Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Advance Genetics > Test III > Flashcards

Test III Flashcards

You may prefer our related Brainscape-certified flashcards:
Biology 101 flashcards
1
Q

Bacterial Genome

A
  • Usually 1 circular chromosome
  • 4-5 Mb of DNA
  • Tightly packed, DNA molecule condenses by supercoiling and looping
  • Each bacterium replicates and then divides by binary fission into 2 daughter cells.
  • Prokaryotes are haploid
  • Often contain plasmids
  • Only circular DNA molecules in prokaryotes replicate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Eukaryote genomes

A
  • Diploid

- Linear chromosome, usually more than one

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Plasmid

A
  • Small circles of double stranded DNA
  • Used as cloning vectors
  • May contain genes that benefit host bacterium or contribute to bacterial pathogenicity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Resistance plasmids

A
  • Contain transposons
  • Carry genes tat confer resistances to multiple antibiotics
  • Can be transferred from one bacterium to another in nature
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Prokaryote genomes

A
  • More than 80% of the chromosomal fraction is dedicated to protein coding genes required for growth and metabolic functions
  • 1% encodes RNA specifying genes
  • The rest comprises intergenic spacers containing regulatory signals
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Microbial variation

A
  • In comparison to eukaryotes, genome sizes in singled celled organisms varies very little
  • But bacterial display big variation in metabolic properties, cellular structures and lifestyles
  • Phenotypic diversity among species is remarkable
  • However organisational features of the genome are very well conserved
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Organisation of microbial genome

A
  • Many cellular processes within bacterial are coupled
  • Genes within bacteria are usually co transcribed
  • Genes are arranged in OPERONS
  • Functioning unit of genomic DNA containing a cluster of genes under the control of a single regulatory signal or promoter
  • The genes are transcribed together in an mRNA strand
  • Genes contained in the operon are either expressed together of not at all
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Gene transfer in Bacteria:

A

Vertical gene transfer

  • occurs in sexually reproducing organisms
  • traits are transferred from parent to offspring

Horizontal gene transfer
-Traits are introduced from unrelated individuals or from different species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Three mechanism for gene transfer in bacteria. In all three mechanisms..

A
  • Donor bacterium provides the DNA that is transferred

- Recipient bacterium receives the DNA, which results in altered phenotype

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Transformation

A
  • Lysis of donor cell releases DNA into medium
  • Donor DNA is taken up by the recipient
  • Process by which a DNA molecule is taken up from the external environment and incorporated into the genome of the recipient cell.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Conjugation

A
  • Donor DNA is transferred directly to recipient through a connecting tube.
  • Contact and transfer are promoted by a specialised plasmid in the donor cell.
  • Temporary direct contact between two bacterial cells leading to an exchange of genetic material (DNA).
  • This exchange is unidirectional, i.e. one bacterial cell is the donor of DNA and the other is the recipient.
  • In this way, genes are transferred laterally amongst existing bacterial as opposed to vertical gene transfer in which genes are passed on to offspring.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Transduction

A
  • Bacteriophage infects a cell
  • Lysis of donor cell. Donor DNA is packaged in released bacteriophage
  • Donor DNA is transferred when phage particles infects recipient cell.
  • Involves transfer genetic material from one bacterium to another by a bacteriophage.
  • Acting as a vector, the virus carries its own genome plus a fragment of DNA from the bacterium it has recently infected. If the host bacterium survives the viral attack, recombination may occur,
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Personalised Medicine

A
  • Individual respond differently to drugs and sometimes the effects are unpredictable
  • Differences in DNA that alter the expression or function of proteins that are targeted by drugs can contribute significantly to variation in the responses of individual
  • Genome based information and technologies may yield a new set of molecular diagnostic tools that can be used to individualise and optimise drug therapy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

The goal of Personalised Medicine

A
  • The right dose…
  • The right drug for….
  • The right indication for….
  • The right patient for at…
  • The right time…
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Walfarin

A
  • Multisource anticoagulant (different strength tablets)
  • Walfarin inhibits vitamin K reductase, which is the enzyme responsible for recycling oxidated vitamin K back into the system. For this reason, drugs in this class are also called vitamin K antagonists.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Walfarin doses

A

Narrow therapeutic Index
-small separation between dose response curves for prevent ing emboli and excess coagulation

Non linear dose response (INR)
-small changes in dose may cause changes in INR with a time lag

Wide ranges of doses to achieve target INR of 2-3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Walfarin Metabolism

A
  • 2 polymorphic genes, CYP2C9 and VKORC1 affect walfarin metabolism and response
  • Allelic frequencies of these two genes are usually associated with ethnicity

Concerns with prescribing patients with the 2 polymorphisms

  • overdose can result in bleeding which can be fatal
  • underdose can thrombosis which can be fatal

CYP2P9 is involved in walfarin metabolism
VKORC1 influences walfarin anticoagulation effect through vitamin K

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Influenze Subgroups

A

Influenza A

  • highly infective
  • infects many species
  • causes widespread epidemics (pandemic)

Influenza B

  • found in humans
  • capable of producing severe disease
  • causes regional epidemics

Influenza C

  • causes mild disease
  • humans are natural host, but also found in pigs
  • does not cause epidemics
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Reasons for pandemics

A
  • New flu virus occurs due to a process involving mutation and recombination of viral genomes
  • Mutations can occur in the replication process of the viral genome
  • Mixing occurs because different strains of influenza virus can exchange genes by infecting different animals
  • Avian influenza viruses can exchange genes with human influenza viruses creating hybrid stains
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Influenza Virus genome

A
  • RNA virus
  • The genome consist of 7-8 RNA fragments, each coding for a viral protein
  • 8 genes are responsible for the translation of 10-11 viral proteins.

PB2-transcriptase: cap binding
HA: Haemagglutinin
Na: Neuraminidase: release of virus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Influenza virus structure

A
  • Nucleocapsid: RNA enclosed in a protein coat
  • Surrounded by a lipid envelope
  • Two glycoproteins present: HA and NA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Influenza Virus Lifecycle

A
  1. HA binds to cell GP at a Sialic Acid binding site
  2. Clathrin-coated pit endocytoses virion
    - Conformational change: hydrophobic binding of HA to vesicle membrane
  3. RNAs are released into cytoplasm for replication and transcription (vRNA and mRNA)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Neuraminidase

A
  • Allows release of the newly formed viruses within the host

- Determinant of disease severity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Release of Newly Formed Viruses

A
  • Replicated vRNA, RNA replicases and other viral proteins are assembled into virions
  • HA and NA cluster into a cell membrane bulge
  • Virion leaves the nucleus and enters the membrane protrusion
  • Mature virus buds from cell in host membrane containing HA and NA
  • HA binding virus to cell surface via receptors containing sialic acid
  • NA cleaves receptors allowing release of virus
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Mutation of vRNA

A
  • Absence of RNA proofreading enzymes
  • RNA polymerase that copies the genome makes an error every 10 000 nucleotides
  • Majority of newly manufactured viruses are mutants
  • This enables the virus to surface antigens slowly over time

Leads to ANTIGENIC DRIFT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Antigenic Shift

A
  • More than one virus can infect a host cell at one time
  • Allows mixing of the 8 separate segments of the vRNA and reassortment
  • Rapid change in viral genetics and antigen expression

Leads to ANTIGENIC SHIFT

Both shift and drift allow the virus to evade host immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Out of African Theory

A

Suggest that Homo erectus evolved into Homo sapiens in Africa and then ventured out of Africa and dispersed to all around the world.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Multi Regional Evolution Theory

A

Suggests that Homo erectus ventured out of Africa and then evolved into modern man in several different locations through out the world

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Evidence for Molecular evolution

A
  • DNA sequencing evidence shows that modern humans originated in Africa and migrated north out of Africa then eventually to the rest of the world
  • Oldest fossils of modern humans are found in African dating around 16000 years old
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Genetic Tools

A

Fossil records

DNA sequencing

  • mtDNA: maternally inherited, female side
  • Y c/some:paternal line, complementing the mtDNA
  • Microsatellite DNA analysis: segments of tandemly repeated DNA with a short repeat length, usually 2-5 nucleotides.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

MtDNA

A

-Suggested that modern humans first appeared in Eastern Africa about 150 000 years ago and left between 35 000-89 000 years ago, eventually conquering the globe/

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Modern Humans using mtDNA

A
  • Based on mtDNA alone, “out of africa” hypothesis was correct with no introgression with local species of Homo
  • Most genetic diversity is in Africa
  • Ancestral allele are in Africa
  • Non africans are nested within the African clade (Non african alleles are a subset of African alleles)
  • Supports the scenario that H.sapies originated in African and a small subset migrated out of africa
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Y chromosome DNA study

A
  • Looked at 1200 DNA samples in Asia
  • Looked for 3 specific mutations on Y c/come known to have originated in Africa
  • Everyonne carried one of the three mutations or polymorphisms
  • Showed little/no interbreeding from Homo erectus and H.sapiens
  • Individuals are descendants from Africa
  • Likely that the early African humans emigrated to North African and made the lead to Asia and then to the rest of the world
  • Indicates that modern humans of African origin completely replaced earlier popn in East Africa
34
Q

Bioinformatics

A
  • Europeans and Asians share 1% to 4% of their nuclear DNA with Neanderthals, but Africans do not.
  • Data suggests that early modern humans interbreed with Neanderthals after modern humans left Africa, but before they spread into Asian and Europe.
35
Q

Molecular clocks

A
  • Evolutionary time can be measured with a molecular clock
  • Provides a good estimate of time of divergence because rate of evolution is constant across all lineages
  • The molecular clock hypothesis states that DNA and protein sequences evolve at a rate that is relatively constant over time and among different organisms
36
Q

Comparing proteins

A

Two highly conserved proteins are:

Cytochrome C

  • Extracts energy from nutrients in mitochondria
  • 20/104 aa occupy identical positions in all eukaryotes

Homeobox

  • Encodes TFL turn on genes during development to ensure correct anatomical position
  • Highly conserved 60 aa
  • Mutations: humans, disrupts development of fingers and toes, Cattle, double muscling
37
Q

Human Mitochondria

A

0dsDNA circular genome

  • Maternal inheritance
  • Lack of recombination
  • Mutates 10x faster than nuclear DNA.
38
Q

Benign Tumours

A

Do not spread from their site of origin but can crowd out (squash) surrounding cells e.g. brain tumour, wart

39
Q

Malignant tumours

A
  • Can spread from their original site and cause secondary tumours.
  • This is called metastasis.
  • They interfere with neighbouring cells and can block blood vessels.
40
Q

Why are secondary tumours so bad?

A

Both types of tumours can rob the body essential nutrients so the tumour can sustain rapid growth and division of the cells

41
Q

Secondary tumours

A
  • To form a secondary tumour, a tumour cell needs to leave the vessel system and invade tissue
  • The cell must attach itself to a vessels wall. Once this is done, it can work its way through the vessel and enter the tissue
  • Less than 1 in 100000 tumour cells will survive long enough to establish a new tumour,a few survivors can escape and initiate new colonies of the cancer
42
Q

Hallmarks and Characteristics

A
  • Sustaining proliferation signalling
  • Deregulating cellular energetics (hallmark)
  • Resisting cell death
  • Avoiding immune destruction (hallmark)
  • Inducing angiogenesis
  • Activating invasion and metastasis
  • Tumour promoting inflammation (characteristic)
  • Enabling replicative immortality
  • Genome instability and mutation (characteristic)
  • Evading growth suppressor
43
Q

Tumour suppressor genes

A
  • Normal role to prevent cancerous growth eg. RB gene
  • Acts as a brake by preventing cells from moving through the cell cycle e.g. RB

Expressed proteins usually have one of the two functions:

  • maintain the integrity of the genome by monitoring and/or repressing alteration in the genome –>Checkpoint protein
  • Negative regulators or inhibitors of cell division. Their function is necessary to properly halt cell division otherwise cell division is abnormally accelerated.
44
Q

Cell cycle

A

G1- cell grows in size, prepares for DNA replication
S-DNA replication
G2-Cell prepares for division
M-mitosis
1. Breakdown of nuclear membrane
2. Condensation of chromosomes
3. Attachment of chromosomes to mitotic spindles

45
Q

Cell cycle proteins

A
  • Proteins within the cell control the cell cycle
  • Signals affecting critical checkpoints determine whether the cell will divide (cyclins, kinases)

G1, M, G2 checkpoints

46
Q

CDKs and Cyclins

A

CDKs interact with cyclins and control the cell cycle by phosphorylating other proteins

CDKs=family if kinases that regulate the transition from G1 to S and from G2 to M

  • Cyclins specifies the protein target for CDK
  • Phosphorylation by CDKs can activate or inactivate a protein.
47
Q

Checkpoint proteins

A
  • Proteins called cyclins and CDK proteins are responsible for advancing a cell through the 4 phases of the cell cycle
  • Formation of activated cyclin/cdk complexes can be stopped by checkpoint proteins
  • When checkpoint genes are rendered inactive by mutation, the division of normal healthy cells may not be adversely affected.
  • In this case, additional mutations e.g. exposure to a mutagen maybe required to affect the function of the mutated checkpoint protein
48
Q

Cell cycle checkpoint ensure genomic stability

A

Checkpoints monitor the genome and cell cycle machinery before allowing progression to the nest stage of cell cycle

G1 to S checkpoint
-DNA synthesis can be delayed to allow time for repair of DNA that was damaged during G1

G2 to M Checkpoint
-Mitosis can be delayed to allow time for repair of DNA that was damaged during g2

Spindle checkpoint
-Monitors formation of mitotic spindle and engagement of all pairs of sister chromatids

49
Q

Telomeres and telomerases

A

Telomerase=enzyme (complex of RNA and protein) that adds telomere sequences to the ends of chromosomes

  • Loss of control of telomere length may also contribute to cancer
  • Normal, specialised cells have telomerase turned off, limits cell divisions
  • Cancer cells have to express telomerase to be able to divide indefinitely
50
Q

Genetic basis of Cancer

A
  • Disease characterised by uncontrolled cell division
  • Genetic disease at the genetic and cellular level
  • Cancer is classified according to what type of cell that has become cancerous

Familial or hereditary-10% cancers: higher predisposition to develop the disease as an inherited trait

Sporadic-most cancers do not involve genetic changes that are passes from parents to offspring.

51
Q

Characteristics of Cancer

A
  • Oiler, less adherent
  • Loss of the cell cycle control
  • Heritable
  • Transplantable
  • Dedifferentiated
  • Lack contact inhibition
  • Induce local blood vessel formation (angiogenesis)
  • Invasive
  • Increased mutation rates
  • Can spread (metastized)
52
Q

Two unifying themes of cancer genetics

A

Cancer is a disease of genes

  • multiple cancer phenotypes arise from mutations in genes that regulate cell growth and division
  • Environmental chemicals increase mutation rates and increase chances of cancer

Cancer has a different inheritance pattern than other genetic disorders

  • Inherited mutations can predispose to cancer, but the mutation causing cancer occur in somatic cells
  • Mutations accumulate in clonal descendents of a single cell
53
Q

Germ line mutations

A

-Cells that give rise to gametes (egg/sperm)
-Mutations originates in meiosis and affects all cells of an individual
-Increases cancer susceptibility
~50 familial forms

54
Q

Somatic cell

A
  • All cells of the body excluding germ line cells e.g. skin, muscle cells
  • Most mutations occur in somatic cells

Mutations: originate in mitosis

  • early or during development
  • affect limited area of the body
  • no transmission to offspring
55
Q

Spontaneous mutations

A
  • Errors in DNA replication
  • Toxic metabolic products
  • Changes in nucleotide structures
  • Transposons
56
Q

Induced mutations (environmental triggers)

A
  • Chemical agents
  • Changes in structure of DNA
  • Physical agents: damage DNA e.g. xrays, UV light
57
Q

Mutations in proto oncogenes convert them to oncogenes

A

Four common mutations

  1. Missense mutation e.g. ras gene
  2. Gene amplification e.g. increase copy number (e.g. myc in lung cancer)
  3. Chromosomal translocation e.g. Burkitts lymphoma
  4. Viral insertion e.g. cervical cancer

—> GAIN OF FUNCTION

58
Q

Proto-oncogene

A

=genes that normally trigger cell division.
=active when cell division necessary e.g. in an embryo or during wound healing. They have roles as secreted growth factors, signal inducing kinases and TFs (e.g RAS, MYC)

59
Q

Oncogene

A

-A gene which is associated with cancer due to mutations
Onco=”swelling, mass or tumour”
-Involved directly or indirectly in controlling the rate of cell growth

60
Q

Tumour surpressor genes

A
  • Act in a recessive way
  • Normal gene that encodes a protein that helps prevent cancer
  • Maintenance of genome integrity
  • Negative regulation of cell division
61
Q

Retinoblastoma (Rb)

A
  • Mutation in Rb gene, chromosome 13q
  • Rare, cancerous tumour in cone cell of retina. Abnormal appearance of the pupil
  • Almost always present in early childhood (birth to 4 years) and is often bilateral
  • Rb protein binds transcription factors so that they cannot activate genes that carry out mitosis
  • Normally halts the cell cycle G1
  • A negative regulator of the cell cycle through its ability to bind transcription factor E2F and repress transcription of genes required for S phase of the cell cycle
  • Study of Rb was the origin of the “two hit hypothesis” of cancer causation
62
Q

Two hit hypothesis

A

-Two mutations or deletions are required
One in each copy of the RB gene
-For sporadic cases: RB is a result of two somatic mutations

For familial cases (inherited)

  • individuals harbour one germline mutant allele for the RB gene in each of their cells
  • this is followed by a somatic mutation in the normal allele
63
Q

M-/T-tropic HIV

A

Two types of HIV strain in virus transmission

Early HIV transmission (virus in M-tropic)

  • gp120 is able to bind to CD4 and chemokine receptors, CCR5
  • found on macrophages
  • occurs in 90% cases

Late phase HIV infections (virus is T-tropic_

  • gp120 capable of binding to CD4 and chemokine receptor CXCR4
  • found on T-lymphocytes
  • phenotypic switch from M-tropic
64
Q

Retrovirus Replication Cycle

A
  1. Fusion of HIV to the host cell surface
  2. HIV RNA, reverse transcriptase, integrase and other viral proteins enter the host cell
  3. Viral DNA is reverse transcribed
  4. Viral DNA is transported across the nucleus and integrates into the host DNA
  5. New viral RNA is used as genomic RNA and to make viral proteins
  6. New viral RNA and proteins move to the cell surface and new immature HIV forms
  7. The virus matures by protease releasing individual HIV proteins
65
Q

HIV Genome: Major Genes

A

gag
= “group specific antigen”. Encodes structural proteins, capsid, matrix, nucleoprotein (RNA binding)

pol
=encodes enzyme
-proteases cleaves viral polyprotein
-RT/RNases for reverse transcription
-Intergrase cuts cell DNA to insert proviral DNA

env= “envelope”
-encodes for envelope glycoproteins; surface, transmembrane

66
Q

HIV Genome: 5’ end region

A

R-terminal 5’ end sequence (becomes 3’ end of proviral DNA, signal for poly-A addition to mRNA)

PB-primer binding site of cell tRNA

Leader-recognition sequence for packaging genome RNA donor site for all spliced sub-genomic mRNA

67
Q

HIV Genome: 3’end region

A

PP-polypurine (AUG) tract, initiation site for viral (+) DNA synthesis

U3-unique 3’ sequence (becomes 5’ end of proviral DNA), regulatory sequence for mRNA transcription and DNA replication

R-terminal repeat, for reverse transcription

68
Q

Retroviral genome

A
  • Retrovirus contains two copies of the RNA genome held together by multiple regions of base pairing
  • The RNA complex also includes two molecules of a specific celluar RNA (tRNA lys) that serves as a primer for the initiation of reverse transcription
  • The primer tRNA is partially unwound and H-bonding near the 5’ end of each RNA genome in a region called the prier binding site.
69
Q

HIV:

Activation of viral transcription

A
  • Integrated viral DNA may then lie dormant
  • ->Latent stage of HIV infection
  • ->Last up to 10 years
  • Viral replication is triggered
  • ->Host cellular treanscription factors are needed
  • NF kappa B (NFkB) is very important
  • -> unregulated in activated macrophages and T cells
  • Cells most likely to be killed by the HIV are those currently fighting infection
70
Q

HIV:

Genetic Variability-Mutations

A
  • HIV has a very high genetic variability
  • Fast replication cycle: generation of about 10^10 virions everyday
  • Hight mutation rate
  • Generation of many variants of HIV in a single infected patient in the course of one day.
71
Q

HIV:

Genetic Variability

A
  • Single cell simultaneously infected by two or more different strains of HIV
  • Genome is progeny virions maybe composed of RNA strands from different strains
  • This hybrid virion then infects a new cell where it undergoes replication
  • vRNT jumps back and fourth between the two different RNA templates
  • Newly synthesised retroviral DNA sequence that combines the two parental genomes
72
Q

Opportunistic infections Associated with AIDS

A

Bacterial

  • tuberculosis
  • strep pneumonia

Viral

  • Herpes
  • Influenza

Parasitic

  • Pneumocytis carinii
  • Cryptosporidium

Fungal

  • candida
  • Cryptococcus.
73
Q

Lambda phage

A
  • Temperate phage

- Uses both lytic and lysogenic cycles

74
Q

Bacteriophage Replication:

Lytic cycle

A

Lytic cycle= results in cell lyses and release of progeny phage

  • Phage injects its DNA into bacterial cell
  • Phage proteins are expressed and take over protein synthesis and DNA replication machinery of infected cell
  • Phage DNA replication occurs
  • Phage particles are assembled with phage DNA and protein
  • Infected cell burst releasing 100-200 viral particles able to infect other cells
75
Q

Bacteriophage Replication:

Lysogenic cycle

A
  • Does not result in immediate lysing of the host cell
  • Viral genome integrates with host DNA and replicates along with it fairly harmlessly (prophage)
  • Virus remains dormant until host conditions deteriorate, (maybe due to nutrient depletion)
  • Prophages activate and initiate the reproductive cycle resulting in lysis of the host cell
  • Lysogenic cycle allows host cell to survive and reproduce, allowing the virus to be reproduced in all cell’s offspring
76
Q

Lambda

Circularisation

A
  • Circularisation via cohesive ‘sticky’ ends (cos ends)

- Linear phage lambda chromosome in the bacteriophage particle circularises in host cell after infection

77
Q

Lambda phage Genome

A

The organisation of the genes with this circular structure reflects the two alternative life cycles of the virus

Top genes (cI, cro, CIII, O, P) are transcribed very soon after infection, at the beginning either life cycles
-Pattern if their expression determines which of the two cycles prevails

Genes of left (N, CII) of viral genome encode proteins that are responsible for the lysogenic infection

Genes on the right (Q, S, R of viral genome encode proteins responsible for the lytic infection

78
Q

Life cycle of Lambda

A
  1. Virus enters cell
  2. PL and PR gets activated
  3. PL transcribes to make N protein
  4. PR transcribes to make cro protein
  5. Termination sites stop transcription but when enough N protein is made, transcription goes past these two stop sites (you can now make cIII and cII, replication proteins (O and P) and Q)
  6. There are also termination sites next to Q protein. Q protein will allow transcription past this site.
  7. If Cro protein blocks production of cI (goes lytic)
  8. If cII and cIII activates transcription to make cI (goes lysogenic)
  9. cI blocks PL and PR (stops transcription) by binding to OL and OR.
79
Q

Genetic switch: Cellular proteases

A
  • Activity of the cII protein plays a key role in directing lambda to the lysogenic or lytic cycle
  • The cII protein is easily degraded by cellular proteases produced by E. coli
  • Whether or not these proteases are produced depends on the environmental conditions
80
Q

Cellular proteases choosing lytic cycle

A

Growth conditions are very favorable, the intracellular levels of the proteases are high
-The cII protein tends to be degraded
-Therefore, PRE cannot be activated and the lambda repressor is not made
-Instead, the cro protein slowly accumulates to high levels
-The binding of the cro protein to OR prevents transcription of the lambda repressor from PRM
-At the same time, the cro protein allows the lytic cycle to proceed
-Thus, environmental conditions that are favorable for growth promote the lytic cycle
This makes sense because a sufficient supply of nutrients is necessary to synthesize new bacteriophages

81
Q

Cellular proteases choosing lysogenic cycle

A

-If the nutrients are limiting (starvation conditions), the cellular proteases are relatively inactive
-The cII protein builds up much more quickly than cro
-Therefore, the cII protein will turn on PRE
The lambda repressor is made
-Environmental conditions that are unfavorable for growth promote the lysogenic cycle
This makes sense because there may not be sufficient nutrients for the production of new bacteriophages

82
Q

How do cells leave lysogenic cycle and go to the lytic cycle?

A

-By stress

UV light

  • recA (a cellular protein normally involved in DNA recombination) detects the DNA damage
  • It is activated to become a protease
  • It cleaves the l repressor and inactivates it
  • This allows transcription from PR
  • Therefore, the cro protein will accumulate
  • Favouring the lytic cycle
  • The exposure to UV light may have already damaged the bacterium to the point where further bacterial growth and division are prevented

Advance Genetics (8 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions