Chapter Notes

Principles of Inheritance and Variation

Genetics is the branch of biology that studies inheritance and the variation of characters from parents to offspring.

• Inheritance is the process by which characteristics are passed from parent to their children (progeny). It is the basis of heredity.
• Variation is the degree to which progeny differ from their parents. Humans have long known that variation is linked to sexual reproduction and have used it for selective breeding of plants and animals, like creating the Sahiwal cow breed in Punjab from ancestral wild cows.

Mendel's Laws of Inheritance

Gregor Mendel, through his experiments on garden peas for seven years (1856-1863), laid the foundation for understanding inheritance.

Why Mendel chose pea plants:

• He could study clear, contrasting traits (e.g., tall vs. dwarf, yellow vs. green seeds).
• He used statistical analysis and mathematical logic, which was new to biology at the time.
• He used large sample sizes, making his data more credible.
• He worked with true-breeding pea lines, which are plants that consistently produce offspring with the same traits after self-pollination.

Mendel studied seven pairs of contrasting traits in pea plants (Table 4.1):

1. Stem height: Tall/dwarf
2. Flower colour: Violet/white
3. Flower position: Axial/terminal
4. Pod shape: Inflated/constricted
5. Pod colour: Green/yellow
6. Seed shape: Round/wrinkled
7. Seed colour: Yellow/green

Inheritance of One Gene (Monohybrid Cross)

A monohybrid cross is a cross that studies the inheritance of a single character (like plant height).

Mendel crossed true-breeding tall pea plants with true-breeding dwarf pea plants.

• The parent generation is called the P generation.
• The first generation of offspring is called the Filial 1 or $F_1$ generation. All plants in the $F_1$ generation were tall. The dwarf trait seemed to disappear.
• When Mendel self-pollinated the tall $F_1$ plants, he produced the Filial 2 or $F_2$ generation. In this generation, some offspring were dwarf.
• The ratio of tall to dwarf plants in the $F_2$ generation was approximately 3:1.
• Importantly, there was no "blending" of traits; plants were either tall or dwarf, not of an in-between height.

Mendel's Conclusions from the Monohybrid Cross:

• Something was being passed down from parents to offspring. Mendel called them 'factors'; today we call them genes.
• Genes are the units of inheritance and contain the information to express a particular trait.
• Genes that code for a pair of contrasting traits are known as alleles. They are slightly different forms of the same gene. For example, the gene for height has two alleles: one for tallness and one for dwarfness.

Key Terminology:

• Alleles: Represented by letters. A capital letter (e.g., T for tall) is used for the trait seen in the $F_1$ generation (dominant), and a small letter (e.g., t for dwarf) for the other trait (recessive).
• Genotype: The genetic makeup of an organism, represented by the pair of alleles (e.g., $TT$, $Tt$, or $tt$).
• Phenotype: The observable physical characteristic of an organism (e.g., tall or dwarf).
• Homozygous: An organism with an identical pair of alleles for a trait (e.g., $TT$ or $tt$).
• Heterozygous: An organism with a dissimilar pair of alleles for a trait (e.g., $Tt$).

Dominance and Recessiveness:

• In a heterozygous pair of alleles ($Tt$), one allele expresses itself and masks the effect of the other.
• The allele that expresses itself is the dominant allele (T for tall).
• The allele that is masked is the recessive allele (t for dwarf).
• This is why all $F_1$ plants with genotype $Tt$ were tall.

Punnett Square: Developed by British geneticist Reginald C. Punnett, the Punnett Square is a graphical tool used to predict the probability of all possible genotypes of offspring in a genetic cross.

Let's look at the monohybrid cross for height using a Punnett Square (Figure 4.4):

1. Parental (P) cross: A homozygous tall plant ($TT$) is crossed with a homozygous dwarf plant ($tt$).
2. Gametes: The tall parent produces only T gametes. The dwarf parent produces only t gametes.
3. $F_1$ Generation: All offspring have the genotype $Tt$ and the phenotype tall.
4. $F_1$ Self-cross: A heterozygous tall plant ($Tt$) is self-pollinated.
5. Gametes from $F_1$: Each $F_1$ plant produces two types of gametes in equal proportion: T and t.
6. $F_2$ Generation: The Punnett square shows the possible combinations:
   • Genotypic Ratio: 1 $TT$ : 2 $Tt$ : 1 $tt$ (or 1:2:1)
   • Phenotypic Ratio: 3 Tall : 1 Dwarf (or 3:1), because both $TT$ and $Tt$ genotypes result in a tall phenotype.

This 1:2:1 ratio can be represented by the binomial expansion $(1/2 \mathbf{T} + 1/2 \mathbf{t})^2 = 1/4 \mathbf{TT} + 1/2 \mathbf{Tt} + 1/4 \mathbf{tt}$.

Test Cross: It's impossible to know the genotype of a tall plant just by looking at it (it could be $TT$ or $Tt$). A test cross is used to determine the genotype of an organism showing a dominant phenotype.

• Procedure: The organism with the unknown dominant genotype is crossed with a homozygous recessive parent (e.g., a tall plant is crossed with a dwarf plant, $tt$).
• Analysis (See Figure 4.5):
  • If the unknown plant is homozygous dominant ($TT$), all offspring of the test cross will be heterozygous ($Tt$) and show the dominant phenotype (all tall).
  • If the unknown plant is heterozygous ($Tt$), the offspring will have a 1:1 ratio of dominant to recessive phenotypes (half tall, half dwarf).

Law of Dominance (Mendel's First Law)

Based on the monohybrid cross, Mendel proposed the Law of Dominance, which states:

1. Characters are controlled by discrete units called factors (genes).
2. Factors occur in pairs.
3. In a dissimilar pair of factors (heterozygous), one member of the pair dominates the other (recessive).

This law explains why only one parental trait is expressed in the $F_1$ generation and why a 3:1 phenotypic ratio is observed in the $F_2$ generation.

Law of Segregation (Mendel's Second Law)

This law is based on the fact that alleles do not blend and that both traits are recovered in the $F_2$ generation.

• The law states that during gamete formation (meiosis), the two alleles of a gene pair segregate (separate) from each other, so that each gamete receives only one of the two alleles.
• A homozygous parent ($TT$ or $tt$) produces only one type of gamete.
• A heterozygous parent ($Tt$) produces two types of gametes (T and t) in equal proportions.

Deviations from Mendelian Inheritance

Incomplete Dominance

Sometimes, the $F_1$ generation has a phenotype that is "in-between" the two parental phenotypes. This is called incomplete dominance.

• A cross between a true-breeding red-flowered plant ($RR$) and a true-breeding white-flowered plant ($rr$) is made.
• The $F_1$ generation ($Rr$) is not red or white, but pink. This shows that the R allele is not completely dominant over the r allele.
• When the pink $F_1$ plants are self-pollinated, the $F_2$ generation shows a phenotypic ratio of 1 Red ($RR$) : 2 Pink ($Rr$) : 1 White ($rr$).
• In this case, the genotypic ratio (1:2:1) is the same as the phenotypic ratio.

Explanation of the Concept of Dominance

A gene contains information to produce a product, often an enzyme. In a diploid organism, there are two copies (alleles) of each gene. Let's assume a normal allele produces a functional enzyme. A modified allele could:

1. Produce a normal or less efficient enzyme.
2. Produce a non-functional enzyme.
3. Produce no enzyme at all.

In case 1, the phenotype is unchanged. In cases 2 and 3, the phenotype depends on the unmodified (functional) allele. This functional allele is considered the dominant allele, as it produces the original phenotype. The modified, non-functional allele is the recessive allele.

Co-dominance

In co-dominance, the $F_1$ generation resembles both parents because both alleles express themselves fully and independently when present together.

• ABO blood groups are controlled by the gene I, which has three alleles: $I^A$, $I^B$, and $i$.
• Alleles $I^A$ and $I^B$ produce slightly different sugar molecules on the surface of red blood cells. Allele $i$ produces no sugar.
• $I^A$ and $I^B$ are both completely dominant over $i$. So, a person with genotype $I^Ai$ has blood type A, and a person with $I^Bi$ has blood type B.
• When $I^A$ and $I^B$ are present together (genotype $I^A I^B$), both alleles express themselves, producing both types of sugars. This results in blood type AB. This is co-dominance.
• A person with genotype $ii$ has blood type O.

Multiple Alleles The ABO blood group system is also an excellent example of multiple alleles, where a single gene has more than two alleles ($I^A$, $I^B$, and $i$) in a population. However, any individual can only have two of these alleles at a time.

Inheritance of Two Genes (Dihybrid Cross)

A dihybrid cross studies the inheritance of two characters simultaneously.

Mendel crossed pea plants with round, yellow seeds ($RRYY$) and wrinkled, green seeds ($rryy$).

• Dominant traits: Yellow (Y) is dominant over green (y), and Round (R) is dominant over wrinkled (r).
• $F_1$ Generation: All offspring had the genotype $RrYy$ and the phenotype round and yellow.
• $F_1$ Self-cross: When the $RrYy$ plants were self-pollinated, the $F_2$ generation showed four different phenotypes.
• $F_2$ Phenotypic Ratio: The traits appeared in a ratio of 9 Round-Yellow : 3 Wrinkled-Yellow : 3 Round-Green : 1 Wrinkled-Green (9:3:3:1).

Law of Independent Assortment (Mendel's Third Law)

Based on the dihybrid cross, Mendel proposed the Law of Independent Assortment.

• The law states that when two pairs of traits are combined in a hybrid, the segregation of one pair of characters is independent of the other pair of characters.
• This means the allele a gamete receives for seed shape (R or r) does not influence the allele it receives for seed color (Y or y).
• An $F_1$ plant ($RrYy$) produces four types of gametes in equal proportions: $RY$, $Ry$, $rY$, and $ry$.
• The 9:3:3:1 ratio is a combination of two separate 3:1 ratios: (3 Round : 1 Wrinkled) × (3 Yellow : 1 Green).

Chromosomal Theory of Inheritance

Mendel's work, published in 1865, went unrecognized until 1900 for several reasons:

• Poor communication and publicity.
• His concept of discrete "factors" (genes) that didn't blend was contrary to the idea of continuous variation seen in nature.
• His use of mathematics in biology was new and not widely accepted.
• He could not provide physical proof for the existence of factors.

In 1900, de Vries, Correns, and von Tschermak independently rediscovered Mendel's laws. By this time, scientists could observe chromosomes during cell division.

In 1902, Walter Sutton and Theodore Boveri noted that the behavior of chromosomes during meiosis was parallel to the behavior of Mendel's genes. This led to the Chromosomal Theory of Inheritance.

Comparison of Gene and Chromosome Behavior:

Sutton and Boveri argued that the pairing and separation of chromosomes during meiosis would lead to the segregation of the gene pairs (factors) they carried. They proposed that genes are located on chromosomes.

Linkage and Recombination

Thomas Hunt Morgan provided experimental verification of the Chromosomal Theory of Inheritance through his work with fruit flies, Drosophila melanogaster.

Why Drosophila?

• Short life cycle (about two weeks).
• Can be grown easily in a lab.
• A single mating produces many offspring.
• Clear differentiation between males and females.
• Many observable hereditary variations.

When Morgan performed dihybrid crosses in Drosophila for genes that were sex-linked (located on the X chromosome), he found that the $F_2$ ratio did not follow the expected 9:3:3:1.

• He observed that the proportion of parental gene combinations was much higher than non-parental combinations.
• Morgan concluded that this was because the two genes were physically located on the same chromosome.

Key Terms:

• Linkage: The physical association of genes on the same chromosome. Linked genes tend to be inherited together.
• Recombination: The generation of non-parental gene combinations, which occurs due to crossing over between homologous chromosomes during meiosis.

Morgan found that the strength of linkage varied:

• Tightly linked genes: Genes located very close together on a chromosome show very low recombination (e.g., yellow body and white eyes in Drosophila showed only 1.3% recombination).
• Loosely linked genes: Genes located farther apart on a chromosome show higher recombination (e.g., white eyes and miniature wings showed 37.2% recombination).

Morgan's student, Alfred Sturtevant, used the frequency of recombination between gene pairs as a measure of the distance between them and created the first genetic maps.

Polygenic Inheritance

While Mendel studied traits with distinct forms (tall/dwarf), many traits show a continuous range of variation. These are called polygenic traits.

• Polygenic inheritance is when a trait is controlled by three or more genes.
• The environment can also influence the expression of these traits.
• The effect of each allele is additive, meaning each dominant allele contributes to the phenotype.

• Assume skin color is controlled by three genes (A, B, C).
• The dominant alleles (A, B, C) are responsible for dark skin, and the recessive alleles (a, b, c) for light skin.
• A person with genotype $AABBCC$ will have the darkest skin.
• A person with genotype $aabbcc$ will have the lightest skin.
• A person with an intermediate number of dominant alleles (e.g., $AaBbCc$) will have an intermediate skin color.

Human height is another example of a polygenic trait.

Pleiotropy

Pleiotropy is when a single gene influences multiple, seemingly unrelated phenotypic traits.

• PKU is caused by a mutation in a single gene that codes for the enzyme phenylalanine hydroxylase.
• This single gene defect leads to multiple phenotypic effects:
  • Mental retardation.
  • Reduction in hair and skin pigmentation.

The underlying mechanism is often that the gene's product (e.g., an enzyme) is involved in multiple metabolic pathways.

Sex Determination

The mechanism by which the sex of an individual is established is called sex determination. The initial clues came from studies of insects.

• Henking (1891) observed a nuclear structure in some insects that he called the X body. He saw that 50% of sperm received it, while 50% did not. This was later identified as a chromosome.
• Chromosomes involved in determining sex are called sex chromosomes.
• All other chromosomes are called autosomes.

Types of Chromosomal Sex Determination:

1. XO Type (e.g., Grasshopper):

   • Females have a pair of X chromosomes (XX).
   • Males have only one X chromosome (XO). The 'O' indicates the absence of a second sex chromosome.
   • Males produce two types of sperm: one with an X chromosome and one without. This is an example of male heterogamety.

2. XY Type (e.g., Humans, Drosophila):

   • Females have a pair of identical X chromosomes (XX). They are homogametic.
   • Males have one X chromosome and a smaller Y chromosome (XY). They are heterogametic.
   • Males produce two types of sperm: 50% carry an X chromosome and 50% carry a Y chromosome.

3. ZW Type (e.g., Birds):

   • The sex-determining mechanism is reversed.
   • Males have a pair of identical Z chromosomes (ZZ). They are homogametic.
   • Females have one Z and one W chromosome (ZW). They are heterogametic, producing two types of eggs (one with Z, one with W).

Sex Determination in Humans

• Humans have 23 pairs of chromosomes: 22 pairs of autosomes and 1 pair of sex chromosomes.
• Females: 44 Autosomes + XX
• Males: 44 Autosomes + XY
• During meiosis, females produce only one type of egg, which always contains an X chromosome.
• Males produce two types of sperm: 50% contain an X chromosome, and 50% contain a Y chromosome.
• If an X-carrying sperm fertilizes the egg, the zygote ($XX$) develops into a female.
• If a Y-carrying sperm fertilizes the egg, the zygote ($XY$) develops into a male.

Sex Determination in Honey Bees

Honey bees have a unique system called haplodiploid sex-determination.

• Sex is determined by the number of sets of chromosomes an individual receives.
• Females (queen and workers) develop from fertilized eggs and are diploid (32 chromosomes).
• Males (drones) develop from unfertilized eggs by parthenogenesis and are haploid (16 chromosomes).

This system has interesting consequences:

• Males produce sperm by mitosis, not meiosis.
• Males do not have a father and cannot have sons, but they do have a grandfather and can have grandsons.

Mutation

A mutation is a sudden, heritable change in the DNA sequence that results in a change in the genotype and phenotype of an organism.

Types of Mutations:

• Chromosomal Aberrations: Changes affecting large segments of DNA.
  • Deletion: Loss of a DNA segment.
  • Insertion/Duplication: Gain of a DNA segment.
  • These are commonly observed in cancer cells.
• Point Mutation: A change in a single base pair of DNA.
  • A classic example is sickle-cell anemia.
• Frameshift Mutation: Deletions or insertions of base pairs that shift the "reading frame" of the genetic code.

Mutagens are physical or chemical agents that cause mutations. For example, UV radiation is a mutagen.

Genetic Disorders

Pedigree Analysis

Since controlled crosses are not possible in humans, pedigree analysis is used to study the inheritance of traits.

• A pedigree chart is like a family tree that shows the inheritance of a specific trait, abnormality, or disease over several generations.
• Standard symbols are used to represent individuals and their relationships (See Figure 4.13).
• By analyzing a pedigree, one can determine if a trait is dominant or recessive, and whether it is autosomal or sex-linked.

Mendelian Disorders

These disorders are caused by a mutation or alteration in a single gene. They follow Mendelian inheritance patterns.

• Colour Blindness: An X-linked recessive disorder. Affected individuals cannot distinguish between red and green. It is more common in males (8%) than females (0.4%) because males have only one X chromosome. A female is only colour blind if her father is colour blind and her mother is at least a carrier.
• Haemophilia: An X-linked recessive disorder where a protein required for blood clotting is defective. A simple cut can lead to non-stop bleeding. It is transmitted from a carrier female to her male offspring. Queen Victoria was a famous carrier of this disease.
• Sickle-cell Anaemia: An autosomal recessive disorder. It is caused by a point mutation in the gene for the beta-globin chain of haemoglobin.
  • The amino acid Glutamic acid (Glu) is replaced by Valine (Val) at the sixth position.
  • The gene substitution is from GAG to GUG.
  • Under low oxygen, the mutant haemoglobin polymerizes, causing red blood cells to change from a biconcave disc to a sickle-like shape.
  • Genotypes: $Hb^A Hb^A$ (Normal), $Hb^A Hb^S$ (Carrier, sickle-cell trait), $Hb^S Hb^S$ (Affected with disease).
• Phenylketonuria (PKU): An autosomal recessive disorder. An affected individual lacks the enzyme to convert the amino acid phenylalanine to tyrosine. Phenylalanine accumulates and is converted to phenylpyruvic acid, which can cause mental retardation.
• Thalassemia: An autosomal recessive blood disorder resulting in a reduced rate of synthesis of one of the globin chains (α or β) of haemoglobin.
  • α Thalassemia: Production of the α-globin chain is affected. Controlled by two genes (HBA1, HBA2) on chromosome 16.
  • β Thalassemia: Production of the β-globin chain is affected. Controlled by a single gene (HBB) on chromosome 11.

Chromosomal Disorders

These are caused by the absence, excess, or abnormal arrangement of one or more chromosomes.

• Aneuploidy: The gain or loss of one or more chromosomes, caused by the failure of chromatids to segregate during cell division.
• Polyploidy: An increase in a whole set of chromosomes, often seen in plants.

Examples of Aneuploidy in Humans:

• Down's Syndrome (Trisomy 21):
  • Cause: Presence of an additional copy of chromosome 21. The karyotype is 47 chromosomes.
  • Symptoms: Short stature, small round head, furrowed tongue, partially open mouth, broad palm with a single palm crease, and retarded physical, psychomotor, and mental development.
• Klinefelter's Syndrome:
  • Cause: Presence of an additional X chromosome in a male, resulting in a karyotype of 47, XXY.
  • Symptoms: Overall masculine development, but with some feminine features like breast development (Gynaecomastia). Individuals are sterile.
• Turner's Syndrome:
  • Cause: Absence of one X chromosome in a female, resulting in a karyotype of 45, XO.
  • Symptoms: Females are sterile as ovaries are rudimentary. They also lack other secondary sexual characteristics and have short stature.