3.8 Control of Gene Expression Flashcards
Define gene mutation
change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide
When are errors in DNA most likely to occur?
DNA replication
What are the main types of gene mutations
Addition
-insertion of a base
-causes a frameshift to the right
-all subsequent codons are altered
-hence all subsequent amino acids may differ
-results in a different polypeptide being produced
Deletion
-removal of a base
-causes a frameshift to the left
-all subsequent codons are altered
-hence all subsequent amino acids may differ
-results in a different polypeptide being produced
Substitution
-a base in the DNA sequence is randomly swapped for a different base
-only change the amino acid for the triplet (group of three bases) in which the mutation occurs; it will not have a knock-on effect
-can take three forms:
-silent mutations – doesn’t alter amino acid sequence of the polypeptide as the genetic code is degenerate
-missense mutations – alters a single amino acid in the polypeptide chain (e.g. sickle cell anaemia)
-nonsense mutations – creates a premature stop codon = polypeptide chain produced to be incomplete - affects the final protein structure and function
Inversion
-usually occurs during crossing-over in meiosis
-DNA of a single gene is cut in two places
-cut portion is inverted 180° then rejoined to the same place within the gene
-leads to a large section of the gene being ‘backwards
-hence multiple amino acids are affected
-frequently result in a non-functional protein
-often harmful as the original gene can no longer be expressed from that chromosome
-effect may be lessened if the other chromosome in the pair carries a working gene
Duplication
-whole gene or section of a gene is duplicated so that two copies of the gene/section appear on the same chromosome
-original version of the gene remains intact hence not harmful
-overtime, the second copy can undergo mutations which enable it to develop new functions
-important source of evolutionary change
-alpha, beta and gamma haemoglobin genes evolved due to duplication mutations
Translocation
-gene is cut in two places
-section of the gene that is cut off attaches to a separate gene
-hence the cut gene is now non-functional due to having a section missing
-the gene that has gained the translocated section is likely to also be non-functional
-if section of a proto-oncogene is translocated onto a gene controlling cell division, it could boost expression and lead to tumours
-similarly, if a section of a tumour suppressor gene is translocated and the result is a faulty tumour suppressor gene, this could lead to the cell continuing replication when it contains faulty DNA
sme lesson 2
The Effect of Genetic Mutations
-mutations occur spontaneously and randomly during DNA replication
-DNA base sequence determines the sequence of amino acids that make up a protein
-hence mutations in a gene may lead to a change in the amino acid sequence coded for by the gene
-most mutations do not alter the polypeptide or only alter it slightly so that its structure or function is not changed
As the genetic code is degenerate (more than one triplet code codes for the same amino acid) some mutations will not cause a change in the amino acid sequence
Substitution mutations are the mutations that usually have a smaller effect on the resultant polypeptide
Some gene mutations change all base triplets downstream from (after) the mutation, this will result in a non-functional polypeptide
Insertion and deletion mutations result in a frameshift
Causes of mutations
The rate that mutations occur can be estimated as around one mutation per 100 000 genes per generation
Exposure to mutagenic agents can increase the rate of mutation, they include
High energy ionising radiation, such as alpha, beta or gamma radiation
Chemicals, such as nitrogen dioxide or benzopyrene from tobacco smoke
The effect of gene mutations on polypeptides
Most mutations do not alter the polypeptide or only alter it slightly so that its appearance or function is not changed
However, a small number of mutations code for a significantly altered polypeptide with a different shape
This may affect the ability of the protein to perform its function. For example:
If the shape of the active site on an enzyme changes, the substrate may no longer be able to bind to the active site
A structural protein (like collagen) may lose its strength if its shape changes
The effect of gene mutations on phenotype
Polypeptides / proteins affect the phenotype of an organism via specific cellular mechanisms
If a mutation causes a major alteration in a polypeptide then cellular mechanisms could be affected, which may impact the phenotype of the organism
For example, a mutation in the TYR gene in humans affects the structure of an enzyme that is needed for the production of the pigment melanin
The phenotype of the human is affected by the lack of melanin
Individuals with the mutation have albinism; very pale skin and hair
how transcription factors work
oestrogen as a TF
RNA interference
RNA Interference
RNA interference (RNAi) is a form of post-transcriptional modification which occurs in the cytoplasm
RNAi is sequence-specific silencing of gene expression and therefore can be very precise in silencing certain genes
Small interfering RNA
In eukaryotes and some prokaryotes, translation of the mRNA produced from target genes can be inhibited by RNA interference (RNAi)
Small, double-stranded RNA molecules called small interfering RNA (siRNA) bind to mRNA that has been transcribed from target genes (the genes to be ‘silenced’) as their base sequence is complementary
Each siRNA is attached to a protein complex which is able to breakdown the mRNA that has been transcribed from target genes (the genes to be ‘silenced’)
Therefore, the mRNA is unable to be translated into proteins
The RNA interference pathway
Double stranded RNA (dsRNA) is produced by RNA-dependent RNA polymerases (RDRs)
dsRNA is hydrolysed into smaller fragments, roughly 23 nucleotides long, called small interfering RNAs (siRNAs)
In the cytoplasm, siRNAs bind to protein complexes which use energy from ATP to separate the two strands of the siRNA
This exposes the nucleotide bases so they are able to pair with bases from an mRNA molecule
Once the target mRNA leaves the nucleus and enters the cytoplasm, single-stranded siRNA binds to the target mRNA through complementary base pairing
The mRNA molecule is cut into fragments by the enzyme/protein complex associated with the siRNA
Cut mRNA cannot be translated and therefore will not produce proteins
After the target mRNA has been cut up into fragments, the fragments are broken down into RNA nucleotides by enzymes
Therapeutic Application
siRNAs created against viral genetic material will signal for their degradation and stop the virus from using the host’s cellular machinery to replicate itself
siRNAs can be used in cancer treatment by targeting oncogenes that have been expressed or upregulated
This reduces the number of proteins produced that can lead to cancer or that maintain cancerous growth
