three-fourths round yellow seeds and one-fourth wrinkled green seeds).
  2. If segregation in the F1 plant resulted in four classes of gametes from each plant because the genes segregated independently (RY, Ry, rY, and ry), then the F2 generation would have a 9:3:3:1 phenotypic ratio (nine round yellow seeds to three round green seeds to three wrinkled yellow seeds to one wrinkled green seed).
5. Mendel allowed self-pollination of F1 plants (RrYy x RrYy) to produce an F2 generation.
  1. When he categorized peas from the F2 generation he found a ratio of 315:108:101:32 which approximates a 9:3:3:1 phenotypic ratio.
  2. The phenotypic ratio for each trait singly was still 3:1 (round vs wrinkled and yellow vs green).
  3. The experimental results supported the hypothesis that each allele pair segregates independently during gamete formation.
  4. Mendel tried all seven of his traits in various combinations in dihybrid crosses and found the same 9:3:3:1 in each case.
  5. This behavior of genes during gamete formation is called independent assortment and the principle is referred to as Mendel's Law of Independent Assortment.
6. The rules of probability applied to segregation and independent assortment can solve complex genetics problems. For example, Mendel crossed pea varieties that differed in three traits (trihybrid crosses).
  1. A trihybrid cross between two organisms with the genotypes AaBbCc and AaBbCc will result in a 1/64 probability of producing an offspring with the genotype aabbcc.
    Aa x Aa: probability for aa offspring = 1/4
    Bb x Bb: probability for bb offspring = 1/4
    Cc x Cc: probability for cc offspring = 1/4
  2. Because segregation of each allele pair is an independent event, the rule of multiplication is used to calculate the overall probability that the offspring will be aabbcc: 1/4 aa x 1/4 bb x 1/4 cc = 1/64
  3. Mendel's two laws explain inheritance in terms of discrete factors (genes) which as passed from generation to generation according to simple rules of chance.
  4. These principles apply to all sexually reproducing organisms for simple patterns of inheritance.
    1. Experiments with many organisms indicate that more complicated patterns of inheritance exist.
    2. The more complicated patterns of inheritance include situations where one allele is not completely dominant over another allele, there are more than two alleles for a trait, or the genotype does not always dictate the phenotype in a rigid manner.

P generation:	GG x gg
	green yellow

F₁ generation:	Gg x Gg
	green green

F₂ generation: