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Cellular Control

- There are some mutagenic chemicals which can make a mutation more likely but mutations are random so nothing will make one guaranteed

- These include tar in tobacco smoke, ionising radiation (UV light etc.)

  • -  2 Key types of mutation:

    • -  Point mutation: a base pair may be replaced and substituted

    • -  Insertion or deletion (indel mutations - means insertion/deletion): this may cause

      a frameshift as one or more nucleotides are inserted or deleted

  • -  Point Mutation: There are 3 types of point mutation, these are all surrounding a base

    being substituted or replaced

    • -  Silent Mutation: The genetic code is degenerate and as a result multiple triplets

      will code for the same amino acid in many cases. This is key in playing a role in decreasing the effect of a mutation as they do not always cause a change to the sequence of amino acids in a protein. If a mutation is caused and the there is no change to the primary structure of the protein this mutation is silent

    • -  Missense Mutation: If there is a change in the sequence that leads to an altered amino acid sequence in the protein this is a missense mutation. Such a change may cause alterations of the secondary and tertiary structure causing it to be ineffective as a protein or stop it from carrying out its function (example is sickle cell anaemia)

    • -  Nonsense mutation: This is when a mutation alters the base sequence such that a stop codon is formed/ stop triplet. This will result in a short protein that is unlikely to function (example is duchenne muscular dystrophy)

    • -  Fundamentally: silent - no change, missense - change to another amino acid, nonsense - change to a stop codon

  • -  Indel/Insertion and Deletion Mutations: If a base pair is inserted into a gene or deleted it will cause a frameshift as DNA is non-overlapping. This results in all subsequent triplets being altered. This means the subsequent protein formed from this gene is highly likely to be severely disrupted and the primary, secondary and tertiary protein structure will be severely altered, such a protein will thus not function correctly, if at all, and will be degraded in the cell.

  • -  Sometimes a triplet may be added or deleted but this results in the addition or removal of a single amino acid not a frameshift

  • -  A frameshift is particularly harmful in the middle or beginning of a gene as then the number of affected amino acids is far greater

  • -  There are also explaining triplet nucleotide repeats: this is where there is a repeating triplet (ATG, etc.) and at meiosis the number of repeats continually increases, this is the cause of Huntington's Disease

  • -  Mutations do not only have to be harmful, they may be beneficial and this is the basis for natural selection; or even neutral and have no real effect.

  • -  Regulation of gene control:

- Required as some genes will only be synthesised under specific conditions or environments while others will be synthesised at a standard rate

  • -  DNA also has introns and exons, introns are non–coding regions of DNA while exons are coding regions of DNA

  • -  It is important to understand that an operon is a group of genes which function as a transcription unit

  • -  Lac Operon Function:

    • -  Used in bacteria which would normally metabolise glucose but if glucose

      is absent they must still respire and so they can use lactose

    • -  Thus in the absence of glucose and presence of lactose 2 enzymes are

      synthesised

      • -  Lactose permease - enables lactose to get into bacterial cells

      • -  (also transfer acetylase which is a isomerase enzyme which

        converts galactose to glucose)

      • -  B-galactosidase - hydrolyses lactose to produce glucose and

        galactose

    • -  The lac operon (operon defined above) consists of a length of DNA with

      an operator region lacO next to two genes that are lacZ & lacY These two enzymes code for the 2 enzymes above (Z codes for galactosidase and Y for Lactose permease)

    • -  Next to the operator region is a promoter region P this is the site which RNA polymerase must bind to begin transcription (THINK: promoter promotes the binding of polymerase)

    • -  Further upstream of the Promoter region is a regulator gene I this codes for a repressor protein lacI for the operator region. This means that if the repressor protein is produced it will bind to lacO and prevent the transcription of the lacZ and lacY genes. This means that lactose cannot be metabolised as the genes are ‘off’

    • -  The above is facilitated as the repressor protein has a structure that is complementary to the operator region

    • -  In the presence of Lactose when all glucose has been used the lactose will bind to the repressor protein molecules (lacI) which causes a conformational change in the shape of the lacI protein and makes it no longer complementary to the operator and so it can no longer bind to the region, this means that the RNA polymerase can bind to the promoter region and transcribe the genes and thus synthesise the enzymes that are required to hydrolyse lactose and thus provide glucose for respiration

  • -  The lac operon and the above are only in prokaryotes, in Eukaryotes:

    • -  All the cells have the same genome but the basis of specialisation is that

      not all the genes are being expressed in all cells

    • -  They all share expression of common ‘housekeeping genes’

    • -  Gene expression is controlled by Transcription factors, these are short

      non-coding RNA that combines with a specific site on a length of DNA

      and inhibits or activates transcription of the gene or genes

    • -  A transcription factor will bind to its specific promoter gene

    • -  After binding they either aid or inhibit RNA polymerase binding

  • -  They are essential for the regulation of gene expression and regulating the cell cycle

  • -  An example: tumour suppressor genes and proto-oncogenes help regulate cell division and mutations can lead to cancer

- Post

  • -  Introns - non-coding, exons - coding

  • -  All DNA (intron or exon) is transcribed, the product is primary mRNA

  • -  This undergoes editing to remove the introns or the lengths of mRNA

    which correspond to the introns on the DNA

  • -  mRNA exons post processing are then joined together

  • -  This process may use the endonuclease enzyme

transcriptional gene regulation:

- Post

  • -  This involves the activation of proteins which can be through

    phosphorylation

  • -  It may also use the second messenger of cAMP (cyclic AMP)

    • -  Signalling molecule such as a protein binds to a receptor on the plasma cell membrane which is associated with a G protein

    • -  This binding activates the G protein

    • -  The G protein activated adenyl cyclase

    • -  Adenyl cyclase catalyses the formation of many molecules of

      cAMP from ATP

    • -  The cAMP activates PKA (protein kinase A)

    • -  PKA catalyses the phosphorylation of proteins which utilises ATP

      through hydrolysis of ATP, the phosphorylation then activates many enzymes in the cytoplasm

- These may be those that convert glycogen to glucose etc.

  • -  PKA can then phosphorylate another protein

  • -  This may then enter the nucleus and act as a transcription factor

- Genetic Control of Body Plan Development:

  • -  Homeotic genes are involved in controlling the anatomical

    development/morphogenesis of an organism so all structures develop correctly

  • -  These often contain homeobox sequences/homeobox genes (sequence involved in regulating the patterns of anatomical development in fungi, animals and plants

  • -  The length of the chain including only the introns is 180 DNA base pairs which codes for a 60 amino acid sequence that is known as a homeodomain sequence

  • -  This sequence can fold into shape and bind to DNA to regulate the transcription of adjacent genes and are thus transcriptional factors

  • -  The shape they form is called the H-T-H as it contains two alpha helixes and a turn inbetween it

  • -  Homeobox genes are very similar and are highly conserved

  • -  A subset of these is hox genes which are found only in animals

  • -  Molecular evidence shows that the homeobox genes were found in Cnidaria 541

    million years ago and shows they arose in early ancestors and have been conserved since then

Translational gene regulation:

  • -  The sequence is similar in all animals studied to date

  • -  Hox genes control which body parts grow where, in mutated hox genes there can

    be growth abnormalities

  • -  In early development the hox genes express from the anterior to the posterior

    axis of the embryo which is why we develop body parts in a given order and set

    structure

  • -  Some may also cause apoptosis etc.

  • -  Hox genes are regulated by Gap genes and pair rule genes which are in turn

    regulated by maternally supplied mRNA from the egg cytoplasm

- Mitosis and Apoptosis:

  • -  Mitosis is regulated with the help of hox genes and homeobox genes

  • -  Assures that each new daughter cell contains the full genome

  • -  Also responsible for switching genes off during differentiation

  • -  Cells will undergo mitosis about 50 times before dying this is the hayflick constant

  • -  Apoptosis - programmed cell death

    • -  Enzymes break down the cytoskeleton

    • -  Cytoplasm dense with tightly packed organelles

    • -  Cell surface membrane changes and small protrusions emerge called

      blebs

    • -  Chromatin condenses and the nuclear envelope breaks and DNA

      fragments

    • -  Cell breaks into fragments that are ingested by phagocytic cells so debris

      cannot damage other cells

  • -  Control:

    • -  Controlled by many cell signals which may be released due to internal stimuli such as stress

    • -  Signalling molecules such as cytokines are key as well as hormones growth factors, nitric oxide etc.

    • -  Nitric oxide acts to make the membrane more permeable to H+ ions which makes the proton gradient lessen

    • -  Equally proteins may bind to apoptosis inhibitor proteins allowing apoptosis to occur

  • -  Apoptosis is key in development for limb development and enabling digits to separate from each other

  • -  Apoptosis removes ineffective or harmful lymphocytes during immune development

  • -  The rate of cell death should be equal to the rate of cells produced, if it is more there will be cell loss and degeneration and if it is less then there will be tumours

    Homebox

  • -  Hormones that are lipid soluble act to enter the cell and bind to transcription factors

    which then are complementary to the promoter region and blood RNA polymerase

    binding and thus stopping the transcription

  • -  Homeobox genes are highly conserved as mutations in the are not advantageous

  • -  Hox and Homeobox often used interchangeably

  • -  Position along chromosome

    Gene therapy is to do with the transfer of an allele to a cell without the allele can be in transferred into an embryo (bad as disruption of embryo, unpredicted effects, embryo rights)

    Euchromatin vs Heterochromatin and to do with how heterochromatin is tightly wound while euchromatin is weakly bound

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