Cellular control Flashcards
What is a mutation?
A sudden (heritable or non-heritable) change in DNA (bases or nucleotides).
What are mutagens?
The agents which cause mutations.
What are the types of mutagens?
Physical, chemical and biological.
What is an example of a physical mutagen?
UV rays, gamma radiation, X rays
What is an example of a chemical mutagen?
Benzopyrene (found in tobacco smoke), mustard gas, nitrous acid, aromatic amines, free radicals, colchicine
What is an example of a biological mutagen?
Transposons, some viruses, food contaminants such as mycotoxins from fungi
What are the types of gene mutations?
- Point / Substitution
- Indel (Deletion or Insertion)
What happens in a point / substitution mutation?
One base pair replaces another.
What happens in a deletion mutation?
One or more nucleotides are deleted from a length of DNA.
What happens in an insertion mutation?
One or more nucleotides are added to a length of DNA.
What does the sequence of bases in DNA code for?
The sequence of amino acids in a protein.
What is a neutral mutation?
A type of mutation where the protein produced by it does not harm the organism or benefit it.
What are the 2 types of indel mutations?
Insertions and deletions
What do indel mutations cause?
A frameshift
What is a frameshift mutation?
When nucleotide base pairs, NOT IN MULTIPLES OF THREE, are inserted into or deleted from the gene. Because the genetic code is non-overlapping and read in groups of the bases, all the subsequent base triplets are altered.
What are the types of point / substitution mutations?
- Silent
- Missense
- Nonsense
What is a silent mutation and why do these occur?
A point mutation which involves a change to the base triplet, where that base triplet still codes for the same amino acid. This can happen due to the degenerate nature of the genetic code, where the majority of amino acids (apart from methionine) have more than one base triplet code.
How do silent mutations alter proteins?
They do not - the primary structure is not altered.
What is a missense mutation?
A point mutation which involves a change to the base triplet sequence, which leads to a change in the amino acid sequence in a protein. The change to the primary structure leads to a change to the tertiary structure of the protein, altering its shape and preventing it from carrying out its normal function.
What disease is caused by a missense mutation?
Sickle cell anaemia
What is a nonsense mutation?
A point mutation which alters a base triplet so that it becomes a termination (stop) triplet. This results in a truncated protein that will not function. This abnormal protein will most likely be degraded within the cell.
What disease is caused by a nonsense mutation?
Duchenne muscular dystrophy
How can a frameshift affect protein function?
When the mRNA from the mutated gene is translated, after the frameshift, the amino acid sequence is severely disrupted. The primary structure and therefore tertiary structure is much altered and so the protein cannot carry out its normal function. If this protein is very abnormal it will be rapidly degraded within the cell.
What disorder results from frameshifts due to deletions of nucleotide bases?
a-thalassaemia
What would the insertion / deletion of a triplet of base pairs result in?
Either the addition or loss of an amino acid - does not result in a frameshift.
Which disease results from an expanding triple nucleotide repeat?
Huntington disease - if the number of repeating CAG sequences goes above a certain critical number, then the person with that genotype will develop symptoms of Huntington disease in later life.
What are examples of beneficial mutations?
- Blue eyes - Enabled people to see better in less bright light in temperate zones.
- Melanin - In Africa the high concentrations of melanin protected people from sunburn and skin cancer. But in temperate regions paler skin enabled vitamin D to be made with a lower intensity of sunlight - protected people from rickets, heart disease and cancer.
What are examples of neutral mutations?
- Inability to smell certain flowers, including freesias and honeysuckle.
- Differently shaped ear lobes.
What does the bacterium E. coli normally metabolise as a respiratory substrate?
Glucose
What happens to E. coli if glucose is not present to be metabolised for respiration?
If lactose is present then this induces the production of lactose permease and B-galactosidase.
What does lactose permease do?
It allows lactose to enter the bacterial cell.
What does B-galactosidase do?
Hydrolyses lactose into glucose and galactose.
What type of carbohydrate is lactose?
A disaccharide
Which 2 regions are the control sites?
The operator region and the promoter region
How many base pairs long is the lac operon?
6000
What is the operator region also called?
lacO
What is the promoter region also called?
P
What are the structural genes on the lac operon?
lacZ and lacY
What do the structural genes on the lac operon code for?
lacZ codes for B-galactosidase
lacY codes for lactose permease
What binds to the promoter region?
RNA polymerase
What gene exists a small distance away from the operon?
Regulatory gene I
What does the regulatory gene I code for?
A repressor protein, LacI
What happens when the regulatory gene I is expressed?
LacI binds to the operator, preventing RNA polymerase from binding to the promoter region. Therefore it prevents the genes lacZ and lacY from being transcribed (expressed) so the enzymes for lactose metabolism are not made. The genes are ‘off.’
What happens to the LacI repressor proteins when glucose is absent and lactose present?
Molecules of lactose bind to the LacI repressor protein molecules. This alters the shape of the LacI repressor protein, preventing it from binding to the operator. RNA polymerase can then bind to the promoter region and begin transcribing the structural genes into mRNA that will then be translated into the two enzymes.
What is the role of lactose in the lac operon when glucose is absent?
It induces the enzymes needed to break itself down.
What are transcription factors?
Proteins or short non-coding pieces of RNA that act within the cell’s nucleus to control which genes in a cell are turned on or off.
How do transcription factors carry out their function?
They slide along a part of a DNA molecule, seeking and binding to their specific promoter regions. They may then aid or inhibit the attachment of RNA polymerase to the DNA, and activate or suppress transcription of the gene.
What is the role of transcription factors in eukaryotes?
Regulation of gene expression, making sure that different genes in different types of cells are activated or suppressed.
What process are some transcription factors involved in regulating?
The cell cycle
What are 2 types of genes which help regulate cell division via transcription factors?
Tumour suppressor genes and proto-oncogenes. Mutations to these genes can lead to uncontrolled cell division or cancer.
What is unique about the location of the promoter region on DNA?
Many genes have their promoter regions some distance away, along the unwound length of DNA but, because of how DNA can bend, the promoter region may not be too far away spatially.
What are the non-coding regions of DNA within a gene?
Introns
What are the coding / expressed regions of DNA within a gene?
Exons
Are introns or exons transcribed?
Both
What is the result of transcription of introns and exons referred to as?
Primary mRNA
What happens to primary mRNA after having been transcribed?
It is edited and the RNA introns, which correspond to the DNA introns, are removed. The remaining mRNA exons are joined together.
Which enzyme is involved in he editing and splicing process of primary mRNA?
Endonuclease
What can some introns themselves encode?
Proteins
What do some introns become?
Short non-coding lengths of RNA involved in gene regulation.
How can a length of DNA encode more than one protein?
Sometimes more than one protein can be encode for by one length of DNA depending on how it is spliced.
How are many enzymes activated?
By being phosphorylated.
What happens in the first step of enzyme activation?
A signalling molecule, such as the protein hormones glucagon, binds to a receptor on the plasma membrane of the target cell.
What is activated after the signalling molecule binds to the cell’s plasma membrane?
A transmembrane protein which then activates a G protein.
What does the activated G protein do?
It activates adenyl cyclase enzymes.
What do the activated adenyl cyclase enzymes do?
They catalyse the formation of many molecules of cAMP from ATP.
What does cAMP activate?
PKA (protein kinase A)
What does activated PKA catalyse?
The phosphorylation of various proteins, hydrolysing ATP in the process. This phosphorylation activates many enzymes in the cytoplasm e.g. those that convert glycogen to glucose.
What does PKA phosphorylate?
A CREB protein
What happens to the CREB protein?
It enters the nucleus and acts as a transcription factor, to regulate transcription.
What are homeotic genes invovled in?
They are involved in controlling the anatomical development, or morphogenesis, of an organism, so that all structures develop in the correct location, according to the body plan.
What do several homeotic genes contain?
Homeobox sequences, sometimes called homeobox genes.
What are homeobox sequences?
Sequences of 180 base pairs (excluding introns) found within homeotic genes which are involved in regulating patterns of anatomical development in animals, fungi and plants.
What does each homeobox sequence encode for?
A 60-amino acid sequence, called a homeodomain sequence, within a protein.
What do homeodomain sequences do?
They can old into a particular shape and bind to DNA, regulating the transcription of adjacent genes.
What do homeodomain-containing proteins act as?
Transcription factors which act within the nucleus.
What is the shape of homeodomain-containing proteins?
Folds into a shape called H-T-H. It consists of two alpha helices (H) connected by one turn (T).
What does part of the homeodomain sequence recognise?
The TAAT sequence of the enhancer region (a region that initiates or enhances transcription) of a gene to be transcribed.
What is interesting about homeobox gene sequences?
They have been highly conserved since before the Palaeozoic era (541 million years ago). The sequences are also similar in all organisms.
What are Hox genes?
A subset of homeobox genes, found only in animals. They are involved in the formation of anatomical features in the correct locations of the body plan.
