Translation, Genetic Code, Gene Regulation & Expression Flashcards
(25 cards)
is genetic code overlapping?
no
because single base mutations only ever affect 1 a.a
The genetic code is universal, although some organisms/organelles have slight variations
examples?
- mitochondria
- some flatworms, roundworms and tapeworms
- some protozoa
- candida sp of yeast (CUG → Ser)
- Bacteria & Archaèa (CUG & UUG also commonly used as start codons)
translation steps
- initiation -> binding of small subunit & progression up to start codon (AUG)
- elongation
- termination
mutation
due to changes in DNA base seq
transition vs. transversion
mutations
- transitions: interchanges of 2-ring purines
(A G) / of 1-ring pyrimidines (C T)
-> ∴ involve bases of similar shape - transversions: interchanges of purine for pyrimidine bases
-> ∴ involve exchange of 1-ring and 2-ring structures
types of mutations introduced by single base substitutions
- silent
- neutral
- mis-sense
- nonsense
examples of polyphenism
gene expression
- Daphnia pulex -> can grow horn (armour) in prescence of predator (external stimuli)
- Myzus persicae -> single mother can produce female baby with no wings (apterous) & female baby with wings (alate)
remodelling proteins
- physically push apart nucleosomes
- to allow RNA pol. 2 & basal factors to bind to promoter
nucleosomes
repeating units in chromatin
operon
bacterial gene expression
- group of genes with related functions clustered together
- operon has 1 promoter
- all genes in operon transcribed together
telomere
chromosome structure
- highly repetitive DNA that allow ends of chromosomes to be replicated
- also protects ends of chromosomes being mistaken as broken
origin of replication
chromosome structure
- special seq where duplication of DNA begins
- each chromosome will have many origins
mitosis stages
- prophase -> chromosomes become visible
- metaphase: chromosomes align at equator of cell
- anaphase: chromosomes separate
- telophase: 2 nuclei form
RNAi
RNA interference
mechanism of silencing gene expression
RNAi gene silencing in natural systems
how does ↑ no. of copies of gene lead to ↓ mRNA?
- 1998 - Andrew Fire & Craig Mello working on gene expression in nematode C. elegans
- they found that when they injected sense & artisense RNA together (‘double stranded’ RNA or dsRNA) …
- they were able to ↓ expression of protein involved in movement
in a series of experiments, what did Fire & Mello deduce?
- dsRNA silences genes by ↓ levels of mRNA with matching nucleotide seq.s
- RNAi is specific for gene with code that matches RNA injected
- RNAi can spread between cells & even be inherited
Why do organisms contain all the elements of the RNAi pathway, such as ‘dicer’ ?
RNAi in nature
RNAi may represent a primitive immune system that could protect organisms against exogenous genetic elements eg. transposons / viruses whose lifecycle includes a dsRNA stage
- viral dsRNA infects organism
- host RNAi machinery breaks apart dsRNA
- host siRNAs spread throughout organism so it’s resistant to virus next time it’s infected
can viruses ‘fight back’ ?
In ongoing ‘arms race’ between host & pathogen, both plant & animal viruses have evolved proteins that suppress gene silencing (eg. p19 protein)
Does RNAi gene silencing work in nature?
- MicroRNAs which act like RNAi…
- have been shown to be key regulators in many biological processes eg. development, cell birth & death, & cancer
is there clinical potential for RNAi ?
- RNAi, with its potential to specifically target gene expression, has potential to fight almost every disease imaginable
- how close are we to seeing RNAi transform medicine? -> example: Macular degeneration
- also Hepatitis C -> In 2002 researchers at Stanford Uni announced their RNAi treatment had controlled Hepatitis C virus in lab mice
-
macular degeneration
example of RNAi in medicine
- protein called VEGF (Vascular Endothelial Growth Factor) promotes blood vessel growth that can destroy vision
- RNAi can be delivered directly to diseased tissue through injection
- 1st clinical trial of 24 patients in 2004 had promising results, with 25% of patients showing significantly clearer vision
BUT STEM CELL TRANSPLANTS ARE MORE SUCCESSFUL
Nature Biotechnology June 2007
clinical potential of RNAi
Australia tackles ‘bird’ (avian) flu using RNAi
- Therapeutic -> deliver RNAi in drinking water, boost innate immune system
- Prophylactic -> use transgenes (stable genetic insertion) to introduce permanent protection to influenza virus
can RNAi be used as new contraception?
(alternate to the pill & its side effects)
clinical potential of RNAi
- in fertilisation, sperm binds to specific protein ZP3, before acrosome reaction which leads to egg being fertilised
- so if we can block production of ZP3 => no fertilisation
- so RNAi ZP3 encoding gene => failure in fertilisation :)
