Mendel and the Gene - Comprehensive Notes

Mendel and the Gene

Overview

• This chapter covers Mendel's principles, chromosome theory of inheritance, extensions to Mendel's principles and human inheritance.

Mendel's Experimental System

• Gregor Mendel established rules of heredity using garden peas in 1865.
• Walter Sutton and Theodor Boveri proposed the chromosome theory of inheritance in 1902.
• Genetics is the branch of biology focused on inheritance.
• Heredity: transmission of traits from parents to offspring.
• Trait: any characteristic of an individual.
• Mendel aimed to understand heredity.
• Prevailing hypotheses during Mendel's time:
  • Blending inheritance: parental traits blend, offspring have intermediate traits (e.g., black sheep + white sheep = gray sheep).
  • Inheritance of acquired characteristics: parental traits are modified through use and passed on (e.g., giraffes stretch necks, offspring have longer necks).

Model Organism

• Model organism: a species used for research that is practical to work with, and conclusions can be applied to other species.
• Mendel chose peas because they are inexpensive, easy to grow, have short generation time, produce large numbers of seeds, allow controlled matings, and have polymorphic traits.
• Polymorphic traits appear in two or more different forms that are easily distinguishable (e.g., purple versus white flowers).

Control of Matings

• Peas normally self-fertilize (self-pollinate).
• Male organs produce pollen grains (sperm).
• Female organs produce eggs.
• Pollen falls on the female organ of the same flower.
• Mendel prevented self-pollination by removing male organs before pollen formed.
• He used pollen from one flower to fertilize another through cross-pollination.

Traits Studied

• Phenotype: observable features.
• Mendel's peas had two distinct phenotypes for each of seven traits.
• Mendel worked with pure lines that produced identical offspring when self-fertilized.
• He used these plants to create hybrids by mating two different pure lines that differed in one or more traits.

Experiments with a Single Trait

• Mendel's first experiments involved crossing pure lines differing in one trait (seed shape).
• Monohybrid cross: mating parents with two different phenotypes for a single trait.
• Adults in the cross = parental generation.
• Offspring = F1 generation ("first filial").
• Subsequent generations = F2, F3, etc.
• In monohybrid crosses with round and wrinkled seeds, all F1 offspring had round seeds, contradicting blending inheritance.
• The genetic determinant for wrinkled seeds seemed to disappear but reappeared in the F2 generation after F1 progeny self-pollinated.

Dominant and Recessive Traits

• Genetic determinant for wrinkled seeds is recessive.
• Genetic determinant for round seeds is dominant.
• Dominance is not an indication of fitness but indicates which trait is masked and which is observed.
• Mendel repeated experiments with each of the seven traits; the dominant trait was always present in a 3:1 ratio over the recessive trait in the F2 generation.

Reciprocal Cross

• To determine if biological sex influenced inheritance, Mendel performed a reciprocal cross.
• Mother’s phenotype in the first cross is the father’s phenotype in the second cross, and vice versa.
• The results of the two crosses were identical.
• Conclusion: It does not matter whether the genetic determinants come from the male or female parent.

Particulate Inheritance

• Mendel proposed particulate inheritance.
• Hereditary determinants do not blend or change through use but act as discrete, unchanging particles.

Mendelian Genetics Vocabulary

• Autosomal inheritance: Patterns of inheritance of genes not on a sex chromosome.
• Gene: Hereditary factor influencing a particular trait.
• Allele: A particular form of a gene.
• Genotype: Listing of alleles of particular genes in an individual.
• Phenotype: An individual's observable traits.
• Homozygous: Having two of the same allele.
• Heterozygous: Having two different alleles.
• Dominant allele: An allele that produces its phenotype in heterozygous and homozygous genotypes.
• Recessive allele: An allele that produces its phenotype only in homozygous genotypes.
• Pure line: Individuals of the same phenotype that, when crossed, always produce offspring with the same phenotype.
• Hybrid: Offspring from crosses between homozygous parents with different genotypes.
• Reciprocal cross: A cross in which the phenotypes of the male and female are reversed.
• Testcross: A cross of a homozygous recessive individual and an individual with the dominant phenotype but unknown genotype.
• X-linked: Referring to a gene located on the X chromosome.
• Y-linked: Referring to a gene located on the Y chromosome.

Genes, Alleles, and Genotypes

• Hereditary determinants for a trait are called genes.
• Each individual has two versions of each gene (alleles).
• Different alleles are responsible for variation in traits.
• Individuals get two alleles per gene, but many alternatives may exist in the population (e.g., blood types).
• One allele may "mask" another (i.e., in F1) but could be visible in offspring that get two recessive alleles (i.e., in F2).
• Genotype: the combination of alleles found in an individual. It has a profound effect on phenotype.

The Principle of Segregation

• The two members of each gene pair Segregate into different gamete cells during the formation of eggs and sperm in the parents.
• Reason: One allele per homolog; separate in Meiosis I.
• Mendel used letters to indicate genes; for example, R represented the dominant allele for seed shape, and r represented a recessive allele.
• Individuals have two alleles of each gene:
  • Homozygous: have two copies of the same allele (RR or rr).
  • Heterozygous: have two different alleles (Rr).
• Offspring of pure-line individuals (homozygotes) have the same phenotype as parents.
• Offspring of mating between two different pure lines (RR and rr) are heterozygotes with the dominant phenotype.
• Cross between two heterozygous parents:
  • Offspring are \frac{1}{4} RR, \frac{1}{2} Rr, \frac{1}{4} rr.
  • Produces a 3:1 ratio of phenotypes.
  • Punnett squares show how it works.

Punnett Square

• Write each unique gamete genotype for one parent along the top of the diagram.
• Write each unique gamete genotype for the other parent down the left side of the diagram.
• Fill in each box with the gamete genotypes above and to the left of that box.
• Calculate the proportions or ratios of each offspring genotype and phenotype.

Mendel's Model

• Peas have two copies of each gene and thus may have two different alleles of the gene.
• Genes are particles of inheritance that do not blend together.
• Each gamete contains one copy of each gene (one allele).
• Males and females contribute equally to the genotype of their offspring.
• Some alleles are dominant to other alleles.

The Dihybrid Cross

• Mendel used dihybrid crosses: mating between parents that are both heterozygous for two traits.
• Question: Do alleles of different genes segregate together or independently?
• Tested two contrasting hypotheses:
  • Independent assortment: alleles of different genes are transmitted independently of each other.
  • Dependent assortment: the transmission of one allele depends on the transmission of another.
• Mendel’s results supported the principle of independent assortment.
• The Punnett square from a dihybrid cross predicts:
  • 9 different offspring genotypes and 4 phenotypes.
  • Four possible phenotypes should be present in a ratio of 9:3:3:1.
  • Therefore, alleles of different genes are transmitted independently of one another.

Testcross

• In a testcross, a homozygous recessive parent is mated with a parent that has the dominant phenotype but an unknown genotype.
• The genotype of the 2nd parent can be inferred from the results.
• Mendel used testcrosses to further confirm the principle of independent assortment.

Chromosome Theory of Inheritance

• Based on observations of meiosis.
• States that genes are located on chromosomes at a particular locus.
• Physical separation of alleles (i.e., R, r) during meiosis I is responsible for Mendel’s principle of segregation.
• Genes for different traits assort independently at meiosis I because they are located on different non-homologous chromosomes that have two equally likely ways of lining up before being separated.

Testing the Chromosome Theory

• Thomas Hunt Morgan used fruit flies (Drosophila melanogaster) as a model organism for genetics.
• Morgan’s first goal was to identify different phenotypes.
• Wild type (WT) = most common phenotype for each trait.
• Other phenotypes arise by mutation.
• Mutants = individuals with traits caused by mutations.

The White-Eyed Mutant

• Red eyes = WT eye color in fruit flies.
• White eyes are a mutation.
• Morgan mated a WT female with a mutant male.
• All of the F1 progeny had red eyes.
• Morgan did the reciprocal cross: white-eyed female with red-eyed male.
• F1 females had red eyes, but F1 males had white eyes.

Sex Linkage and the Chromosome Theory

• X and Y chromosomes = sex chromosomes; they determine the sex of the offspring.
• Females have two X chromosomes.
• Males have an X and a Y chromosome.
• Sex-linked inheritance: occurs when a gene is located on a sex chromosome (X-linked or Y-linked inheritance).
• Autosomal inheritance: occurs with genes on non-sex chromosomes.
• Sex chromosomes pair during meiosis I and separate; gametes get either an X or a Y chromosome.
• Females produce all X gametes; males produce \frac{1}{2} X and \frac{1}{2} Y gametes.
• Morgan proposed that the gene for white eye color in fruit flies is on the X chromosome.
• When reciprocal crosses give different results (it matters if a trait comes from the mom vs. dad), it is likely that the gene is sex-linked.

Linkage

• Linkage: the tendency of genes to be inherited together because they are on the same chromosome.
• Linked genes are predicted to always be transmitted together during gamete formation and should violate the principle of independent assortment.

Crossing Over

• Morgan performed an experiment mating two flies that were heterozygous for two sex-linked traits (eye color and body color).
• Gametes with new, recombinant genotypes were generated when crossing over occurred during prophase of meiosis I.
• Linked genes are inherited together unless crossing over occurs, in which case genetic recombination occurs.
• Genes are more likely to cross over when they are far apart from each other.
• The percentage of recombinant offspring can be used to estimate the relative distance between genes.

Genetic Map

• Frequency of crossing over can be used to create a genetic map: a diagram showing the relative positions of genes along a particular chromosome.
• Crossing over occurs at random – the shorter the distance between genes, the less likely crossover will occur between them.
• Frequency of recombinant offspring correlates directly with the distance between two genes; 19.6% recombinant offspring, for example, is equal to 19.6 map units (centiMorgans, cM).

Multiple Alleles

• Multiple allelism: >2 alleles of a gene exist in a population.
• Example: Humans have 3 common alleles for ABO blood types (I^A, I^B, and i), each coding for a version of an enzyme that adds polysaccharides to the membrane of red blood cells.

Codominance

• Alleles of a gene are not always dominant or recessive; some display codominance.
• Neither allele is dominant or recessive to the other.
• Heterozygotes display the phenotype of both alleles.
• Example: ABO blood types; both I^A and I^B are dominant to i, and I^AI^B heterozygotes produce both polysaccharides, resulting in the AB blood type.

Incomplete Dominance

• Some alleles display incomplete dominance.
• Heterozygotes have an intermediate phenotype.
• Pure-line plants with red flowers (RR) crossed to pure-line plants with white flowers (rr) result in Rr offspring having pink flowers.

Pleiotropic Genes

• Most genes influence more than one trait.
• Pleiotropic genes influence many traits.
• For example, Marfan syndrome involves a single gene; mutations in the gene lead to a wide array of phenotypes.

Gene-By-Environment Interaction

• Most phenotypes are strongly influenced by the environment as well as by genotypes.
• Gene-by-environment interaction: combined effect of genes and environment (e.g., temperature, nutrients, sunlight, hormones in utero).
• The human genetic disease phenylketonuria (PKU) is an example of a gene-by-environment interaction: Individuals with PKU are homozygous recessive for a gene that codes for an enzyme which converts phenylalanine to tyrosine. The enzyme is absent, phenylalanine accumulates and produces severe mental impairment. Individuals placed on a low-phenylalanine diet develop normally.

Gene-Gene Interaction

• Multiple genes may work together to control a single trait.
• Comb shape in chickens: controlled by two genes (R and P).
• The R allele is expressed differently depending on which allele of P is present.

Quantitative Traits

• Mendel worked with discrete traits (characteristics clearly different from each other).
• Traits that vary continuously are called quantitative traits (e.g., human height and skin color).
• Plots of quantitative traits often form a bell-shaped curve, or normal distribution.
• Nilsson-Ehle used wheat to explain quantitative traits: kernel color exhibited a normal distribution of color between white and dark red.
• He proposed that quantitative traits result from the action of many genes called polygenic inheritance. Each gene adds a small amount to the value of the phenotype.

Exceptions and Extensions to Mendel's Rules

• Sex linkage: A gene is located on a sex chromosome.
• Linkage: Two or more genes are on the same chromosome.
• Incomplete dominance: Heterozygotes have an intermediate phenotype.
• Codominance: Heterozygotes have phenotypes of both alleles.
• Multiple allelism: In a population, there are more than two common alleles for a locus.
• Polymorphism: In a population, there is more than one phenotype associated with a single gene.
• Pleiotropy: A single gene affects many traits.
• Gene-gene interaction: The phenotype associated with an allele depends on which alleles of another gene are present.
• Gene-environment interaction: Phenotype is influenced by the environment experienced by individuals with the same genotype.
• Polygenic inheritance of quantitative traits: A trait that exhibits continuous variation rather than coming in distinct types.

Human Inheritance

• Cannot make experimental crosses in humans; must instead analyze genotypes and phenotypes that already exist.
• Mode of transmission describes a trait as autosomal or sex-linked and the type of dominance.
• Pedigrees (family trees) are used to learn the mode of transmission for a given trait.

Autosomal Recessive Traits

• If a phenotype is due to an autosomal recessive allele:
  • Individuals with the trait must be homozygous (i.e., ss).
  • Unaffected parents of an affected individual are likely to be heterozygous for the trait (i.e., Ss) (carriers).
  • Recessive phenotype appears in offspring only when both parents have that recessive allele.

Autosomal Dominant Traits

• If a trait is autosomal dominant, homozygous (HH) or heterozygous (Hh) individuals will display the trait.
• One heterozygous parent will pass it on to about half of his/her offspring (kids are Hh or hh).
• Any child with the trait must have a parent with the trait (unless a new mutation occurred in a gamete).

Identifying Traits as Autosomal or Sex-Linked

• If a trait appears equally often in males and females, it is likely to be autosomal.
• If males express the trait more often, it is usually X-linked.

X-Linked Recessive Traits

• X-linked recessive traits are common.
• Men (XY) will exhibit the trait if they inherit it from their mothers.
• Women (XX) will exhibit the trait only if they are homozygous.
• Usually skips a generation.
• An affected male can pass it only to his daughters.
• Daughters will pass the allele to about half their sons.

X-Linked Dominant Traits

• X-linked dominant traits are rare.
• An affected male passes the trait to all his daughters but none of his sons because daughters receive his only X chromosome.
• A female carrier will pass the trait to half her daughters and half her sons because both sexes receive one of her X chromosomes.

Y-Linked Traits

• Inheritance of Y-linked traits can be predicted.
• However, very few genes are on the Y chromosome.
• All the genes are involved with male sexual development.
• There are no other known human Y-linked traits.