Control of gene expression and epigenetics Flashcards
What are the 3 possible consequences of a substitution mutation?
- premature stop codon
- different amino acid coded for
- no change due to degeneracy of genetic code (silent)
Why do addition/deletion mutations have a greater effect than substitution mutations?
They result in a frameshift - when the genetic code is shifted left/right by one letter so the gene is read in the wrong 3 base groups, so all the amino acids coded for will be different - this will lead to the production of a non-functional protein which will largely effect the phenotype
What are the other types of mutations?
- addition
- duplication - one or more bases are repeated resulting in a frameshift
- inversion - the order of a group of bases is reversed
- translocation - a base sequence on one chromosome is separated from one chromosome and inserted into another chromosome
What are the causes of mutations?
- high energy ionising radiation eg. X-rays/uv light - disrupt the structure of DNA
- chemicals eg. asbestos - alter the structure of DNA and interfere with transcription
What are mutagenic agents?
Factors that increase the rate of mutations
How might mutations be useful to an organism?
they may produce the genetic diversity needed for natural selection - this will give an organism advantageous alleles which make it more likely to survive in its environment, outcompete others and pass on the alleles to offspring
In humans, body cells are all derived from mitotic divisions of the zygote therefore all contain the same genes. So why can’t all cells produce the same hormones?
Although all cells contain the same genes, only certain genes are expressed (switched on) in a cell at a certain time
What are totipotent cells?
cells such as fertilised eggs which can mature into any kind of body cell
How do cells become specialised?
Because only part of the DNA of a cell is translated into proteins, and the cell will therefore only produce proteins required to carry out its specialised function. Therefore only some of the genes are expressed
What are the ways in which genes are prevented from expressing themselves?
- preventing transcription and therefore preventing the production of mRNA
- preventing translation
Why can xylem cells not specialise into other cells?
Because once they are matured, they lose their nuclei - the nucleus contains the genes and therefore without these genes the cells cannot develop into other cells
What are stem cells?
undifferentiated dividing cells that can divide to form an identical copy of themselves - they can differentiate into any type of cell
Where do stem cells originate from?
- embryonic stem cells
- umbilical cord blood stem cells
- placental stem cells
- adult stem cells
What are the types of stem cells?
- totipotent stem cells - found in the early embryo and can differentiate into any type of cell, as the zygote divides and matures cells become slightly more specialised into:
- pluripotent stem cells - found in embryos and can differentiate into almost every type of cell, but not all
- multipotent stem cells - found in adults and can differentiate into a limited number of specialised cells eg. stem cells in bone marrow
- unipotent stem cells - can only differentiate into a single type of cell
What are induced pluripotent stem cells?
- a type of pluripotent cell that is produced from adult somatic cells using protein transcription factors, the unipotent cell may be any type of body cell which is genetically altered in a lab to acquire characteristics of embryonic stem cells by switching on genes that were switched off during specialisation
Why are iPS cells important for the future?
they can divide to provide a limitless supply, therefore can replace embryonic stem cells in medical research and treatment, so overcomes ethical issues
How can pluripotent stem cells be used in treating human disorders?
- regrow damaged tissues eg. skin grafts
- blood cells for leukemia
- nerve cells for Parkinson’s disease
What are totipotent cells?
cells that can mature into any type of body cell - during development, they will only translate part of their DNA resulting in cell specialisation
What is a transcriptional factor?
a protein necessary to initiate transcription, this is what allows cells to become specialised because only certain regions of DNA will be transcripted
How does oestrogen act as a transcription factor?
- oestrogen is a small, lipid-soluble molecule and therefore can easily diffuse into the cytoplasm through the phospholipid bilayer
- oestrogen enters the cell and binds to the complementary binding site on the transcription factor
- when oestrogen binds, it changes the shape of the DNA binding site, releasing the inhibitor which causes the DNA binding site to change shape and becomes complementary to the DNA promoter
- transcription factor enters the nucleus through nuclear pores and binds to DNA at the promoter, stimulating RNA polymerase and therefore transcription
What is epigenetics?
involves hertiable changes in gene function, without changes to the base sequence of DNA. These changes are caused by changes in the environment that inhibit transcription by:
- increased methylation of DNA
- decreased acetylation of histones
What is the epigenome?
all of the chemical tags that are added to the DNA histones which determines the shape of the DNA-histone complex
How (simply) and why does the epigenome change?
The chemical tags can respond to changes in the environment - this adjusts how tightly packed the DNA is - tightly packed DNA cannot be accessed to be transcribed so this switches the gene off, whereas loosely packed DNA exposes DNA so it can easily be transcribed and the gene will be switched on
How does decreased acetylation of associated histones affect the gene expression?
- acetyl coA donates a negatively charged acetyl group to the histones which attaches to the histone tails
- decreasing acetylation increases the positive charges on histones which increases their attraction to the negatively charged phosphate group in DNA
- this leads to a stronger association between DNA and histones, meaning the DNA is not accessible to transcription factors
- this means mRNA production cannot be stimulated so the gene is switched off
How does increased methylation of DNA affect the gene expression?
- methyl group is added to the cytosine bases on DNA
- this will inhibit transcription because it blocks binding sites at the promoter on DNA, preventing transcriptional factors from binding
- attracts proteins which cause the DNA-histone complex to condense and become inaccessible to transcription factors
What effects do acetylation and methylation have on gene expression?
methylation masks. acetylation allows
What conditions are needed for a gene to be active?
- acetylated histones
- unmethylated
- not condensed DNA-histone complex
How can epigenetic therapy be used to treat diseases?
- using drugs to inhibit enzymes that cause DNA methylation - reactivates silenced genes
- develop diagnostic tests that can identify the level of DNA methylation and histone acetylation at an early stage
What is the effect of RNA interference on gene expression?
- an enzyme cuts large double-stranded molecules of RNA into smaller sections called siRNA (small interfering RNA)
- one of the siRNA strands combines with an enzyme
- the siRNA molecule guides the enzyme to an mRNA molecule through complementary base pairing
- the enzyme cleaves mRNA into smaller pieces, meaning that it is no longer able to be translated into a polypeptide, and therefore the gene is switched off
How can siRNA be used to treat diseases?
- can be used to silence mutated genes that may cause disease by cleaving the mRNA that the harmful protein is produced from
What is the difference between benign and malignant tumours?
benign = smaller, well-differentiated, non-cancerous - they have no metastasis and are surrounded by a capsule so cannot spread around the body
malignant = larger, poorly-differentiated and cancerous - they have metastasis and no capsule so can spread around the body
What is a tumour?
a mass of cells that are a result of rapid, uncontrollable cell division
What is metastasis?
when cancerous cells spread elsewhere in capillaries/bloodstream
How do tumours develop and how can this lead to metastasis?
- mutated cell continually divides uncontrollably as it does not recognise signals to stop which causes a small primary tumour to develop
- as the tumour mass grows, blood and lymph vessels grow which provides more nutrients for further growth
- a few cells break away into a capillary which allows the cancerous cells to spread elsewhere (metastasis)
- cells are carried in the blood to new organs where they leave the capillaries
- start of a metastatic tumour when these cells divide continuously, producing a secondary tumour
- some cells can also break off into lymph glands to form gland tumours
What can unipotent stem cells be used to make?
cardiomyocytes - heart muscle cells
How do transcription factors cause specialisation?
without the binding of a transcription factor, the gene will remain inactive so the protein will not be translated - only certain genes will be switched on
What are the active and silent regions of DNA called?
active = euchromatin
silent = heterochromatin
How might tumours develop (reasons)?
- gene mutations in the tumour suppressor genes and/or oncogenes
- abnormal methylation of tumour suppressor genes and/or oncogenes
- increased oestrogen concentrations affecting transcription
What are proto-oncogenes and oncogenes?
- proto-oncogenes create proteins which are involved in the initiation of DNA replication and mitosis
- oncogenes are mutated versions of protons-oncogenes - they can make this process permanently activated which results in uncontrollable cell division
How do proto-oncogenes stimulate DNA replication?
How do oncogenes lead to uncontrolled cell division?
- can cause the receptor protein on the cell membrane to be permanently activated so cell division is activated even in the absence of growth factors
- code for a growth factor that is produced in excessive amounts so constantly stimulates division
What are tumour suppressor genes and what happens when they become mutated?
- produce proteins which slow cell division and cause cell death if DNA copying errors are detected
- a mutation means that the proteins are not produced, so cell division would continue uncontrollably and mutated cells would not be identified or destroyed
How does methylation affect the tumour suppressor gene?
prevents transcription factors from binding, so tumour suppressor genes cannot be transcribed meaning they are switched off and not expressed, this results in uncontrolled cell division
What is a promoter region?
the sequence on DNA that a transcription factor binds to
How does increased oestrogen increase risk of cancer?
oestrogen acts as a transcription factor so can bind to a gene and initiate transcription, if this is a porto-oncogene then it will be permanently turned on activating cell division
How does methylation affect cancer genes?
- Hypermethylation of tumour suppressor genes prevents them from being active, this stops the production of proteins that would normally inhibit cell division, and cells divide unchecked to form tumours
- Hypomethylation of proto-oncogenes leads to their activation as oncogenes.
This activation promotes excessive cell division and tumour growth, especially as some oncogenes code for growth factors that stimulate further cell division
