23  Discussion Questions

23.1 Think Deeply About What You’ve Learned

This chapter contains thought-provoking questions to test your understanding and encourage deeper thinking about genomics and proteomics!

23.2 How to Prove DNA Is Genetic Material?

23.2.1 The Question

If you lived in the 1940s before the famous experiments, how would YOU prove that DNA (not protein) is the genetic material?

23.2.2 Think About:

What you need to show:

  • Genetic material must carry information

  • It must be copied accurately

  • It must be passed from parent to offspring

  • Changes in it must cause changes in traits

Possible approaches:

1. Transformation Experiments (like Griffith):

  • Transfer genetic material between organisms

  • See if traits transfer

  • Then identify what molecule was transferred

2. Chemical Analysis:

  • Compare DNA vs. protein in chromosomes

  • Which molecule shows more variation?

  • Which correlates with heredity?

3. Treatment Experiments:

  • Destroy DNA specifically (with DNase enzyme)

  • Does heredity still work?

  • Destroy protein specifically (with protease enzyme)

  • Does heredity still work?

4. Labeling Experiments (like Hershey-Chase):

  • Tag DNA and protein differently

  • See which enters cells during infection

  • See which appears in offspring

23.2.3 Your Turn!

Design an experiment to prove DNA is genetic material. Consider:

  • What organism would you use? (bacteria, viruses, plants, animals?)

  • What techniques are available?

  • What results would prove your hypothesis?

  • What controls would you need?

23.3 Why Are Plant Genomes Larger?

23.3.1 The Question

We learned that plants often have much larger genomes than animals. An onion has 5 times more DNA than a human! Why is this?

23.3.2 Review the Reasons:

1. Plants Don’t Move:

  • Animals need efficient cells for movement

  • Large genomes are costly (more DNA to replicate)

  • Plants can afford the extra DNA

2. Polyploidy:

  • Plants tolerate multiple genome copies

  • Wheat has 6 sets of chromosomes!

  • Animals usually can’t survive polyploidy

3. Transposable Elements:

  • “Jumping genes” accumulate in plant genomes

  • Some plants are >90% transposable elements

  • Less pressure to remove them

4. Less DNA Deletion:

  • Animals efficiently delete unnecessary DNA

  • Plants less so

  • “Junk DNA” accumulates over time

23.3.3 Discussion Points:

Question 1: Is a larger genome a disadvantage for plants? Why or why not?

Think about:

  • Energy cost of replicating more DNA

  • But plants make energy from sunlight (abundant!)

  • Larger cells (more DNA = larger nucleus = larger cell)

  • But plants don’t move anyway

Question 2: Could this change with climate change?

Consider:

  • If resources become scarce

  • If plants need to adapt quickly

  • Smaller genomes might become advantageous

  • Or polyploidy might help adaptation!

Question 3: Why do some plants (like pufferfish) have very compact genomes?

Answer hints:

  • Pufferfish need buoyancy

  • Smaller cells help float

  • Shows environmental pressures CAN favor small genomes

23.4 How Does Alternative Splicing Expand Protein Diversity?

23.4.1 The Question

Humans have only ~20,000 genes but make 100,000+ different proteins. How does alternative splicing explain this?

23.4.2 Review Alternative Splicing:

Remember:

  • Genes have exons (coding) and introns (non-coding)

  • Exons can be included or excluded

  • Different combinations → different proteins

Example:

  • Gene with exons 1, 2, 3, 4, 5

  • Could make:

    • Protein A: 1-2-3-4-5

    • Protein B: 1-2-4-5 (skip exon 3)

    • Protein C: 1-3-4-5 (skip exon 2)

    • Protein D: 1-2-5 (skip exons 3 and 4)

23.4.3 Calculate Diversity:

Math time!

If a gene has 10 exons, and each can be included or excluded:

  • That’s 2^10 = 1,024 possible proteins!

  • From ONE gene!

Extreme example:

  • DSCAM gene in fruit flies

  • Can produce 38,000 different proteins

  • From one gene!

23.4.4 Discussion Points:

Question 1: What are the advantages of alternative splicing?

Advantages:

  • More proteins without more genes

  • Saves space in genome

  • Fine-tuned regulation (different proteins in different tissues)

  • Evolutionary flexibility

Question 2: What are the disadvantages?

Disadvantages:

  • Complex regulation needed

  • Mistakes can happen (wrong splicing → disease)

  • Harder to predict proteins from DNA sequence

Question 3: Why don’t prokaryotes use alternative splicing?

Think about:

  • Prokaryotes have no introns!

  • Simpler, more direct gene expression

  • Don’t need the complexity

  • Different lifestyle (single cells, respond quickly to environment)

23.5 What Does the C-Value Paradox Teach Us About Evolution?

23.5.1 The Question

The C-value paradox shows that genome size doesn’t correlate with complexity. What does this teach us about evolution?

23.5.2 Key Lessons:

1. Evolution Doesn’t Always Optimize

  • Not everything is perfectly designed

  • “Good enough” often survives

  • Extra DNA isn’t harmful enough to be removed

  • Evolution works with what’s there, not ideal designs

Question: Does this surprise you? Why or why not?

2. Different Solutions for Different Lifestyles

  • Compact genomes work for some organisms (pufferfish)

  • Large genomes work for others (lungfish, onions)

  • No single “best” strategy

  • Context matters!

Question: Can you think of other examples in evolution where different solutions work equally well?

3. Complexity Comes from Regulation, Not Raw Material

  • It’s HOW you use genes, not how many you have

  • Like cooking: A master chef can make amazing food with simple ingredients

  • A novice cook might waste fancy ingredients

Question: How does this apply to human intelligence vs. other animals?

4. The Importance of Non-Coding DNA

  • Used to think “junk DNA” was useless

  • Now we know much of it regulates genes

  • The “junk” paradox helped us discover this!

Question: What else might we be wrong about that seems like “junk”?

23.5.3 Broader Implications:

For understanding life:

  • Life is complex in unexpected ways

  • Simple measurements (genome size) don’t capture complexity

  • Need to look deeper

For medicine:

  • Can’t judge genes by quantity alone

  • Regulation matters as much as genes themselves

  • Epigenetics is crucial!

For technology:

  • Biological systems inspire engineering

  • Efficiency isn’t always the goal

  • Redundancy and flexibility have value

23.6 How Does Genome Organization Affect Sequencing and Analysis?

23.6.1 The Question

We’ve learned about chromosome structure, packaging, and organization. How do these affect our ability to sequence and analyze genomes?

23.6.2 Challenges:

1. Repetitive DNA

Problem:

  • Many genomes have lots of repeated sequences

  • Short sequencing reads can’t tell repeats apart

  • Like trying to assemble a puzzle with many identical pieces!

Solution:

  • Long-read sequencing spans repeats

  • Can see which repeat is which

Question: Why do you think it took until 2022 to complete the human genome when the first draft was in 2000?

2. Heterochromatin

Problem:

  • Tightly packed DNA is hard to sequence

  • Centromeres, telomeres were gaps in original human genome

  • Very repetitive, very condensed

Solution:

  • Better sequencing technology

  • Long reads

  • Specialized methods

3. DNA Modifications

Problem:

  • DNA methylation affects how DNA behaves

  • Standard sequencing doesn’t detect modifications

  • Lost information!

Solution:

  • Bisulfite sequencing for methylation

  • Third-generation sequencing detects modifications directly

4. Chromosome Structure

Problem:

  • Genes interact across long distances

  • Enhancers can be far from genes they control

  • 3D structure matters!

Solution:

  • Hi-C and other 3D genome mapping methods

  • Capture chromosome conformation

23.6.3 Applications:

Disease Understanding:

  • Structural variants (large chromosomal changes) cause disease

  • Repeats can expand and cause disease (Huntington’s)

  • Understanding 3D structure reveals regulation

Evolution:

  • Chromosome rearrangements drive evolution

  • Gene order matters

  • Comparing organization across species

23.6.4 Discussion:

Question 1: If you were designing the “perfect” genome for easy sequencing and analysis, what would it look like?

Possible features:

  • No repeats

  • No introns

  • Evenly spaced genes

  • No heterochromatin

  • Linear (not circular)

  • Medium-sized

Question 2: But would that “perfect” genome be good for the organism? Why or why not?

Trade-offs:

  • Repeats have functions!

  • Introns allow alternative splicing

  • Heterochromatin regulates genes

  • Complexity enables complexity!

Question 3: How might future technology overcome current limitations?

Ideas:

  • Even longer reads

  • Real-time 3D genome imaging

  • Single-molecule sequencing in living cells

  • AI to predict structure from sequence

23.7 Synthesis Questions

23.7.1 Connecting Everything Together

Big Question 1: How do the genome, transcriptome, proteome, and epigenome work together?

Think about:

  • Genome: The instruction manual (static)

  • Transcriptome: Which instructions are being read (dynamic)

  • Proteome: The workers doing jobs (dynamic)

  • Epigenome: Bookmarks and highlights (semi-stable)

  • They all interact and influence each other!

Big Question 2: If you could sequence anything, what would you choose and why?

Options:

  • Your own genome?

  • An endangered species?

  • Microbes in your gut?

  • Ancient DNA from fossils?

  • Soil microbes?

  • Tumor cells?

Big Question 3: What’s the next big breakthrough in genomics/proteomics?

Possibilities:

  • Routine gene therapy for all genetic diseases?

  • Complete understanding of non-coding DNA?

  • Cheap real-time genome sequencing?

  • Sequencing in living organisms (no extraction)?

  • Full protein structure prediction for all proteins?

  • Understanding consciousness through genomics?

23.8 Key Takeaways

  • Critical thinking is essential in science

  • One experiment can answer big questions (if cleverly designed)

  • Trade-offs exist in biology (no perfect solution)

  • Complexity comes from organization, not just components

  • Technology limits and enables discovery

  • Big questions often have complex answers

  • Keep asking “why?” and “how do we know?”

These questions don’t have single right answers. They’re meant to make you think deeply about what you’ve learned. Discuss with others, do more research, and form your own conclusions!