6.1- Cellular control Flashcards
What are genetic mutations
- Mutation is a random change to the genetic material
- Some involve changes to structure or number of chromosomes
- Gene mutation is change to DNA
What can cause genetic mutations
- May occur spontaneously during DNA replication before cell division
- Certain chemicals e.g. Tar in tobacco smoke, and ionising radiation e.g. UV light, X-rays and Gamma rays, may be mutagenic
When do mutations occur
- Structure of DNA makes it stable and fairly resistant to corruption of genetic information stores within it
- Errors may occur, however, during DNA replication (where they are most likely top occur in cell cycle
Describe the passing on of mutations to offspring
- Mutations associated with mitotic division are somatic mutations- not passed int offspring. May be associated with development of cancerous tumours
- Mutations associated with meiosis and gamete formation may be inherited by offspring
Name 2 categories of genetic mutation
- point
- indel
Outline point mutations
The genetic code consists of nucleotide base triplets within the DNA. During transcription of a gene, this code is copied to a length of mRNA as codons, complementary to the base triplets on the template strand of the length of DNA .The sequence of codons on the mRNA is therefore a copy of the sequence of base triplets on the gene (coding strand of the DNA).
Point mutations are a base substitution.
name 3 types of point mutation
Silent, Missense, Nonsense
Describe silent mutations
- All amino acids involved in proteins synthesis apart from methionine) have more than one base triplet code
- This reduces the effect of point mutations, as they do not always cause a change to the sequence of amino acids in a protein
- Often called the ‘redundancy’ or ‘degeneracy’ of the genetic code
- Involves change to base triplet where that triplet still codes for the same amino acid
- Primary structure of the protein, and therefore the secondary and tertiary structure, is not altered
Describe missense mutations
- Change to base triplet sequence that leads to change in amino acid sequence in a protein
- Within a gene, point mutation may have significant effect on protein produced- alteration to primary structure leads to change to tertiary structure of the protein- altering its shape and preventing it from carrying out its function
- May not make large difference if in non-essential part of protein or substitutes amino acid with similar properties
- Example- Sickle cell anemia results from missense mutation on the sixth base triplet of the gene for the beta-polypeptide chains of haemoglobin: the amino acid valine, instead of glutamic acid, is inserted at this position- This results in deoxygenated haemoglobin crystallising within erythrocytes, causing them to become sickle shaped, blocking capillaries and depriving tissues of oxygen
Describe missense mutations
- Change to base triplet sequence that leads to change in amino acid sequence in a protein
- Within a gene, point mutation may have significant effect on protein produced- alteration to primary structure leads to change to tertiary structure of the protein- altering its shape and preventing it from carrying out its function
- May not make large difference if in non-essential part of protein or substitutes amino acid with similar properties
- Example- Sickle cell anemia results from missense mutation on the sixth base triplet of the gene for the beta-polypeptide chains of haemoglobin: the amino acid valine, instead of glutamic acid, is inserted at this position- This results in deoxygenated haemoglobin crystallising within erythrocytes, causing them to become sickle shaped, blocking capillaries and depriving tissues of oxygen
Describe nonsense mutations
- Point mutation may alter a base triplet so it becomes a termination (stop) triplet
- Particularly disruptive point mutation
- Results in truncated protein that won’t function
- This abnormal protein will most likely be degraded within the cell
- Example- genetic disease Duchenne muscular dystrophy
Outline indel mutations
Cause a frameshift in sequence of amino acids
Name 2 types of indel mutations
Insertions (incl. expanding triple nucleotide repeats), Deletions
Describe insertions and deletions
- If nucleotide base pairs, not in multiples of 3, are inserted in the gene or deleted from the gene, because the code is non-overlapping and read in groups of three bases, all the subsequent base triplets are altered
- This is a frameshift
- When the mRNA from such a mutated gene is translated, the amino acid sequence after the frameshift is severely disrupted- the primary sequence of the protein, and subsequently the tertiary structure, is much altered- consequently, the protein cannot carry out its normal function
- if the protein is very abnormal, it will be rapidly degraded within the cell
- Insertions or deletions of a triplet of base pairs will result in the addition or loss of an amino acid, not in a frameshift
- Example- some forms of thalassaemia, a haemoglobin disorder, result from frameshifts due to deletions of nucleotide bases
Describe expanding triple nucleotide repeats
- Some genes contain a repeating triplet such as -CAG CAG CAG-
- In an expanding triple nucleotide repeat, the number of CAG triplets increases at meiosis and again from generation to generation.
- Example- Huntington disease results from an expanding triple nucleotide repeat- If the number of repeating CAG sequences goes above a certain critical number, then the person with that genotype will develop the symptoms of Huntington disease later in life
Describe he harmfulness of genetic mutations
- Many mutations are beneficial- help drive evolution through natural selection e.g. mutation for blue eyes may enable people to see better in less bright light in temperate zones - Different alleles of a particular gene are produced via mutation
- Some mutations can appear to be neutral- neither beneficial nor harmful- such as those in humans that cause inability to smell certain flowers (incl. freesias and honeysuckle), and differently shaped earlobes
Describe the lac operon (prokaryotic cells)
- contains P and lacO (control sites, and lacZ and lacY (structural genes)
Describe control sites on the lac operon
- P- promoter region- RNA polymerase binds here which beings transcription of structural genes lacZ and lacY
- lacO- operator region- binds to repressor protein
Describe what occurs when e.coli is grown on glucose, and why this is advantageous
1) I (regulatory gene) codes for repressor protein
2) Repressor protein binds to lacO
3) Means RNA polymerase can’t bring to promotor region
4) Prevents transcription and thus translation- lacZ and lacY can’t be expressed-genes are off- β-Galactosidase and lactose permease not made
This is advantageous because E.coli can directly respire glucose- would be waste of amino acids and energy to produce enzymes for respiring lactose
Describe regulation of gene expression and the transcriptional level in eukaryotic cells
- For a gene to be transcribed, the enzyme RNA polymerase (needed to produce the mRNA) must attach to the control site for that gene- attaches to the promoter.
- In eukaryotes, RNA polymerase can only attach to the promoter with the help of a transcription factor
- Transcription factors slide along a part of the DNA molecule, seeking and binding to their specific promotor regions
- Once it’s bound to the promoter it makes it either easier or harder for RNA polymerase to then also bind to the promoter of the gene
- The transcription factor (or factors as there can be more than 1) therefore either activates or supresses transcription of the structural gene
Describe Post-transcriptional gene regulation
- All the DNA of a gene (including introns and exons) are transcribed
- This results in primary mRNA
- Primary RNA s edited and the RNA introns (lengths corresponding to the DNA introns) are removed
- The remaining mRNA exons (corresponding to the DNA exons) are joined together
- Endonuclease enzyme may be involved in the editing and splicing process
- Some genes can be spliced in different wats- a length of DNA with its introns and exons can, according to how it is spliced, encode more than one protein
Process of post-translational gene regulation
1) A signalling molecule, such as the protein hormone glucagon, binds to a receptor on the plasma membrane of the target cell.
2) This activates a transmembrane protein which then activates a G protein.
3) The activated G protein activates adenyl cyclase enzymes.
4) Activated adenyl cyclase enzymes catalyse the formation of many molecules of cAMP from ATP.
5) CAMP activates PKA (protein kinase A).
6) Activated PKA catalyses the phosphorylation of various proteins, hydrolysing ATP in the process. This phosphorylation activates many enzymes in the cytoplasm, for example those that convert glycogen to glucose.
7) PKA may phosphorylate another protein (CREB, CAMP response element binding).
8) This then enters the nucleus and acts as a transcription factor, to regulate transcription.
Describe the sequence of events during apoptosis
1) enzymes break down the cytoskeleton
2) The cytoplasm becomes dense with tightly packed organelles
3) the cell surface membrane changes and small protrusions called blebs form
4) Chromatin condenses, the nuclear envelope breaks and DNA breaks into fragments
5) the cell breaks into vesicles tat are ingested by phagocytic cells, so that cell debris doesn’t damage any other cells pr tissues
- the whole process happens quickly
