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Core Idea 2: Genetics and Inheritance - Coggle Diagram
Core Idea 2: Genetics and Inheritance
DNA Structure and Replication
Characteristics of DNA:
high capacity for info, stable, replicate accurately, capable of variation
Semi-conservative DNA replication: each parental strand used as template,
each of the two daughter DNA molecules consist of 1 parental DNA strand and 1 newly synthesised daughter DNA strand
Initiation
Topoisomerases
Single strand DNA-binding proteins
Helicases
Priming
cannot initiate synthesis of DNA strand on its own
Synthesis
Synthesis of daughter DNA in 5’ to 3’ direction (of daughter strand)
DNA polymerase
End Replication problem
Structure of DNA
Nucleotides
Double helix
LINK TO GOB
Bacteriophage replication
Organisation of the eukaryotic genome
DNA packaging
First level
10nm chromatin fibre
Second level
DNA further coiled and condensed involving histone H1 and linker DNA = 30nm chromatin fibre
Third level
Scaffold proteins condense 30nm chromatin fibre to form looped domains, which further coil to form 1400nm chromosome
Purpose: storage into small nucleus, protection from enzymes, prevent breakage during cell division, regulation of transcription
LINK TO EU GENE EXPRESSION
Regulation of transcription
Organisation of Eukaryotic Gene
Transcription unit: exons + introns
Regulatory sequences
Promoter
Control elements
Untranslated regions
Organisation of Eukaryotic Intergenic DNA
Repetitive DNA consists of telomeres and centromeres
Telomeres & End Replication Problem
tandem repeats of 5’-TTAGGG-3’
Functions of telomeres
Cap protects ends of linear chromosomes from degradation and being recognised as damaged DNA
Cap prevents chromosome tips from spontaneously fusing to ends of other chromosomes ⇒ stable
Acts as disposable DNA buffer against loss of genes
Regulates replicative cell senescence: the period when a cell withdraws permanently from cell cycle after reaching Hayflick limit
LINK TO MOLECULAR BASIS OF CANCER
activation of telomerase is the second step in the multistep progressions model of cancer, maintaining the length of the telomere such that the cell cannot reach its Hayflick limit, evading apoptosis
LINK TO DNA STRUCTURE AND REPLICATION
there is no free 3'OH end for DNA polymerase to extend from after the last RNA primer has been removed, resulting in the 5' end of the lagging strand being shorter
Centromeres
Site of assembly of kinetochore
Prevents replicated chromosomes from segregating randomly during cell division
LINK TO CELL DIVISION
centromeres divide in anaphase such that each daughter chromosome will have one centromere
Eukaryotic Gene Expression
Structure and role of RNA
tRNA
rRNA
Transcription
Initiation
Elongation
Termination
Post-transcriptional modification
Genetic code
Triplet code
Universal
Continuous and non-overlapping
Degenerate but unambiguous
Wobble base phenomenon at 3rd base
Start and stop codons
Translation
Initiation
Elongation
Termination
Post-translational modification
Control of Eukaryotic Gene Expression
Chromatin level
Histone modification
Histone Actylation
Histone deacetylation
DNA methylation
Transcriptional level
Control elements
Promoter
Proximal control elements
Distal control elements
Enhancers
Silencers
Transcription factors
Activators
Repressors
Competitive DNA binding
Masking activation surface
Block assembly of GTFs
Attracts histone deacetylase
Attracts histone methyltransferase
Post-transcriptional level
5’-methylguanosine cap
3’-poly (A) tail
Splicing
Translational level
RNA half-life
affected by
length of poly (A) tail
stabilising / destability sequence in 3’ UTR
Initiation of translation
Eukaryotic initiation factors
Translation repressors
Post-translation modifications
Biochemical modifications
Glycosylation
(reversible) Phosphorylation
Disqualified linkages
Attachment to ubiquitin
Removal of sequence of amino acids
Protein degradation
Link to Eukaryotic Cell Structure and Function
(Core Idea 1)
the role and function of the Golgi Apparatus
Gene mutations and chromosomal aberrations
Gene mutations
permanent change in nucleotide sequence of one gene
Base substitution
Missense mutation
Nonsense mutation
Silent mutation
Neutral mutation
Base insertion/deletion
Sickle-cell anemia
Substitution of thymine for adenine, AA glutamate (hydrophilic) changed to valine (hydrophobic), formation of a hydrophobic spot
LINK TO INHERITANCE
genotype affects phenotype
(Look at Q4b of BT)
alleles of a gene are transcribed to form different mRNA and translated into different polypeptide chains and proteins, which may affect metabolic pathways differently, leading to formation of different phenotypes
Chromosomal aberrations
Deletion
Inversion
Duplication
Translocation
LINK TO INHERITANCE
Result in diseased phenotype
(Look at BT Q4a)
Turner Syndrome
Klinefelter Syndrome
Down Syndrome
Molecular basis of cancer
Characteristics of cancer cells
High rate of cell division
Replicative immortality
No anchorage-dependent growth
Lack of contact inhibition
Angiogenesis (formation of new blood vessels)
Metastasis
Cell cycle
LINK TO CELL AND NUCLEAR DIVISION
cell cycle and process of interphase and mitosis
Interphase
G2 phase
G2 checkpoint
assessment of DNA replication
G1 phase
G1 checkpoint
assessment of cell growth
Leading to cancer
disruption of the checkpoints, leading to uncontrolled DNA replication, uncontrolled cell division
S phase
Mitosis
M checkpoint
assessment of mitosis
Cytokinesis
Oncogenes and
tumour suppressor genes
TSG usually halts cell cycle if dna is damaged, and recruits repair mechanisms
Loss of function requires both copies of genes to be mutated
P53: activate DNA repair proteins, arrest growth
Proto-oncogene and oncogene
Gain of function mutation requires only one copy of the mutated gene
Ras protein is a mutated protein kinase that has GTP constantly binding to the ras protein, leading to a hyperactive ras protein
Cancer progression
Multi-step process
Gradual accumulation of several mutations in cancer-critical genes in a single cell lineage
Leads to telomerase activation
Angiogenesis
Metastasis
LINK TO END REPLICATION PROBLEM
usually, the shortening of telomeres due to the end replication problem results in the cell being able to reach its Hayflick limit and undergo apoptosis, but telomerase action offsets this
Causative factors:
Polycyclic aromatic hydrocarbons, heterocyclic amines, ionising radiation causes free radicals of water to form, UV light is dna-damaging
Molecular techniques
PCR
Procedure
Annealing (54°C, 1 minute)
Elongation (72°C, 2 minutes)
Denaturation (95°C, 30s)
Limitations
Contamination
Require target DNA sequence
Amplify nucleotides only
Taq polymerase lack 5’ —> 3’ exonuclease activity
Less efficient for longer target sequences
LINK TO DNA REPLICATION
Taq polymerase catalyses the synthesis of phosphodiester bonds between the 3'OH end of the growing strand and the 5' phosphate group of an incoming dNTP, assembling incoming bases via CBP, hydrogen bonds
Gel Electrophoresis
Procedure
Preparation of gel with wells for DNA samples
Setting up for gel electrophoresis
Loading of DNA samples into well
Application of electric field
Staining of gel ito view separated DNA bands
Principles
Separates DNA molecules by size
Complex network of pores act as “molecular sieve”
DNA moves towards positive electrode
Use of DNA ladder
Shorter DNA fragments less impeded
LINK TO INHERITANCE, CANCER AND MUTATION
DNA profile of individuals to identify mutated allele
Leading to development of cancer
(Look at question 3 of BT)
Southern Blotting
Procedure
Blotting
Incubation with labelled probe
Detection of bound probe
Principles
dsDNA separated into ssDNA as H bonds disrupted
Prolonged period of low temperatures allows reforming of H bonds
Occur bretween any two ss nucleic acid chains (must be complementary)
LINK TO BIOLOGICAL EVOLUTION
extract the DNA from tissue samples -> PCR -> Gel E -> Southern/Northern Blotting used in Multiple Sequence Alignment (MSA)
Inheritance
Mendelian inheritance
Monohybrid inheritance: 3:1
Reciprocal cross
Test cross
Non-mendelian inheritance
Incomplete dominance: 1:2:1
Co-dominance; 1:2:1
Multiple alleles
Lethal genes: 2:1
Dihybrid inheritance
Mendal’s second law of independent assortment
Dihybrid cross: 9:3:3:1
Test cross with double heterozygous: 1:1:1:1
Non epistatic gene interactions: 9:3:3:1
Sex linkage
Males are homizygous
Normal female carrier x normal male => 1 normal female : 1 female carrier : 1 normal male : 1 affected male
X-linked diseases
Haemophilia
Red-green colour-blindness
Duchenne muscular dystrophy
Reciprocal cross
Traits of 2 parents are reversed
Yield on identical results, unlike autosomal traits: yield identical results
Pedigree analysis
Linked genes
Complete linkage (no crossing over): offspring 3:1, test cross 1:1
Incomplete linkage (crossing over): 4 phenotypes, majority 2 parental
Chromosome mapping: Distance between 2 genes on a chromosome modelled by % of individuals showing recombination
Epistasis
Recessive epistasis
9:3:4 with double heterozygous cross
2 recessive alleles at epistatic gene locus inhibit effect of either allele at hypostatic gene locus
Dominant epistasis
1 dominant allele at the epistatic gene locus inhibit effect of either allele at hypostatic gene locus
12:3:1 with double heterozygous cross
Duplicate recessive epistasis
2 recessive alleles at either gene locus inhibit effect of dominant allele at the other gene locus
9:7 with double heterozygous cross
Continuous variation
Polygenic inheritance: Genes act in an additive manner, with combined effects producing many phenotypic varieties
Genetic variation due to
Random fertilisation
Genetics of Bacteria
Bacteria structure and morphology
Cell wall
Peptidoglycan
LINK TO ETA (action of antibiotics)
natural penicillin is only affective against gram-positive bacteria as gram-negative bacteria are impermeable to the antibiotic
Gram-positive: Thick
Gram-negative Thin
Cell membrane
Flagellum
Pilus
Ribosomes (smaller than eukaryotic)
Endosymbiont theory: mitochondria and plastids of eukaryotes arose due to symbiosis
Evidence: Replication of mitochondria and chloroplasts are similar to that of prokaryotes
Ribosomes of mitochondria are similar to prokaryotic ribosomes
Mitochondria and chloroplasts contain circular DNA, not associated with histones, looking like bateria
Prokaryotic, lack true nucleus and membrane-bound organelles
Prokaryotic genome
Singular circular dsDNA
Genes are grouped into operons, multiple genes come under control of same promoter
Lack introns, do not need splicing
Plasmids: small circular ds extrachromosomal DNA, possess Ori, and beneficial genes
Gene transfer
Vertical
Binary fission
Horizontal
Transformation:
Donor cell lyses to release naked DNA fragments
Competent cell takes up fragments via competence factor
Homologous recombination
Transduction: Accidental incorporation of random fragment of DNA by bacteriophages
Homologous recombination
Generalised
Specialised: DNA adjacent to prophage
Conjugation:
F+ cell uses sex pilus to attach to F- cell
F plasmid move via temporary cytoplasmic mating bridge
LINK TO BE (variation for natural selection to act on)
Look at Q4(b) of BT
Prokaryotic gene expression
Same as EGE, except
RNA pol recognition site (5’-TTGACA-3’ for non template strand) 35bp upstream of TSS
Pribnow box/RNA pol binding site (5’- TATAAT-3’ for non template strand) 10bp upstream of TSS
5’ UTR: give rise to Shine-Dalgarno
Rho-dependent/independent termination
Differences btw pro & eu gene expression
Control of prokaryotic gene expression
Transcriptional control
Operon
Promoter
Operator
Structural genes
Regulatory genes
Inducible: Normally not transcribed and need to be turned on by the substrate of the enzyme which the structural genes code for
Eg. lac operon
Repressible: Normally transcribed and need to be turned off by the product of the pathway
Eg. trp operon
Positive control
Negative control
Post-translational control: Adding functional groups and cleavage of proteins
Cell and Nuclear Division
Mitosis
Prophase
Anaphase
Metaphase
Telophase
Significance
Maintain genetic stability
Allows for growth, repair and regeneration
Allows for asexual reproduction
Meiosis
Meiosis I
Metaphase I
Prophase I
Crossing over of sister chromatids
Anaphase I
Random segregation of paired alleles on homologous chromosomes
Independent assortment of pairs of alleles
Telophase I
Meiosis II
Prophase II
Metaphase II
Anaphase II
Telophase II
Significance
Increase genetic variation of gametes
New allele combinations
Independent assortment
Crossing over
Allows for sexual reproduction
LINK TO GENE AND CHROMOSOMAL MUTATIONS
Failure of non-disjunction,
allopolyploidy, autopolyploidy
The Cell Cycle
Mitosis
Cytokinesis
Interphase
Genetics of Viruses
Viruses violates the cell theory (obligate intracellular parasites)
Unable to carry out metabolic processes eg. protein synthesis
Lack protoplasm or organelles
Lack the necessary molecular machinery to replicate itself
Rely on host cells for replication
LINK TO CELL THEORY
Cells are the most basic unit of life - viruses are acellular
All cells come from pre-existing cells - viruses cannot replicate unless they have entered a suitable host cell
All organisms are made up of cells
Testing of cell theory
observe cell using microscope
size of cells
(Link to GOB, differences between eukaryotic and prokaryotic cell)
cell and nuclear division
(Link to Cell division) observe if mitosis and meiosis takes place
Bacteriophage
T4 phage
Components
dsDNA
Capsid
Tail (tail sheath, tail fibre and base plate)
Tail fibre attach to specific receptor sites, tail sheath contracts via conformational changes, pierces membrane
DNA is extruded into host cell through tail tube
T4 phage lyse host cell via lysozyme, digesting bacterial cell wall
LINK TO DNA replication & gene expression
host cell genome is degraded to be used as raw materials for replication of phage genome by host cell DNA polymerase, host cell RNA polymerase used to synthesise viral proteins
Lambda phage
Components
dsDNA
Capsid
5’ terminus of each DNA strand is a ss tail of 12 nucleotides long for prophage formation
Non-contractile tail fibre
Genome circularises, insert into specific site in bacterial chromosome (prophase insertion site)
When there is environmental trigger, the virus switches from lysogenic to lytic cycle
Animal viruses (enveloped)
Influenza
Components
8 segments of -ve sense ss RNA, must be converted to +ve sense for translation
HA: binds to sialic acid containing receptors
NA : cleaves sialic acid containing receptors for budding
LINK TO ENZYMES & PROTEINS
Inhibition of viral enzymes and proteins to prevent viral infection
RNA-dependent RNA polymerase (replicase) for replication and transcription
Receptor-mediated endocytosis in endosome
Fusion of endosome with lysosome, ph drop, conformational change, viral envelope and endosome membrane fuse, release viral segments
LINK TO GENE EXPRESSION
viral replicase copies (-) sense RNA into complementary (+) sense RNAs for synthesis of viral protein, viral nucleic acid, enzymes, matrix and capsomeres proteins
LINK TO CELL SURFACE MEMBRANE
Process of endocytosis and exocytosis
HIV
Components
gp120, gp41
Reverse transcriptase, integrase, protease
2 identical ss RNA
Gp120 bind to CD4, undergo conformation change, bind to co-receptor CXCR4. Gp41 pulls the virus closer to cell, co receptor facilitates entry. HIV envelope fuses with host cell membrane
LINK TO gene expression
Virus uses host cell mechanism to synthesize viral genome and proteins
Integration of viral DNA into genetic material of host, forming provirus
Forms provirus
LINK TO CORE IDEA 1: HOST PHOSPHOLIPID BILAYER
Fluid Mosaic Model
phospholipids are held together by weak hydrophobic interactions, can move laterally
proteins are randomly distributed throughout the bilayer, both layers are asymmetric
glycoproteins are involved in cell-to-cell adhesion and cell-to-cell communication (surface antigens like HA and gp120)
LINK TO ETA
viral infection
Influenza
targets the epithelial cells of the respiratory tract
NA cleaves the sialic acid residues in mucus, facilitating infection
excessive budding depletes the cell membrane
HIV
infects T-helper cells, macrophages (APCs) with CD4 receptors
prevents adaptive immune system from being activated, impairs innate immune response -> vulnerable to opportunistic infections
formation of provirus in host cell genome establishes latent infection, evade detection from cytotoxic T cells, continue to reproduce
Antigenic drift and shift
Drift: Accumulation of mutations, slight change in 3D conformation of antigens
Influenza virus has no complementary strand, thus no proofreading
Viral polymerases prone to error
LINK TO ETA
pre-existing immunity to the modified surface proteins
Link to adaptive immune system and action of antibodies
Production of memory B cells and secretion of antibodies to target pathogens
Action of antibodies
Opsonisation
Activation of complement system
Neutralisation
Shift: Sudden change in antigenicity due to reassortment of virus genome with another virus genome from co-infection. New combinations of viral proteins
LINK TO MUTATIONS AND GENETIC VARIATION
LINK TO ETA
no immunity to the modified surface proteins