gene expression

• a gene mutation is changes to the base sequence or quantity of DNA within a gene or section of DNA
• mutations can be small scale gene mutations occurring spontaneously during mitosis. Or large scale chromosome mutations that typically occur during meiosis
• If mutations occur during gamete formation that may be inherited by offspring, increasing genetic variation within a species, which is important for evolution.
• if mutations occur during mitosis of somatic cells they are not inherited by offspring, but may result in cancer
• There are three main types of gene mutations: substitution ( nucleotide is replaced by a different nucleotide). insertion ( the addition of one or more nucleotides into the DNA sequence ). deletion ( the removal of one or more nucleotides from the DNA sequence)
• substitution mutation: a single substitution mutation changes the base sequence of the DNA strand, altering the codon that the nucleotide is present in. This has 3 possible consequences. Formation of a premature stop codon, resulting in a very short polypeptide that can't function properly. The codon codes for a different amino acid, resulting in a polypeptide differing one amino acid. The proteins function may be affected. or the codon codes for the same amino acid, due to the degenerate nature of the genetic code.
• insertion and deletion mutations: Both of these mutations result in a frame shift (where the reading frame for the decoding of DNA moves) This results in a change to every successive codon from the point of insertion/deletion. This can cause a large change to the amino acid sequence and resulting protein, with an indel mutation near the beginning vastly altering the protein phenotype and one nearer the end having a smaller impact. If three nucleotides are added or removed in sequence, then the frame does not shift, with the only difference being the addition or subtraction of one amino acid
• Inversion mutations involved a sequence of bases being separated and then reattached in the inverse order. They change the codons in the mutated area, affecting several amino acids in the polypeptide
• duplication mutations: one or multiple bases are repeated, this can result in frame shift altering every codon from that point and significantly affecting the polypeptide formed
• mutations may occur spontaneously during DNA replication, with a rate of around one in a hundred million bases. This rate is increased by mutagenic agents (chemical, biological or physical agent that causes mutations). Mutagens include high energy ionising radiation, chemical agents that react with DNA, and biological agents like viruses that insert their own dna. Many mutagens cause mutations in cells that lead to the cell becoming cancerous, these are known as carcinogens
• some mutations don't affect protein structure. This is as the mutation may occur in an intron, or result in a codon coding for the same amino acid as the genetic code is degenerate (silent mutation). Some mutations will cause changes to the protein, altering the primary structure and therefore the bonds that form the secondary and tertiary structure. changing the polypeptides specific shape
• protein function and structure can be only slightly impacted by a mutation, remaining functional, if a substitution results in only one differing amino acid, with similar properties to the original (conservative mutation). Protein structure and function may be significantly impacted if the changed amino acid has different properties, it is located in an important part of the protein like the active site, or its a frame shift mutation where many amino acids are changed.
• polyploidy is a chromosome mutation that happens when there are an extra set of chromosomes in a cell. wheat evolved through polyploidy, starting out with a 2n chromosome number, and ending up with 6n
• non-disjunction is a chromosome mutation where a single chromosome is included or excluded. It happens in meiosis if a homologous pair fail to separate. Leaving one gamete with an extra chromosome and the other without one. If one of these gametes fuses during fertilisation, the zygote will have an extra or missing chromosome. This causes Down syndrome if you have an extra chromosome 21
• translocations can occur when a piece of DNA snaps off and doesn't reattach to itself or the homologous pair. This can be a balanced swap where DNA swaps between chromosomes. This is not always harmful as the cell still has all the DNA it needs. But in unbalanced translocations a piece of DNA from one chromosome replaces a piece from another. One chromosome has therefore lost some DNA and there are genes the cell can't transcribe this can be harmful as genes are lost altogether from chromosomes. translocations between chromosome 8 and 21 can cause leukaemia, interfering with genes.
• Totipotent stem cells can divide by mitosis and produce any type of body cell. They begin in early mammalian embryos as unspecialised cells, as they develop only part of the genome is expressed and the cells differentiate into specialised cells
• cell differentiation is the process by which a cell becomes specialised for different functions
• cell specialisation is the process where cells develop specific functions and structures in order to carry out specific tasks within an organism
• every cell in the body contains the same genome with all genes, but specialised cells only express a small subset of genes relating to their function. With only a fraction of the proteins possible to produce being produced by each cell. This expression of genes can be stopped by stopping mRNA production or stopping translation of mRNA
• totipotent stem cells - pluripotent stem cells - multipotent stem cells - unipotent stem cells
• totipotent stem cells can differentiate into any type of cell. When they divide they produce another copy of them selves via self renewal. They are only found in mammalian embryos for the first few divisions before they become differentiated
• pluripotent stem cells can differentiate into almost any type of cell, except the placenta cells. They include embryonic and foetal stem cells
• multipotent stem cells can only differentiate into a limited number of cell types, they are found in the umbilical cord and adult stem cells
• unipotent stem cells are derived from multipotent cells and can only differentiate into a single type of cell. They are made in adult tissue and include cardiomyoblasts which can only differentiate into cardiomyocytes
• in mammals stem cells can be found in different places, in differing stages of development. embryonic stem cells come from early embryos and are pluripotent. stem cells from the umbilical cord blood are multipotent. Adult stem cells are found in many tissue types in the adult and foetus. They are multipotent and can differentiate into a small number of cell types to replace damaged cells.
• pluripotent stem cells are useful in medicine for treating type 1 diabetes, degenerative disorders and blood diseases. As well as for research, but obtaining them from embryos is ethically challenging.
• induced pluripotent stem cells: unipotent stem cells that have been reprogrammed to become pluripotent
• producing induced pluripotent stem cells: embryonic stem cells are pluripotent as they can express genes for transcription factors associated with pluripotency. This allows the stem cell to self renew and differentiate into any cell type. These genes stop being expressed when the cell differentiates into an adult cell, but a unipotent stem cell can be induced to an ips when these genes are switched back on
• embryonic stem cell use: for - undifferentiated ball of cells that does not represent a human life. Prevent human suffering. Embryos can be destroyed after fertility treatments, not consistent to ban it for research. against: could become human foetus when implanted in the womb. some believe embryos have a right to life. fears may lead to human reproductive cloning
• pluripotent stem cells can be used to regrow damaged tissues , b cells of the pancreas can treat type 1 diabetes. nerve cells could be used to treat parkinsons disease, strokes, alzheimers, or paralysis. blood cells can treat leukamia, retina cells can treat macular degeneration.
• controlling expression of a gene: for transcription to begin the gene is switched on by transcription factors moving from the cytoplasm to the nucleus. each transcription factor has a site that binds to specific base sequence of the DNA sequence. When it binds it causes that region of DNA to begin the transcription process. mRNA produced is translated into a polypeptide. When a gene is not expressed the site on the transcriptional factor that binds to DNA is not active. As the site on the transcriptional factor binding to DNA is inactive and cannot cause transcription and polypeptide synthesis
• oestrogen is a lipid soluble molecule that diffuses easily through the phospholipid bilayer of the cell surface membrane. Once inside the cell, oestrogen binds with the site of a receptor molecule on a transcriptional factor. binding of oestrogen to the transcription factor alters the shape of its DNA binding site, activating it so it can bind to DNA. transcriptional factor can now enter the nucleus through a nuclear pore, and bind to a specific DNA base sequence. combining of transcriptional factor with DNA stimulates transcription of the gene.
• epigenetics is the changes in DNA that alter the expression of genes, without changing the base sequence of DNA itself
• Epigenetic changes, unlike mutations, do not alter the base sequence of DNA. Chemical tags are added onto the DNA and histones, with the chemical tags forming a second layer known as the epigenome. the epigenome determines the shape of the DNA-histone complex. This keeps inactive genes tightly packed, so they can't be read - epigenetic silencing. The epigenome is flexible as chemical tags respond to the environmental changes. The epigenome of a cell is the accumulation of signals recieved during its lifetime, acting like cellular memory
• Initially the epigenetic signals come from the mothers nutrition and foetal cells. After birth hormones, diet, stress levels all affect the epigenome
• Epigenetic factors can lead to the acetylation of histones leading to the activation or inhibition of a gene. Or the methylation of DNA by attracting enzymes that can add or remove methyl groups.
• When the association of histones with DNA is weak, the DNA-histone complex is less condensed, so the DNA is accessible by transcription factors that can initiate mRNA production. When the association is stronger the DNA-histone complex is more condensed. So is not accessible by transcription factors, so production of mRNA cannot be produced and the gene is switched off. Condensation of the DNA-histone complex therefore inhibits transcription and can be achieved by decreased acetylation of histones or increased methylation of DNA
• decreased acetylation of histones: acetylation is the process by which an acetyl group is transferred to a molecule. Here the acetyl donor is acetyl coenzyme A. (deacetylation is the reverse). decreased acetylation increases the positive charges on histones and increases the attraction to DNA phosphate groups. So the DNA-Histone complex is more closely associated, and the DNA is not accessible to transcription factors. These transcription factors can't initiate mRNA production from DNA, so the gene is switched off
• increased methylation of DNA: methylation is the addition of a methyl group to a molecule. In this case the methyl group is added to the cytosine bases of DNA, it normally inhibits transcription of genes in 2 ways. Preventing the binding of transcriptional factors to the DNA. Or attracting proteins that condense the DNA-histone complex by inducing deacetylation of the histones, making DNA inaccesible to transcription factors.
• small interfering RNA is a small double stranded RNA molecule, which binds to mRNA transcribed from target genes as their base sequence is complementary. Each siRNA is attached to a protein complex which is able to breakdown the mRNA that has been transcribed from target genes, so the mRNA is unable to be translated into proteins