Bacterial Genetics

COMPLETE STUDY GUIDE — TOPIC 4
ONPS2431 Molecular Biology & Genetics
RMIT University — Semester 1, 2026
TECHNIQUES USED IN THIS GUIDE:
First-Principles Explanations • Analogy-Based Teaching • Active Recall Questions • Comparison Tables • Mnemonics • 40 Self-Test Questions

TABLE OF CONTENTS

  • 1The Big Picture — Why Bacteria Share DNA
  • 2Vertical vs Horizontal Gene Transfer
  • 3Genetic Variation — Why It Matters
  • 4Transformation — Naked DNA Uptake
  • 5Conjugation — Direct Cell-to-Cell Transfer
  • 6Hfr Bacteria — High Frequency Recombination
  • 7Transduction — Viral-Mediated Gene Transfer
  • 8Lytic vs Lysogenic Cycles
  • 9Key Comparison Tables
  • 10Mnemonics & Memory Aids
HOW TO USE THIS GUIDE

Step 1: Read each section — they build on each other. Step 2: After each section, cover the page and explain from memory. Step 3: Use the comparison tables to distinguish the three transfer methods. Step 4: Do all 40 questions. Mark gaps for re-study.

1

The Big Picture

Why bacteria share DNA and why molecular biologists exploit this

Topic 3 covered the 5 steps of molecular cloning: isolate gene, insert into vector, transform into host, screen, culture. Topic 4 zooms in on Step 3 — transformation — and explains the biological mechanisms behind it. Molecular biologists did not invent gene transfer in bacteria — they co-opted natural systems that bacteria evolved over billions of years to share genetic material.

Bacteria are described as promiscuous — they readily share DNA with each other through multiple mechanisms. Understanding these natural mechanisms is essential because: (1) they are the basis for laboratory transformation techniques, (2) they explain how antibiotic resistance spreads between bacteria, and (3) they are a major source of genetic variation in prokaryotes.

KEY INSIGHT

Molecular cloning works because bacteria naturally take up, share, and integrate foreign DNA. The lab techniques simply make these natural processes more efficient and controlled. Every time you transform E. coli with a plasmid, you are exploiting a system that bacteria evolved for horizontal gene transfer.

2

Vertical vs Horizontal Gene Transfer

Two fundamentally different ways genetic information moves

Vertical gene transfer is the standard inheritance we think of — DNA is passed from a parent cell to its daughter cells during cell division. Every daughter gets a copy of the parent's chromosome (and any plasmids). This is how genetic information normally flows down through generations.

Horizontal gene transfer (HGT) is the transfer of genetic material between cells that are NOT parent and offspring — often between completely unrelated bacteria. This is unique to prokaryotes (eukaryotes use sexual reproduction for genetic mixing). HGT occurs by three mechanisms: transformation, transduction, and conjugation. These are the focus of this topic.

3

Genetic Variation

Why diversity matters and what happens without it

Genetic variation is the raw material for evolution. Without variation, a population cannot adapt to changing environments — a single disease, antibiotic, or environmental change could wipe out every individual. Horizontal gene transfer is one of the main ways bacteria generate genetic variation (alongside mutation).

Eukaryotes generate variation primarily through sexual reproduction (meiosis + fertilisation = recombination of parental genomes). Prokaryotes do not reproduce sexually — they divide by binary fission, producing clones. Instead, they rely on horizontal acquisition (transformation, conjugation, transduction) to gain new genes from other bacteria.

LACK OF VARIATION = DANGER

Inbreeding is the result of reproduction between closely related individuals, reducing genetic variation. In agriculture, monocultures (genetically identical crops) are devastated by single diseases — e.g., the Irish Potato Famine. In bacteria, a population without HGT is vulnerable to a single antibiotic. Variation = survival insurance.

4

Transformation

Uptake of naked DNA from the environment

4 Uptake of naked DNA from the environment Transformation is the unidirectional transfer of free (naked) DNA from the environment into a bacterial cell, resulting in a phenotypic change in the recipient. The DNA may come from dead lysed bacteria in the environment. The recipient cell must be competent — able to take up DNA through its membrane.

Figure 2: Natural transformation — (1) recipient cell takes up naked donor DNA fragments, (2) donor DNA aligns with

homologous region on chromosome, (3) recombination integrates donor genes, (4) genetically transformed cell results.

Griffith’s Experiment (1928) — Proof of Transformation

Frederick Griffith demonstrated transformation using Streptococcus pneumoniae: he showed that heat-killed virulent (smooth, S) bacteria could transfer their virulence trait to living non-virulent (rough, R) bacteria. The R bacteria were ‘transformed’ into S bacteria by taking up DNA released from the dead S cells. This was the first evidence that DNA carries genetic information. Laboratory Transformation (what you do in the lab) In the lab, transformation is made more efficient by artificially making cells competent using CaCl + heat 2 shock (42°C) or electroporation. You are exploiting the same natural mechanism — just making it happen more reliably with your recombinant plasmid.

5

Conjugation

Direct cell-to-cell DNA transfer via a sex pilus

5

Direct cell-to-cell DNA transfer via a sex pilus

Conjugation is the unidirectional transfer of DNA from a donor cell (F+) to a recipient cell (F-) through direct physical contact via a structure called the sex pilus (plural: pili). The pilus acts as a bridge between the two cells.

Figure 3: Conjugation — the F+ (donor) cell extends a sex pilus to the F- (recipient) cell. The F factor (plasmid) is replicated and

one copy is transferred through the pilus. Result: both cells are now F+.

The F Factor (Fertility Factor)

The F factor is a special plasmid (also called the sex factor) that carries the genes for pilus formation and DNA transfer. Cells carrying the F factor are called F+ (donors); cells without it are F- (recipients). During conjugation, a copy of the F factor is transferred from F+ to F-, converting the recipient into an F+ cell.

Importantly, only the F plasmid is transferred — chromosomal genes are NOT transferred in standard F+ ×

F- conjugation. KEY POINT In standard conjugation (F+ × F-), only the F plasmid is transferred. The recipient becomes F+ but does NOT receive any chromosomal genes from the donor. Chromosomal gene transfer requires Hfr cells (Section 6). Hfr Bacteria 6 High Frequency Recombination — when the F factor integrates into the chromosome Figure 4: Formation of an Hfr cell — the F factor integrates into the bacterial chromosome by recombination. The cell can now transfer chromosomal genes during conjugation. Sometimes, the F factor undergoes a rare recombination event and integrates directly into the bacterial chromosome. When this happens, the cell is called an Hfr cell (High frequency recombination). The F factor is no longer a separate plasmid — it is now part of the chromosome. Why Hfr matters: When an Hfr cell conjugates with an F- cell, it starts transferring DNA from the integrated F factor — but because the F factor is now embedded in the chromosome, chromosomal genes adjacent to the integration site are also dragged along. This means Hfr conjugation can transfer chromosomal genes to the recipient — something standard F+ conjugation cannot do. However, complete transfer of the entire chromosome (including the rest of the F factor) rarely happens because the conjugation bridge usually breaks before transfer is complete. So the recipient typically gets some chromosomal genes but does NOT become F+ (it stays F-).

6

Hfr Bacteria

High Frequency Recombination — when the F factor integrates into the chromosome

Sometimes, the F factor undergoes a rare recombination event and integrates directly into the bacterial chromosome. When this happens, the cell is called an Hfr cell (High frequency recombination). The F factor is no longer a separate plasmid — it is now part of the chromosome.

Why Hfr matters: When an Hfr cell conjugates with an F- cell, it starts transferring DNA from the integrated F factor — but because the F factor is now embedded in the chromosome, chromosomal genes adjacent to the integration site are also dragged along. This means Hfr conjugation can transfer chromosomal genes to the recipient — something standard F+ conjugation cannot do.

However, complete transfer of the entire chromosome (including the rest of the F factor) rarely happens because the conjugation bridge usually breaks before transfer is complete. So the recipient typically gets some chromosomal genes but does NOT become F+ (it stays F-).

7

Transduction

Viral-mediated gene transfer between bacteria

7

Viral-mediated gene transfer between bacteria

Transduction is the transfer of bacterial DNA from one cell to another mediated by a bacteriophage (phage) — a virus that infects bacteria. During the phage life cycle, bacterial DNA can accidentally get packaged into phage particles and delivered to a new host cell when that phage infects again. Key terminology: (cid:127) Bacteriophage (phage): A virus that infects bacteria. Example: phage T4 and phage lambda (l) both infect E. coli. (cid:127) Prophage: Phage DNA that has integrated into the bacterial chromosome. It is non-infective and replicates with the host. (cid:127) Lytic cycle: Phage replicates, destroys (lyses) the host cell, and releases new phage particles. (cid:127) Lysogenic cycle: Phage DNA integrates into the host chromosome as a prophage and replicates passively with the host — no lysis. Lytic vs Lysogenic Cycles 8 Two possible fates when a phage infects a bacterium

Figure 5: Lytic cycle (left) — phage replicates and lyses the cell. Lysogenic cycle (right) — phage integrates as a prophage,

replicates with host, and can later excise and enter the lytic cycle.

The Lytic Cycle (Destruction)

(cid:127) Phage attaches to bacterium and injects its DNA. (cid:127) Phage DNA hijacks the cell’s machinery to replicate phage DNA and make phage proteins. (cid:127) New phage particles are assembled inside the cell. (cid:127) The cell lyses (bursts open), releasing ~100-200 new phages. (cid:127) Each new phage can infect another bacterium. The host is destroyed.

The Lysogenic Cycle (Integration)

(cid:127) Phage attaches and injects DNA (same as lytic). (cid:127) Instead of replicating, the phage DNA integrates into the bacterial chromosome by recombination, becoming a prophage. (cid:127) The prophage is replicated passively every time the bacterium divides — all daughter cells carry the prophage. (cid:127) The bacterium is NOT destroyed — it grows and divides normally (called a lysogenic bacterium). (cid:127) Under stress, the prophage can excise from the chromosome and enter the lytic cycle. Generalised vs Specialised Transduction 9 Two types of accidental gene transfer by phages

Figure 6: (a) Generalised transduction — random bacterial DNA packaged into phage during lytic cycle. (b) Specialised

transduction — specific genes adjacent to prophage integration site carried along during imprecise excision in lysogenic cycle.

Feature Generalised Transduction Specialised Transduction
Cycle involved Lytic cycle Lysogenic cycle
What DNA is Only genes adjacent to the prophage
Any random fragment of bacterial chromosome
transferred integration site
During lytic replication, bacterial DNA is
During excision, the prophage cuts imprecisely
How it happens accidentally packaged into a phage head
and takes adjacent bacterial genes with it
instead of phage DNA
Specificity Random — any gene can be transferred Specific — only genes near the integration site
Frequency Rare (accidental packaging error) Rare (imprecise excision error)
Phage particle Hybrid: some phage DNA + adjacent bacterial
Bacterial DNA only (no phage DNA)
contains DNA
How Cloning Exploits Bacterial Genetics
10
Connecting Topic 3 and Topic 4
Now you can see the full picture of how molecular cloning works by exploiting natural bacterial systems:
Cloning Step Natural System Exploited Lab Technique
Step 3: Transform Natural transformation (uptake of naked CaCl2 + heat shock or electroporation makes E. coli
vector into host DNA) artificially competent
Plasmids are natural extrachromosomal
Plasmid Cloning vectors are engineered plasmids with ori,
DNA elements that replicate
replication in host MCS, and selectable markers
independently
8

Lytic vs Lysogenic Cycles

Two possible fates when a phage infects a bacterium

The Lytic Cycle (Destruction)

• Phage attaches to bacterium and injects its DNA. • Phage DNA hijacks the cell's machinery to replicate phage DNA and make phage proteins. • New phage particles are assembled inside the cell. • The cell lyses (bursts open), releasing ~100-200 new phages. • Each new phage can infect another bacterium. The host is destroyed.

The Lysogenic Cycle (Integration)

• Phage attaches and injects DNA (same as lytic). • Instead of replicating, the phage DNA integrates into the bacterial chromosome by recombination, becoming a prophage. • The prophage is replicated passively every time the bacterium divides — all daughter cells carry the prophage. • The bacterium is NOT destroyed — it grows and divides normally (called a lysogenic bacterium). • Under stress, the prophage can excise from the chromosome and enter the lytic cycle.

Generalised vs Specialised Transduction

FeatureGeneralised TransductionSpecialised Transduction
Cycle involvedLytic cycleLysogenic cycle
What DNA is transferredAny random fragment of bacterial chromosomeOnly genes adjacent to the prophage integration site
How it happensRandom bacterial DNA packaged into phage head instead of phage DNAProphage cuts imprecisely and takes adjacent bacterial genes
SpecificityRandom — any gene can be transferredSpecific — only genes near the integration site
9

Key Comparison Tables

Three Horizontal Gene Transfer Mechanisms
FeatureTransformationConjugationTransduction
DNA sourceFree (naked) DNA in environmentLiving donor cell (F+ or Hfr)Bacteriophage (virus)
Transfer mechanismUptake of naked DNA through membraneSex pilus forms bridge; DNA transferred directlyPhage injects DNA into new host
Cell contact required?No — DNA is free in the environmentYes — direct cell-to-cell contact via pilusNo — phage acts as intermediary
DNA transferredRandom chromosomal fragmentsF plasmid (F+) or chromosomal genes (Hfr)Random fragments (generalised) or specific genes (specialised)
DirectionUnidirectional (donor → recipient)Unidirectional (donor → recipient)Unidirectional (phage → new host)

F+, F-, and Hfr Cells

Cell TypeF Factor LocationCan Donate DNA?What Is Transferred?
F+ (donor)Free plasmid in cytoplasmYes (to F- cells)F plasmid only (no chromosomal genes)
F- (recipient)AbsentNoN/A — receives DNA
HfrIntegrated into chromosomeYes (to F- cells)Chromosomal genes (+ partial F factor). Recipient usually stays F-
10

Mnemonics & Memory Aids

Lock these into long-term memory

Three HGT Methods: TCT

MNEMONIC

Transformation, Conjugation, Transduction = Naked DNA, direct contact, phage-mediated. Three ways bacteria share genes horizontally.

Transformation = Naked

MNEMONIC

Transformation = Naked DNA from environment = No cell contact needed. DNA floats free. Griffith proved it with S. pneumoniae.

Conjugation = Contact

MNEMONIC

Conjugation = direct Contact via sex pilus = F+ donor sends F plasmid to F- recipient through the pilus bridge.

Transduction = Taxi

MNEMONIC

Transduction = phage is the Taxi for bacterial DNA = Virus accidentally carries bacterial DNA to a new host.

F+/F-/Hfr

MNEMONIC

F+ = has F plasmid (free). F- = no F factor. Hfr = F integrated into chromosome. = F+ × F- = only F plasmid transferred. Hfr × F- = chromosomal genes transferred.

Lytic = Lethal

MNEMONIC

Lytic cycle = cell Lyses = dies = phage wins = Phage replicates, assembles, bursts the cell. Destruction.

Lysogenic = Lurking

MNEMONIC

Lysogenic = phage Lurks as prophage in chromosome = No lysis. Phage integrates, hides, replicates with host. Can reactivate under stress.

Generalised = Grab bag

MNEMONIC

Generalised transduction = any random gene grabbed by accident = Lytic cycle; random bacterial DNA packaged into phage head.

Specialised = Specific neighbours

MNEMONIC

Specialised transduction = specific genes next to prophage site = Lysogenic cycle; imprecise excision takes adjacent bacterial genes.

11

Active Recall — 40 Questions

Cover the answers. Write yours first. Then check.
HOW TO USE THIS SECTION

Read → Write answer → Compare → Mark wrong → Re-study. Repeat until 100%.

Q1. What is horizontal gene transfer (HGT)?

Q2. Name the three mechanisms of HGT in bacteria.

Q3. How does vertical gene transfer differ from horizontal?

Q4. Why is genetic variation important for bacteria?

Q5. How do eukaryotes generate genetic variation?

Q6. How do prokaryotes generate genetic variation without sexual reproduction?

Q7. Define transformation.

Q8. What does 'competent' mean in transformation?

Q9. Describe Griffith's experiment and what it proved.

Q10. How do molecular biologists make bacteria competent in the lab?

Q11. Define conjugation.

Q12. What is the F factor?

Q13. What is the sex pilus and its role?

Q14. In standard F+ × F- conjugation, what DNA is transferred?

Q15. What is an Hfr cell?

Q16. How does Hfr conjugation differ from standard F+ conjugation?

Q17. Does F- recipient become F+ after Hfr conjugation?

Q18. Define transduction.

Q19. What is a bacteriophage?

Q20. What is a prophage?

Q21. Describe the lytic cycle.

Q22. Describe the lysogenic cycle.

Q23. What triggers a prophage to excise and enter the lytic cycle?

Q24. What is generalised transduction?

Q25. What is specialised transduction?

Q26. In generalised transduction, does the phage particle contain phage DNA?

Q27. In specialised transduction, what does the phage particle contain?

Q28. Which cycle is involved in generalised transduction?

Q29. Which cycle is involved in specialised transduction?

Q30. Compare transformation, conjugation, and transduction in one sentence each.

Q31. Is cell-to-cell contact required for transformation?

Q32. Is cell-to-cell contact required for conjugation?

Q33. Is cell-to-cell contact required for transduction?

Q34. How does molecular cloning exploit natural transformation?

Q35. How do phage vectors exploit transduction?

Q36. A student says 'F+ cells transfer chromosomal genes to F- cells during conjugation.' Is this correct?

Q37. What is the key structural difference between an F+ cell and an Hfr cell?

Q38. Why can't bacteria rely on mutation alone for genetic variation?

Q39. How does antibiotic resistance spread between bacterial species?

Q40. Name the three HGT mechanisms, state whether cell contact is needed, and name the DNA vehicle for each.

YOU MADE IT — NOW CONSOLIDATE

Today: Do all 40 questions on paper. Mark misses.

Tomorrow: Re-read marked sections. Focus on the comparison table (transformation vs conjugation vs transduction).

Day 3: All 40 cold. Nail them all = you own this topic.

Before exam: The three-way comparison table and the lytic vs lysogenic cycle diagram are the most tested areas. Also make sure you understand F+, F-, and Hfr.

Score: 0/0