Gene expression Flashcards
Mutation
change in the quantity or structure of DNA in an organism
Gene mutation
change or rearrangement of nucleotide bases in DNA
Explain why a change in the amino acid sequence of a polypeptide can result in an inactive protein(3)
-Different amino acid results in different tertiary structure
-This means that the shape of the protein changes due to the different bonds forming
-This change in shape will affect the functionality of the protein, especially if an enzyme (active site no longer complementary to substrate)
Explain why not all gene mutations result in inactive proteins(3)
-The change in base may result in the same amino acid being produced
-Due to the degenerate code
-Tertiary structure of the protein will not change
Explain the effect of a frame shift caused by a gene mutation. Discuss the positioning on the base sequence of the mutation (4)
-Reading frame for the codons has been shifted by one base.
-The wrong 3 bases are now read as a triplet
-Codes for a different amino acid from that point forward
-Tertiary structure of protein different and protein likely to be dysfunctional
-Mutation near the start of the base sequence results in a more drastically altered protein
Describe the causes of mutations
-Arise spontaneously during DNA replication
-High energy ionising radiation
-Chemicals
Substitution
Substitution: one nucleotide is replaced by another with different base
Consequences of substitution
-formation of one the three stop codons that marks of the end of a polypeptide. The production of the polypeptide coded for is stopped prematurely and the protein would be different and not function normally
-The formation of a codon for a different amino acid meaning that the structure of the polypeptide would be different
-The formation of a different codon but one that produces a codon for the same amino acid as before
Discuss the causes of gene mutations
-Natural mutation rate (spontaneous mutation) is 1 mutation per 100 000 genes per generation. Mutagenic agents increase this rate:
-High energy ionising radiation: eg alpha and beta radiation, x rays, UV light.
-Chemicals: eg nitrogen dioxide alters DNA structure of interferes with transcription
Deletion
loss of a nucleotide base from the DNA sequence, causes a frameshift
Consequences of deletion
causes a frameshift. All bases following the substitution shifted to the left causing remaining to codons to be different and potentially code for different amino acids
Addition
addition of a nucleotide base in a sequence, causes a frameshift
Consequences of addition
causes a frameshift. All bases following the substitution shifted to the right causing remaining to codons to be different and potentially code for different amino acids
Duplication
one or more bases repeated, causes a frame shift
Consequences of duplication
causes a frameshift. All bases following the substitution shifted to the right causing remaining to codons to be different and potentially code for different amino acids
Inversion
sequence of bases separated from the DNA sequence and then reattach in the same place but the opposite order
Consequences of inversion
amino acid sequence in the area of inversion affected
Translocation
group of bases separated from the DNA sequence on one chromosome and inserted into the DNA sequence on a different chromosome
cell differentiation
process by which cells develop into specicalised cells. No one cell can provide the best conditions for all functions. More efficient if they are adapted to their function
what is a stem cell
the only cell that can differentiate and divide into identical copies through a process of self renewal
State what totipotent cells are
Totipotent cells can develop into any types of cell, eg fertilised egg
What happens to totipotent stem cells during embryonic development
Certain parts of the DNA are selectively translated so that only some genes are switched on in order to differentiate the cell into a specific type and form the tissues that make up the foetus
Explain how cells lose their totipotency and become specialised
During specialisation only some genes are expressed so the cell only makes the proteins it needs to carry out its specialised function. A variety of stimuli ensure that the genes that are not needed stay switched off.
What are the ways in which genes are prevented from expressing themselves
-preventing transcription and so preventing the production of mRNA
-prevening translation
4 sources of stem cells in mammals
-embryonic stem cells- from early stage of embryo development and can become any type of cell
-umbilical cord stem cells- similar to adult stem cells
-placental stem cells-develop into specific stem cells
-adult stem cells- found in body tissues of all ages specific to particular tissue
Once specialised can cells develop into other types of cells
most specialised cells can no longer develop into any other cell
What are the 4 types of stem cells
-totipotent
-pluripotent
-multipotent
-unipotent
Totipotent stem cells
Totipotent: in early embryo – develop into any type of cell. Zygote is totipotent. It develops into … (pluripotent stem cells)
pluripotent stem cells
in embryos – become almost any type of cell. Eg embryonic and foetal stem cells
Multipotent stem cells
in adults – differentiate into a limited number of specialised cells. Eg bone marrow make blood cells. Examples of multipotent – adult stem cells, umbilical cord stem cells.
Unipotent stem cells
differentiate into single type of cell – derived from multipotent cells and found in adult tissue
Explain how pluripotent stem cells can be used to treat human disorders
Cells can be used to regrow tissues that have been damaged:
Skin grafts for burns.
Heart muscle cells for heart damage
Nerve cells for MS, spinal injury etc
Blood cells for leukaemia
Bone cells for osteoporosis
Retina cells for macular degeneration
Induced pluripotent stem cells (iPS)
They are a type of pluripotent cell that is produced from unipotent stem cells. The unipotent cell may be almost any body cell
Importance of iPS
Body cell altered in lab to give characteristics of embryonic stem cell. Causes gene and transcriptional factors in the cell to be expressed that are normally switched off
What makes iPS ideal
Can self-renew so limitless supply ideal for medical research and treatment and avoid ethical issues from use of embryonic stem cells
transcription factor
A protein that controls the transcription of genes so that only certain parts of the DNA are expressed
Activators
transcription factors that increase the rate of transcription – e.g. they help RNA polymerase bind to the start of the target gene and activate transcription.
Repressors
decrease the rate of transcription e.g. they bind to the start of the target gene, preventing RNA polymerase from binding, stopping transcription.
Describe the action of activator transcription factors
-activator transcription factors enter the nucleus from the cytoplasm through nuclear pores
-Binds to the promoter region of the specific gene
-The binding of the activator transcription factors allows RNA polymerase to bind to the promoter region
-This allows the gene to be transcribed
Describe the action of repressor transcription factors
-Repressor transcription factors enter the nucleus from the cytoplasm through nuclear pores.
-binds to promoter region of a specific gene
-The binding of a repressor transcription factor blocks the binding of RNA polymerase
-Prevents gene from being transcribed
How does Oestrogen effect gene expression
-Oestrogen is lipid soluble and diffuses through the phospholipid bilayer
-binds to the transcription factor
-transcription factor is a protein and binding of oestrogen causes the tertiary structure to change
-transcription factor no longer acts as expected (activator or repressor)
siRNA
siRNA molecules are short, double-stranded RNA molecules that can interfere with the expression of
specific genes.
Their bases are complementary to specific sections of a target gene and the mRNA that’s formed from
it.
RNA interference
-Double-stranded siRNA is unwound into two single-stranded siRNA molecules by an enzyme.
-In the cytoplasm, single-stranded siRNA and associated proteins bind to the target mRNA.
-The proteins cut up the mRNA into small sections – can no longer be translated and the production of the specific protein in inhibited.
State what is meant by epigenetics
Heritable changes in gene function due to environmental factors that do not change the base sequence of DNA
Describe the nature of the epigenome
The epigenome is a series of chemical tags attached to DNA and histones that affects the transcription of DNA
What does the epigenome determine
the shape of the DNA histone complex. E.g. it keeps genes that are inactive in a tightly packed arrangement and therefore ensures that they cannot be read (switched off)
The epigenome is flexible, because its chemical tags respond to environmental changes – how?
An environmental factor stimulates proteins to carry its message inside the cell from where it is passed by a series of proteins into the nucleus.
Inside the nucleus, the message passes to a specific protein which can be attached to a specific sequence of bases on the DNA.
Once attached the protein has two possible effects.
-It can change the acetylation of histones leading to the activation or inhibition of a gene.
-It can change the methylation of DNA by attracting enzymes that can either add or remove methyl groups.
epigenetic silencing
To switch off (inactivate) genes
Explain the effect of epigenetic factors on DNA and histones
The epigenome determines the shape of the DNA-histone complex by changing how tightly wrapped the DNA is. When tightly wrapped the DNA cannot be transcribed, when loosely coiled DNA can be transcribed
Explain the effects of decreased acetylation of histones
-Gene switched off (inactive):
-Decreased acetylation of histones
-Increased positive charges on histones which increases attraction to phosphate groups on DNA
-Genes tightly packed (condensed)
-Transcriptional factors cannot bind
-Transcription cannot occur so mRNA is not made
-Protein is not produced
Explain the effects of increased methylation of DNA
-Gene switched off (inactive):
-Increased methylation of DNA
-Prevent binding of transcriptional factors to DNA
-Attract proteins that condense DNA/histone complex by inducing deacetylation
-Genes tightly packed (condensed)
-Transcriptional factors cannot bind
-Transcription cannot occur so –mRNA is not made
-Protein is not produced
Epigenetics in rats
Good maternal behaviour in rats transmits epigenetic information onto their offspring’s DNA without changing the sequence of bases in their DNA.
Epigenetics in humans
In humans, when a mother has gestational diabetes, the fetus is exposed to high concentrations of glucose.
These high concentrations of glucose cause epigenetic changes in the daughters DNA, increasing the likelihood that she will also develop gestational diabetes.
methylation and cancer
There are specific sections of DNA (near promoter regions) that have no methylation in normal cells.
In cancer cells these regions have become highly methylated causing genes that should be active to be silenced.
This abnormality happens early in the development of cancer.
Epigenetic therapy
Involves using drugs that’s inhibit enzymes either involved in histone acetylation or DNA methylation.
Drugs that inhibit enzymes that cause DNA methylation can reactive genes that have been silenced – e.g. genes that repair damaged cells
Epigenetic therapy must only target cancer cells – why?
If the drugs targeted normal cells they could activate gene transcription and make them cancerous.
cancer
group of diseases caused by damage to the genes that regulate mitosis
