Midterm

Chapter 4: Sex Determination & Sex Chromosomes

1⃣ Introduction: Why Does Sex Differ?

Sex determination is the biological system that decides whether an organism develops as male or female. Different species use different mechanisms to determine sex, and this chapter explores those genetic, chromosomal, and environmental factors.

2⃣ Mechanisms of Sex Determination

Different species have different ways to determine sex. Here are the four main systems:

3⃣ Environmental Sex Determination

In some species, sex is not determined by chromosomes but by external conditions, such as temperature or social behavior.

1⃣ Temperature-Dependent Sex Determination (TSD) 🐢🐊

• Example: Turtles, alligators

• How it works: Temperature at which eggs develop determines sex.

  • Low temp = Female

  • High temp = Male

2⃣ Behavioral Sex Determination 🐠

• Example: Clownfish

• How it works: Clownfish are protandrous hermaphrodites (they start as males but can switch to females if needed).

• If the dominant female dies, the largest male changes into a female to maintain reproduction.

4⃣ Dosage Compensation & X-Chromosome Inactivation

Since females have two X chromosomes (XX) while males have only one (XY), the expression of X-linked genes must be equalized between sexes. Dosage compensation ensures that males and females produce similar amounts of X-linked gene products.

How Different Species Handle Dosage Compensation?

X-Inactivation: The Lyon Hypothesis

• Proposed by Mary Lyon in 1961.

• In females (XX), one X chromosome is randomly inactivated during early development.

• The inactivated X chromosome forms a dense, compact structure called a Barr body.

Real-Life Example: Calico Cats 🐱

• The orange and black fur patches result from random X-inactivation in different cells.

• One X chromosome carries the orange fur gene, and the other carries the black fur gene.

• Only females (XX) can be calico because they have two X chromosomes!

5⃣ X-Linked Inheritance

Some genes are located on the X chromosome, and their inheritance follows different rules from autosomal genes.

Why are X-linked traits more common in males?

• Males have only one X chromosome (XY), so they express whatever allele is present on their single X.

• Females (XX) have two copies of X-linked genes, so they can be carriers without showing symptoms.

Key Patterns in X-Linked Inheritance:

1. Fathers pass their X chromosome to daughters only (not sons).

2. Mothers pass their X chromosome to both sons & daughters.

3. Males are hemizygous (only one X copy), so recessive X-linked traits appear more often in them.

Examples of X-Linked Traits

🩸 Hemophilia A (Royal Disease)

• A recessive X-linked disorder that prevents normal blood clotting.

• Affected males (XʰY) cannot pass the trait to their sons but all daughters will be carriers (XʰX).

🧬 Duchenne Muscular Dystrophy (DMD)

• X-linked recessive disorder that leads to muscle degeneration.

• Males (XᴰY) are affected more often, while females (XᴰX) are usually carriers.

6⃣ Morgan’s Experiment with Drosophila

• Thomas Hunt Morgan studied fruit flies (Drosophila melanogaster) to prove that genes are located on chromosomes.

• He discovered the white-eye mutation was sex-linked (on the X chromosome).

Morgan’s Crosses

1. White-eyed Male (XʷY) × Red-eyed Female (Xʷ⁺Xʷ⁺)

   • All offspring had red eyes.

   • F1 males inherited Xʷ⁺ (red) from their mother, and Y from their father.

2. F1 Cross: Red-eyed Female (Xʷ⁺Xʷ) × Red-eyed Male (Xʷ⁺Y)

   • Produced F2 generation with 3 red-eyed: 1 white-eyed ratio

   • Only males showed the white-eyed phenotype (XʷY), proving X-linkage.

Key Takeaway:

Genes can be inherited on the X chromosome, affecting males and females differently!

7⃣ Syndromes & X-Inactivation

Because X-inactivation adjusts gene dosage, it also affects individuals with abnormal numbers of X chromosomes.

Chapter 5: Extensions of Mendelian Inheritance 🎓

Dominant & Recessive Alleles

Wild-Type vs. Mutant Alleles

• Wild-type allele → Common in a population (normal function).

• Mutant allele → Less common, results from mutations.

Why Are Most Mutant Alleles Recessive?

1. 50% of normal protein is enough for a normal phenotype.

2. Upregulation of the normal allele compensates for the mutated one.

2⃣ Types of Dominant Mutations

1. Gain-of-Function Mutation

• The gene gains a new function or becomes overactive.

• Example: A mutation in a growth factor gene can cause uncontrolled cell growth (cancer).

2. Dominant-Negative Mutation

• The mutant allele produces a protein that interferes with the normal protein.

• Example: A defective collagen protein weakens connective tissue (Marfan syndrome).

3. Haploinsufficiency

• One functional allele is not enough to maintain normal function.

• Example: Polydactyly (extra fingers/toes) occurs when one copy of the gene is insufficient.

3⃣ Penetrance & Expressivity

Incomplete Penetrance

• Some individuals with the dominant allele do not show the phenotype.

• Example: Polydactyly – Some people with the dominant allele (P) have normal fingers.

Variable Expressivity

• A trait varies in severity among individuals with the same genotype.

• Example: Neurofibromatosis – Some individuals have a few skin spots, while others have tumors.

4⃣ Environmental Effects on Gene Expression

Norm of Reaction

• The range of phenotypes caused by environmental influences on a genotype.

• Example: Arctic foxes are brown in summer and white in winter due to temperature-sensitive fur color.

5⃣ Non-Mendelian Inheritance Patterns

1. Incomplete Dominance

• The heterozygote has a blended phenotype between the two homozygotes.

• Example: Red (RR) × White (WW) → Pink (RW) in Four-o’clock plants.

2. Codominance

• Both alleles are fully expressed in heterozygotes.

• Example: AB blood type → Expresses both A and B antigens.

3. Overdominance (Heterozygote Advantage)

• Heterozygotes have a survival advantage over homozygotes.

• Example: Sickle Cell Trait

  • SS (Homozygous Normal) → No disease, but vulnerable to malaria.

  • ss (Homozygous Sickle Cell) → Severe disease.

  • Ss (Heterozygote) → Resistant to malaria + mild sickle cell effects.

6⃣ Sex-Influenced vs. Sex-Limited Traits

Sex-Influenced Traits

• Autosomal traits where dominance depends on sex.

• Example: Scurs in cattle

  • ScP (dominant in males, recessive in females)

  • A ScPScA male has scurs, but a ScPScA female does not.

Sex-Limited Traits

• Traits that occur in only one sex due to hormonal control.

• Example: Milk production in cows, beard growth in men.

7⃣ Lethal Alleles & Pleiotropy

Lethal Alleles

• Cause death before birth or in early life.

• Example: Manx Cats

  • Homozygous dominant (MM) = lethal

  • Heterozygous (Mm) = Short tail (Manx cat)

  • Homozygous recessive (mm) = Normal tail

Pleiotropy

• One gene affects multiple traits.

• Example: Cystic Fibrosis (CFTR gene mutation)

  • Lungs → Thick mucus buildup

  • Pancreas → Digestive issues

  • Sweat glands → Salty sweat

8⃣ Gene Interactions

1. Epistasis

• One gene masks the expression of another.

• Example: Labrador retriever coat color:

  • E gene (pigment deposition) masks B gene (black/brown pigment).

  • ee genotype = Yellow lab, no matter what B gene is present.

2. Complementation

• Two parents with recessive mutations produce a normal offspring.

• Example: Two deaf parents (aaBB × AAbb) have a child with normal hearing (AaBb).

3. Gene Redundancy

• Two or more genes perform the same function, so a mutation in one does not cause a loss of function.

• Example: A plant still produces a leaf pigment even if one of the pigment genes is mutated.

Chapter 6: Extranuclear Inheritance 🌍🔬

Mendelian genetics explains how traits are passed through nuclear genes, but some traits are inherited outside the nucleus. Extranuclear inheritance refers to the transmission of genetic material found in mitochondria and chloroplasts.

1⃣ What is Extranuclear (Cytoplasmic) Inheritance?

• Most genes are in the nucleus, but mitochondria and chloroplasts also have their own DNA (mtDNA and cpDNA).

• These organelles are inherited maternally because the egg contributes most of the cytoplasm.

• Traits do not follow Mendelian inheritance (no dominant/recessive patterns).

🔬 Key Concept: Organelles like mitochondria and chloroplasts have circular DNA and replicate independently of the nucleus!

2⃣ Endosymbiotic Theory: Why Do Mitochondria & Chloroplasts Have DNA?

💡 The Endosymbiotic Theory suggests that mitochondria and chloroplasts originated from bacteria that were engulfed by early eukaryotic cells.

🛠 Evidence for the Endosymbiotic Theory:

1. Mitochondria & Chloroplasts have their own circular DNA (like bacteria).

2. They have a double membrane (suggesting they were engulfed).

3. They divide by binary fission (like bacteria).

4. Their ribosomes are similar to bacterial ribosomes, not eukaryotic ribosomes.

🧬 Origins of Organelles:

3⃣ Chloroplast Inheritance (Maternal)

• Most plants inherit chloroplast DNA from the mother (maternal inheritance).

• In some plants, chloroplasts can be biparental (both parents) or paternal.

🔬 Example: Mirabilis jalapa (Four O’Clock Plant)

• Leaves can be green, white, or variegated (green & white patches).

• The color is determined by the chloroplasts in the egg cytoplasm, not nuclear DNA.

• A heteroplasmic cell (with green & white chloroplasts) randomly distributes organelles, leading to different leaf patterns.

4⃣ Mitochondrial Inheritance (Maternal)

• Mitochondria are also maternally inherited in most species (e.g., humans).

• Sperm contribute very few mitochondria to the zygote, and they are usually destroyed.

🔬 Key Concept: Maternal inheritance = Offspring inherit mitochondria from the egg only!

🧬 Rare Exception: Paternal Leakage

• Sometimes, a few sperm mitochondria enter the egg and survive.

• Example: 1-4 paternal mitochondria per 100,000 maternal mitochondria in mice.

5⃣ Mitochondrial Diseases

Because mitochondria provide energy (ATP production), mutations in mtDNA often affect high-energy-demand organs like muscles, brain, and eyes.

1. Leber Hereditary Optic Neuropathy (LHON)

• Affects vision due to damage in the optic nerve.

• Mutations in mitochondrial genes that produce ATP.

2. Mitochondrial Myopathy

• Causes muscle weakness and neurological problems.

• Results from mutations in mtDNA that affect energy production.

🔬 Key Concept: Mitochondrial diseases show maternal inheritance (passed from mother to all children, but never from father to children).

6⃣ Epigenetic Inheritance: Modifications That Change Gene Expression

Epigenetics refers to heritable changes in gene expression that do NOT change the DNA sequence.

Genomic Imprinting: One Parent’s Gene is Silenced

• One allele is "marked" (methylated) and silenced in offspring.

• Only the allele from the other parent is expressed!

• This breaks Mendelian inheritance, because gene expression depends on parental origin.

🔬 Example: Igf2 (Insulin-like Growth Factor 2)

• Paternally imprinted → Only the father’s Igf2 allele is expressed.

• Mother’s Igf2 allele is silenced (methylated).

7⃣ Maternal Effect Genes

• In the maternal effect, the mother’s genotype directly determines the offspring’s phenotype.

• This is NOT the same as maternal inheritance (which involves extranuclear DNA).

🔬 Example: Lymnaea Snails (Shell Coiling)

• Snails can have right-handed (dextral) or left-handed (sinistral) shell coiling.

• The mother’s genotype (not the offspring’s own genes) determines coiling.

• Even if the offspring is genetically dd, they will still have dextral shells if their mother was Dd.

• This happens because mRNA and proteins from the mother affect early embryonic development.