Mutations And Gene Expression Flashcards
Mutation
Random change in base sequence of DNA
The order of DNA bases in gene determines
The sequence of amino acids in a particular polypeptide
If a mutation occurs in the gene
The sequence of amino in the polypeptide that it codes for could be changed
Substitution mutation
One or more bases are swapped for one another
Deletion mutation
One or more bases are removed
Addition mutation
One or more bases are added/ inserted
Duplication mutation
One or more bases are repeated
Inversion mutation
A sequence of bases is reserved
Translocation mutation
A sequence of baes is moved from one location in th genome to another
This could be movement within the same chromosome or movement to a different chromosome
Silent mutation
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If a mutation doesn’t cause a change in the sequence of amino acids
As the genetic code is degenerate, some amino acids are coded for by more than one triplet code
Which three mutations almost always cause a change in the amin acid sequence of a polypeptide
Addition
Duplication
Deletions
Frame shift
A shift in the base triplets that follow the mutation so that the triplet code is read in a different way
The base triplets that follow on from the mutation are said to be downstream
What in a mutation would bring transcription to a permanent halt
If. Stop codon is introduced
Mutagenic agents
Increase the rate of mutations
Examples of mutagenic agents
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Ultraviolet radiation
Ionising radiation
Some chemicals
Some viruses
Mutagenic agents
Acting as a base
Chemicals called base analogs can substitute for a base during DNA replication, changing the base sequence in the new DNA
Mutagenic agents
Acting as a base
Example
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5- bromouracil
Substitutes for thymine
Incorporates with the DNA and is most likely to pair with adenine however can spontaneously shift into another isomer which pairs with guanine
If thi happens during DNA replication, a guanine will be inserted as the opposite base analog, and so in the next DNA replication , the guanine will pair with a cytosine
Mutagenic agents
Altering bases
Some chemicals can delete or alter bases
Mutagenic agents
Altering bases
Example
Alkylating agents
Add an alkyl group to guanine
Changes its structure so that it pairs with thymine instead of cytosine
Mutagenic agents
Changing the structure of DNA
Some types of radiation can change the structure of DNA, which causes problems during DNA replication
Mutagenic agents
Changing the structure of DNA
Example
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UV radiation
Cause adjacent thymine bases to pair up together
This alters the structure of DNA and consequently inhibit polymerases and stop replication
Unprepared dimers are usage in
Pyramiding dimers awe the primary cause of melanomas in humans
Stem cells
Unspecialised cells that have not differentiated and so may specialise to become any cell type and can undergo mitosis
Summary of how cells become specialised through gene expression
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Genes expresses -> mRNA transcribed and translated into proteins -> proteins modify the cell -> cell becomes specialised for a particular function
Genes switched off -> mRNA not transcribed or translates -> proteins not produced
4 types of stem cells
Totipotent
Pluripotent
Multi potent
Unipotent
Totipotent stem cells
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Found in the early embryo and can differentiate into any type of cell
Since all body cells are formed from a zygote, the zygote is totipotent
As the zygote divides and matures, its cells develop into slightly more specialised cells called pluripotent stem cells
Pluripotent stem cells
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Found in embryos and can differentiate i to almost any type of cell
Examples= embryonic stem stem cels and foetal stem cells
Multi potent stem cells
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Found in adults and can differentiate into a limited number of specialised cells
They usually develop into cells of a particular type
Eg stem cells inn the bone marrow can produce any type of blood cells
Examples= adult stem cells, umbilical cord, blood stem cells
Unipotent stem cells
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Can only differentiate into a single type of cell
Derived from multi potent stem cells and are made in adult tissue
Cells used for treating human disorder
Pluripotent
Uses of pluripotent cells
Cells can be used to regrow tissues that have been damaged in some way either by accident or s a result of disease
Possible future uses of stem cells
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Spinal cord injuries- stem cells could replace damaged nerve tissue
Heart disease and damage from heart attacks- stem cells could be used to replace damaged heart tissue
Bladder conditions= stem cells could be used to grow whole bladder, which are then implanted in patients to replace diseased ones
Respiratory diseases= donated windpipes can be stripped down to their simple collagen structure and then covered with tissue generated by stem cells, this can then be transplanted into patient s
Organ transplants= organs could be grown from stem cells to provide new organs
Cardiomyocytes
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Heart muscle cells
Used to be thought that they couldn’t divide and replicate which would be a problem if heart became damaged
Recently reader has shows that heart does have some regenerative capabilities
Some think that old or damaged cardiomycytes can be replaced by new ones derived from a small supply of unipotent stem cels in the heart
Some think think its a constantly occurring process but don’t know how fast it is
Some think its a very slow process and some cardiomyocytes are never replaced
Others think it’s occurring quickly and cardiomyocytes are replaced several times in a life time
Induced pluripotent stem cells
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A type of pluripotent cell that are produced from unipotent stem cells which could be almost any body cell
The unipotent body cells are then genetically altered in an laboratory to make them acquire characteristic of embryonic stem cells, which a re a type of pluripotent cell
This occurs because the adult cells are made to express a series of transcription factors that are normally associated with pluripotent stem cells
Transcription factors are proteins that control whether or not genes are transcribed
The TF cause the adult body cells to express genes that are associated with pluripotency
Useful feature of nudged pluripotent stem cells
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They are capable of self renewal
This means they can potentially divide infinitely to provide a limitless supply
They could replace embryonic stem cells in medical research and treatment and therefore overcome some of the ethical issues surrounding using embryos in stem cell research
Stem cells ethical issues
Obtaining stem cells using IVF raises ethical issues because the procedure results in the destruction of an embryo that become aa foetus if placed in a womb
Currently only allowed in the uk under licensed and specified conditions
The rates of gene expression can be controlled through
regulation of transcription and/or translation
Three factors affecting the rate of gene expression
Transcription factors - Ffestiniog th rate of transcription
Epigenetics- affect the rate of transcription
RNA interference (RNAi) - affects the rate of translation
What is a transcription factor
Transcription is when a gene is copied from DNA into mRNA, using the enzyme RNA polymerase
For transcription to occur, the g ene is switched on by specific protein molecules called transcription factors
In eukaryotes transcription factors move from the cytoplasm to the nucleus, where they bind to specific DNA sites called promoters
Promotes are found near the start of their target genes- the genes they control the expression of
Transcription factors control expression by controlling the rate of transcription
Activators transcription factors
Stimulate or increase rate of transcription
eg. They help RNA polymerase to bind to the start of the target gene and activate transcription
Repressors - transcription factors
Inhibit or decrease rate of transcription
Eg they bind to start of the target gene, preventing RNA polymerase from binding, therefore stopping transcription
Example of a transcription factor= oestrogen receptor
Steroid hormones like oestrogen can switch on a gene and therefore start transcription
Oestrogen is lipid soluble so can diffuse easily through the phospholipid bilayer of the ell surface membrane
Once inside the cell, oestrogen binds to a transcription factor called an oestrogen receptor which is complimentary shaped
This forms an oestrogen-oestrogen receptor complex
When it binds, the oestrogen changes the shape of the dNA binding site on the transcription factor, so it can now bind to DNA at specific promoter sequences upstream of the gene
The complex enters the nucleus of the cell through a nuclear pore and binds to specific base sequences of the DNA
Epigenetic control of gene expression
Involves inheritable changes in gene function , without changes to the base sequence of DNA
Changes caused by changes in the environment that alter transcription through attachment or removal of chemical groups ( epibenthic markers) to or from DNA or histone proteins
Two methods to inhibit transcription
Epigenetic
Increased methylation of DNA- CH3 group
Decreased acetylation of associated histones- COCH3 group
Increased methylation of DNA
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When a methyl group ( epigenetic marker) is attached to the DNA coding for a gene
The group always attached to a CpG site, which is where a cytosine and gamine base are next to each other in ther DN A
Increased methylation changes the DNA structure so that transcriptional factors cant bind so transcription cant occur and gene is not expressed/ switched off
Decreased acetylation of histones
3
Histones can. Be epigentically modified by the addition or removal of acetyl groups ( epigenetic marker)
When histones are acetylated, the chromatin is less condensed. Transcription factors can accès the DNA so slow in transcription
When acetyl groups are removed from the histones, the chromatin becomes highly condensed and genes i n the DNA cant be transcribed because transcription factors cant access the dNA
Treating diseases with epigenetic therapy
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Many diseases, such as cancer, are triggered by epigenetic changes that cause certain genes to be activated or silenced.
As epigenetic changed are reversible, they make good targets for new drugs to combat diseases they cause.
Increased DNA methylation can lead to genes. Being switched off
Drug that stop DNA methylation can sometimes be used to treat diseases
The problem with developing drugs to counteract epigenetic changes is that these changes take place normally in a lot of cells , it’s therefore important to make the drugs as specific as possible
What is RNAi
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RNA interference affects gene expression
RNAi is where small, double stranded RNA molecules stop mRNA from target genes being translated into proteins in eukaryotic cells
A similar process too RNAi ca also occur in some prokaryotes
The molecules involved in RNAi are called small interfering RNA (siRNA) and microRNA (miRNA)
These molecules are non coding RNA
SiRNA
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Once mRNA has been transcribed, it leaves the nucleus for the cytoplasm
In the cytoplasm, double stranded siRNA associates with several proteins and unwinds
One of the resulting singe strands of siRNA is selected and the other strand is broken down
The single strand of siRNA binds to the target mRNA because they have a base sequence which is complimentary
The proteins associated with the siRNA cut the mRNA into fragments so it can no longer be translated
The proteins and siRNA complex is called and RNA-induced silencing complex
MiRNA in plants
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Similar process to siRNA
Like siRNA, the base sequence of plant miRNA is complimentary to the target mRNA sequence and therefore binding occurs and the mRNA is cut up and broken down
It’s production is similar too that of mammalian miRNA
MiRNA in mammals
MiRNA isn’t fully complimentary to the target mRNA which makes it less specific than siRNA and so it can target more than one mRNA molecule
When miRNA is first transcribed, it exists as a long, folded strand
It is processed into a double strand and then into two single strands by enzymes in the cytoplasm
Like siRNA, one strand associates with proteins and binds to. Target mRNA in the cytoplasm
Instead of the proteins associated with miRNA cutting mRNA into fragments, the miRNA-protein complex physically blocks translation of the target mRNA
The mRNA is then moved into a processing body,where it can either be stored or broken down
When its stored, it can be returned and translated at another time
Small nuclear RNAs
Operate with nuclei, where they are tightly bound to proteins to form small nuclear ribonuclearproteins
SnRNPs
Control the splicing of pre-mRNA
Evaluating data on phenotypes
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The phenotype of an organism is the result of an organisms genotype and the interactions of the genotype with the environment
It’s not always clear how much a phenotype is influenced by genetics or environment
Twin studies
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Studies of genetically identical twins are extremely useful when trying to determine what is due to genetics and what is due to environment
Any dfferences in phenotypes must be due to environment
Very similar characteristics= most likely due to genetics
Very different characteristics= most likely due to environment
What is a tumour
If a mutation occurs in a gene that control the rate of cell division (mitosis), it can cause uncontrolled cell division
If a cell divides uncontrollably the result is a tumour- a mass of abnormal cells
Tumour that invade and destroy surrounding tissue are called cancers
2 types of tumours
Malignant= cancerous
Benign= not cancerous
Malignant v benign
Size
Benign= can grow to a large size
Malignant= can grow to a large size
Malignant v benign
Speed of growth
benign= grow very slowly
Malignant= grow rapidly
Malignant v benign
Nucleus
Benign- cell nucleus has a relatively normal appearance
Malignant= cell nucleus is often larger and appears darker due to an abundance of DNA
Malignant v benign
Differentiated
Benign= cells are often well differentiated (specialised)
Malignant= cells becomes de-differentiated (unspecialised)
Malignant v benign
Adhesion molecules
Benign= cells produce adhesion molecules that make them stick together and so they remain within the tissue from which they arise= primary tumours
Malignant= cells do not produce adhesion molecule and so they tend to spread to other regions of the body, a process called metastasis, forming secondary tumours
Malignant v benign
Surrounded by
Benign= tumours are surrounded by a capsule of dense tissue and so remain as a compact structure
Malignant= tumours are not surrounded by a capsule and so can grow finger like projections into the surrounding tissue
Malignant v benign
Threat
Benign= much less likely to be life-threatening but can disrupt functioning of a vital organism
,alignant= more likely to be life threatening, as abnormal tumour tissue replaces normal tissue
Malignant v benign
Effect on body
Benign= localised effects on the body
Malignant= often have systematic (whole body) effects such as weight loss and fatigue
Malignant v benign
Removal
Benign= can usually be removed by surgery alone
Malignant= removal usually involves radiotherapy and/or chemotherapy as well as surgery
Malignant v benign
Reoccurrence
Benign= rarely reoccur after treatment
Malignant= more frequently reoccur after treatment
Cancer and the genetic control of cell division
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DNA analysis of tumours has shown that, in general, cancer cells are derived from a single mutant cell
The initial mutation causes uncontrolled mitosis in this cell
Later, a further mutation in one of the descendant cells leads to other changes that cause subsequent cells to be different from normal in growth and appearance
Two main types of genes that play a role in cancer
Tumour suppressor genes
Proto-oncogenes
Tumour suppressor genes
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When functioning normally, these genes slow cell division by producing proteins that stop cells dividing or chase programmed cell death (apoptosis)
If a mutation occurs in a tumour suppressor gene, the gene will be inactivated
The protein i codes for is not produced, and the cells divide uncontrollably, the rate of division increases
Oncogenes
Most oncogenes are mutation of proto-oncogenes
When functioning normally, proto-oncogenes stimulate cell division by producing proteins that makes cells divide
If a mutation occurs in a proto-oncogene, the gene can become overactive
This stimulates the cells to divide uncontrollably (the rate of division increases) resulting in a tumour
Abnormal methylation of tumour suppressor genes
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Abnormal methylation of DNA is common in the development of a variety of tumours
The most common abnormality is hypermethylation (increased methylation) but another form is hypomethylation (reduced methylation)
Hypermethylation tumour suppressor gene
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Occurs in a specific region (promoter region) of tumour suppressor genes
This leads to the tumour suppressor gene being inactivated
As a result, transcription of the promoter regions of tumour suppressor genes is inhibited
The tumour suppressor gene is therefore silenced (switched off)
As the tumour suppressor gene normally slows the rate of cell division, its inactivation leads to increased cell division and the formation of a tumour
Hypomethylation oncogene
Hypomethylation of proto- oncogenes causes them to act as oncogenes
so increasing the production of proteins that encourage cell division
This stimulates cells to divide uncontrollably which causes the formation o tumours
Role of oestrogen in breast cancer
Oestrogen plays a role in regulating menstrual cycle
After menopause a woman’s risk of developing breast cancer increases, thought to be due to increased oestrogen concentrations produced by fat cells in the breast
These locally produced oestrogen hormones appear to trigger breast cancer in post menopausal women
Once a tumour has developed, it further increases oestrogen concentration which therefore leads to increased development of the tumour
It also appears that white blood cells that are drawn to the tumour, increase oestrogen production too
This leads to even greater development of the tumour
2 types of risk factors for cancer
- Genetic= spoken cancers are linked with specific inherited alleles
- Environmental= exposure to radiation, lifestyle choices such as smoking, increased alcohol consumption, high fat diet
Preventing cancer
If a specific cancer-causing mutation is known, then it is possible to screen for mutation in the persons DNA.
Knowing about this increased risk, means that preventative steps can be taken to reduce it
Knowing about specific mutations also means that more sensitive tests can be developed, which can lead to earlier and more accurate diagnoses
Treati g and curing cancer
Treatment for cancer can be different for different mutations, so knowing how specific mutations actually cause cancer can be very useful for developing drugs to effectively target them
Some cancer mutations require more aggressive treatment than others, so understanding how the mutation that causes them works can help produce the best treatment plan
