Chapter 20 - Gene Expression Flashcards
What is a mutation?
A change in the base sequence of DNA
What are the two types of mutations?
- Gene mutations
- Chromosomal mutations
What are gene mutations?
Any change to quantity of bases or base sequence in DNA
- will result in a change in amino acid sequence of polypeptide (primary structure)
- can arise spontaneously during DNA replication
Within gene mutations, what are the two kinds?
- Point mutations - the mutation affects just one nucleotide/ base e.g. base substitution
= an abnormal protein (different amino acids)
= no protein at all (results in a stop codon)
= a normal protein (genetic code is degenerate so some amino acids are coded for by more than one codon) - Frameshift mutations e.g. base deletion
- removal of one base = frameshift to the left or right etc
What are chromosomal mutations?
Changes in structure or number of whole chromosomes
What are the two types of mutations under chromosomal mutations?
- Polyploidy (in plants) = more than two sets of homologous chromosomes
- Non-disjunction - failure of the chromosomes to separate = abnormal amounts of chromosomes
List 4 other kinds of gene mutations
- Addition of bases (insertion) - an extra nucleotides becomes inserted into the sequence (similar effect as frameshift)
- Duplication of bases - one or more bases are repeated (frameshift to right)
- Inversion of bases - group of bases becomes separated from DNA sequence and rejoin in reverse order
- Translocation of bases - group of bases become separate from DNA sequence on one chromosomes and inserted on another chromosome
What are the causes of mutations?
- arise randomly/ spontaneously during DNA replication (without any outside influence)
- But mutation rate can be increased by outside factors (mutagenic agents/ mutagens)
- high energy ionising radiation (X-rays/ UV light)
- chemicals (benzopyrene - constituent of tobacco smoke)
What are cells like in multicellular organisms?
Cells are differentiated and specialised to carry out a particular function = efficient at each function
(Unlike unicellular organisms)
How does cell differentiation arise?
Gene expression - when a gene is expressed it leads to the production of that protein
- it is irreversible
What are stem cells?
Undifferentiated cells
- retain ability to differentiate into other cell types
- they are relied on to produce cells to maintain and repair tissues + organs
What are the 3 key sources of stem cells?
- Embryonic stem cells
- Foetal stem cells
- Adult stem cells (liver, heart, brain, bone marrow, adipose tissue)
What are the 4 kinds of stem cells?
- Totipotent = can differentiate into any type of cell e.g. embryonic stem cells up to day 4
- Pluripotent = slightly more specialised but can differentiate into almost any cell type (embryos and foetus)
- Multipotent = can differentiate into a limited number of specialised cells e.g. stem cells in bone marrow can become any type of blood cell (red, white etc)
- Unipotent = a cell that has committed and can only differentiate into a single cell type (found in adult tissue)
What is IPS
Induced pluripotent stem cells
- developed from a unipotent cell to treat human disorders
- heart muscle cells = heart damage
- B cells of pancreas = type I diabetes
What is transcription controlled by?
Transcription factors (proteins) - required to ‘switch genes on’ so only specific genes in specific cell types are switched on
- found in cytoplasm of cells
Briefly explain how transcription factors work
- Have a DNA binding site which is complementary to + binds to a specific DNA sequence in the promoter region (before start of every gene)
- These factors activate transcription by recruiting RNA polymerase to bind and carry out transcription of that gene
Explain the control of transcription factors by hormones [5]
- Steroid hormone simply diffuses into the cell + binds to the hormone receptor (lipid soluble)
- Changes the shape of DNA binding site and activates the transcription factor
- It can then move into the nucleus via nuclear pores
- Due to being activated it can now bind to the genes promoter region
- RNA polymerase can now bind and transcribe the gene
What is Epigenetics?
The study of changes in organism genetics caused by modification of gene expression rather than alteration of the genetic code of self
- The environment can cause heritable changes in DNA - by changing the shape of DNA (expression of genes) not DNA sequence itself
Outline the link between chromatin and gene expression
Strong association of DNA + histone proteins
- more condensed (tightly packed)
- heterochromatin
- no access of transcription factors to promoter region
- inactive gene = switched off
Weak association of DNA + histone proteins
- less condensed (loosely packed)
- euchromatin
- access of transcription factors to promoter region
- active gene = switched on
What is the epigenome?
The chemical changes to the DNA + histone proteins (chromatin) of an organism
- They can be passed down to offspring with the DNA
Is the epigenome fixed?
The DNA sequence is fixed (apart from mutations) but epigenome is flexible = the chemical tags respond to environmental changes (diet, stress), adjusting the shape of the DNA-histone complex = switches on/off genes
What are the 2 types of chemical tagging that affects shape of DNA-Histone Complex
- Acetylation of histone proteins
- Methylation of DNA
Explain how acetylation of histone protein works
The addition of an acetyl group to histone proteins (from Acetyl Coenzyme A)
- switches genes on as they are expressed
- the Acetyl group is negatively charged so binds to positive amine group of histone tails + prevents it from binding to negatively charged phosphate groups of DNA
Deacetylation = removal of acetyl group = switches genes off
Explain how methylation of DNA works
a. Attracts proteins that cause deacetylation of histones
b. Blocks promoter regions - prevents transcription factors binding
- both result in switching genes off
What is another way of controlling gene expression?
Controlling translation
Explain how controlling translation to control gene expression works
- Double-stranded RNA is broken up by an enzyme into small interfering RNA (siRNA)
- One of the two strands of siRNA combines with an enzyme
- The siRNA strand pairs with complementary bases on a mRNA strands
- The enzyme cuts the mRNA into smaller sections
How are epigenetics and disease linked?
Epigenetics changes are normal but can also cause certain diseases
- Changing of normal epigenome can cause abnormal silencing/inactivation or activation of genes
E.g. cancer
What is cancer?
A group of diseases caused by mutations to genes that regulate the cell cycle and mitosis thus resulting in uncontrolled growth in cells
What are the two types of tumour?
- Benign = non-cancerous tumour
- Malignant = cancerous tumour
Briefly outline benign tumours
- can grow to a large size but very slowly
- cells produce adhesion molecules on the surface membranes causing them to stick together so remain within tissue they are found in and don’t spread
- Surrounded by dense capsule so remain as compact structure
- Less likely to be life-threatening but can disrupt functioning of nearby organs
- localised effects
- Removed by surgery + rarely recurs after removal
Briefly outline malignant tumours
- can go to a large size but very rapidly
- Large nucleus and appear darker due to large amounts of DNA
- cells often unspecialised, unlike benign
- No adhesion molecules so tend to spread to other areas of body (metastasis)
- tumours not surrounded by capsule = grow finger like projections into surrounding tissues
- Life-threatening and has affects on whole body
- Removal via chemotherapy, radiotherapy and surgery
What is metastasis?
The process by which primary tumours spread into secondary tumours in other areas
What are the two main genes involved in cell division = development of cancer?
- Proto-oncogenes = accelerator for cell division
- Tumour suppressor genes = break for cell division
E.g. TP53, BRCA1 and BRCA2
Explain how proto-oncogenes work
- When expressed it starts cell division
- Can mutate into oncogene due to too much acetylation = tumour
- only takes a single mutated allele for oncogene to be activated
Explain how tumour suppressor genes work
- Activated to stop tumour formation
- Increase inactivation due to methylation can lead to tumour formation as cell division doesn’t stop
- Takes a mutation to both alleles to inactivate tumour suppressor genes
What is the difference between hypermethylation and hypomethylation?
- Hypermethylation of tumour suppressor genes is a common cause of tumour development
- Hypomethylation (reduced methylation) of proto-oncogenes can lead to more formation due to activation of oncogenes
What are genome projects?
Projects that determine the entire DNA base sequence of different organisms (including humans) producing a complete map of the entire genome (exact gene loci on each chromosome) for the organism
How is DNA sequenced using whole genome shotgun (WGS) sequencing?
- DNA is cut into small, easily sequenced sections
- Using a computer, overlapping segments are aligned until the whole genome is assembled
What are SNP’s?
Single nucleotide polymorphisms
- sequencing of peoples DNA and comparing to human genome has allowed quick identification of SNP’s that result in diseases/ disorders
- so earlier treatment can occur
What do the terms proteome, cellular proteome and complete proteome mean?
Proteome = all proteins produced by the genome
Cellular proteome = in a given cell type
Complete proteome = in whole organism
How is the genome sequenced for simpler organisms?
Human microbiome project - the genomes of thousands of prokaryotic and single-celled eukaryotic organisms are currently being sequenced
● The information gained could help to cure many diseases
● Determining the genome for prokaryotic organisms is easier as they only have one circular piece of DNA and have no non-coding DNA (introns)
