t8 gene expression Flashcards
definition of gene mutation
change in the DNA base sequence
definition of epigenome
all of the chemical modifications to histone proteins and DNA in an organism
definition of epigenetics
inheritable changes in gene function, without changes to DNA base sequence
what is a transcription factor
protein that initiates the transcription of genes by binding to specific base sequences on DNA (promoter region) and allowing RNA polymerase to bind
what is a mutagenic agent + examples
factor that increases the rate of mutations
eg. UV light, X-rays, asbestos, alpha and beta particles
6 types of mutation (brief)
- addition
- deletion
- substitution
- duplication
- translocation
- inversion
what is an addition mutation
-an extra nucleotide (with a new base) is inserted into the DNA base sequence, causing a frame shift to the RIGHT
-can dramatically change the amino acid sequence produced, affecting the tertiary structure of the polypeptide, potentially leading to a non-functional protein
-however, if 3 bases are inserted, frame shift wont occur
what is a deletion mutation
-nucleotide (and its base) is randomly deleted from the DNA base sequence, causing a frame shift to the LEFT
-can dramatically change the amino acid sequence, affecting the tertiary structure, potentially leading to a non-functional protein
what is a substitution mutation
-a base in the DNA sequence is randomly swapped for a different base
-only affects the amino acid for the triplet in which the mutation occurs (no frame shift)
-can cause silent mutation (no change to amino acid sequence as genetic code is degenerate), missense mutation (alters single amino acid) or nonsense mutation (causes premature stop codon)
what is a duplication mutation
-a whole gene or section of a gene is repeated, so 2 copies of the same gene/section appear on the same chromosome
-produces frame shift to the RIGHT
what is an inversion mutation
-a group of bases become separated from the DNA sequence and then rejoin in the same position, but in the reverse order
-affects multiple amino acids, affecting the tertiary structure, so potentially leading to a non-functional protein
-usually occur during crossing-over in meiosis
what is a translocation mutation
-a group of bases becomes separated from the DNA and rejoins on a separate gene or to the same chromosome in a different location
-the cut gene is now non-functional as it has a section missing, and the gene that has gained the translocated section is likely to be non-functional.
benefit of mutation
-produce the genetic diversity necessary for natural selection and speciation
costs of mutations
-almost always harmful and produce an organism less suited to its environment
-mutations in body cells lead to disruptions of regular cellular activity eg. mutations in cell division processes can lead to cancer
-cause hereditary mutations when they occur in gametes
what is a stem cell
-unspecialised cells that can divide by mitosis an unlimited number of times
-can make copies of themselves, or develop into specialised cells by differentiation
what is cell differentiation
-process by which a cell develops into a specialised cell suited for its role by producing different proteins
what are totipotent stem cells
-can divide and produce any type of body cell INCLUDING new embryonic cells and placental cells
-initially unspecialised, but specialise during embryonic development
-exist for a limited time in early embryos
what are pluripotent stem cells
-can divide and produce any type of body cell EXCEPT placental cells
-can divide an unlimited number of times and keep replacing themselves, allowing them to be used in treating human cells (iPS cells)
what are multipotent adult stem cells
-can differentiate into a limited range of cell types, and are used to produce new cells for the processes of growth, cell replacement and tissue repair
-found in the bone marrow - these can only differentiate into blood cells (rbcs, phagocytes and lymphocytes)
what are unipotent stem cells
-adult cells that can only differentiate into a single type of cell in their own lineage
-eg. cardiomyocytes - unipotent type of stem cell found in the cardiac muscle that is important after damage through heart attack or age
what are induced pluripotent stem cells (iPS cell)
-produced from adult somatic (body) cells using transcription factors
-transcription factors cause specific genes to be expressed which revert cell back to its pluripotent state
-could be used to generate transplants without the risk of immune rejection
2 types of transcription factors + explanation
- activators - stimulate/increase rate of transcription by helping RNA polymerase bind to the promoter region
- repressors - inhibit/decrease the rate of transcription by binding to the promoter region and blocking RNA polymerase from binding
how does oestrogen affect transcription
- diffuses through phospholipid CS membrane (as it is lipid-based due to being a steroid hormone)
- binds to transcription factor in the cytoplasm, forming oestrogen-oestrogen receptor complex, changing the shape of the transcription factor and making it complementary to the DNA
- complex enters the nucleus through nuclear pore and binds to promoter region on DNA
- RNA polymerase can then attach to the DNA, initiating transcription
how are changes to the epigenome made
-changed in environment eg. toxins from smoking, stress, exercise and diet
2 types of epigenetic tags (brief)
- increased methylation of DNA
- decreased acetylation of histones
effect of increased methylation of DNA
-addition of methyl groups to DNA causes DNA to coil tightly, preventing transcription factors from binding, preventing transcription
effect of decreased acetylation of histones
when acetyl groups are removed from histones, the DNA coils tightly, preventing transcription factors from binding, preventing transcription
cancer treatments - what do drugs that reverse epigenetic changes do
- removal of methyl groups from DNA of tumour suppressor genes will enable them to be expressed, regulating the cell cycle and stopping tumour development
- removal of acetyl groups from histones attached to oncogenes causes the DNA to wrap more tightly, silencing these genes (turns them back into proto-oncogenes). this causes cell death (apoptosis)
how does small interfering RNA (siRNA) regulate transcription
- an enzyme cuts large, double stranded molecules of RNA into smaller sections called siRNA
- one of the 2 strands combines with another enzyme, and the siRNA molecule guides the enzyme to an mRNA molecule via complementary base pairing
- once in position, the enzyme cuts the mRNA into smaller sections, so the mRNA is no longer capable of being translated into a polypeptide. this means the gene has not been expressed
properties of benign tumours
-grow very slowly
-are contained and dont metastasise
-often specialised
-can usually be removed through surgery alone
-rarely reoccur after treatment
properties of malignant tumours
-grow rapidly
-are uncontained and can metastasise
-often unspecialised
-removal involves surgery and chemo/radiotherapy
-can reoccur after treatment
how can oestrogen cause breast cancer
-increased oestrogen concentrations in fatty tissue of the breast in post-menopausal women can be linked to breast cancer as oestrogen binds to transcription factors, activating the genes promoting cell division, leading to tumour formation.
risk factors for cancer
- genetic risks
- environmental risks - alcohol, radiation exposure, smoking, lack of exercise and high-fat diet linked to obesity
3 methods of producing DNA fragments (brief)
- using reverse transcription
- using restriction endonucleases to extract genes
- gene machine
process of reverse transcription for producing DNA fragments
-a cell that naturally produces the protein of interest is selected (as they should contain large amounts of mRNA for the protein)
-the reverse transcriptase enzyme join the DNA nucleotides w complementary bases to the mRNA sequence (which acts as a template), and a single stranded DNA is made (cDNA) using DNA polymerase
process of using restriction endonucleases to produce DNA fragments
-cut DNA at specific base sequences (recognition sites)
-can produce ‘blunt ends’ by cutting at the same location in the double strand or ‘sticky ends’ where they cut at palindromic sequences to create staggered ends
process of gene machine for producing DNA fragments
-examine protein of interest to identify amino acid sequence and then work out the mRNA and DNA sequences of the protein
-DNA sequence is then entered into a computer to create small sections of overlapping single strands of nucleotides that make up the gene, which can be joined to create the DNA for the entire gene.
why is it easier to identify genome of simple prokaryotic organisms + benefit of this
-dont contain introns, so their genome can be used directly to sequence the proteins that derive from the genetic code of the organism
-useful for identifying potential antigens to use in a vaccine
how does a genome project work
-collecting DNA samples from many individuals of a species and sequencing (identifying base sequence) and comparing them to create a reference genome.
