8. Control of Gene Expression

• A mutation is an alteration to the DNA base sequence
• Mutations often arise spontaneously during DNA replication
• Addition and deletion mutations involve the insertion or deletion of one or more nucleotides from the DNA sequence
• A substitution mutation is where one nucleotide in the DNA sequence is replaced by another
• A duplication mutation occurs when one or more nucleotides duplicate and repeat in the DNA sequence
• An inversion mutation is when a group of nucleotides become separated from the DNA sequence and then rejoin in the reverse order
• A translocation mutation is where a group of nucleotides become separated from the DNA sequence and are then inserted into the DNA of a different chromosome
• Insertion, deletion, duplication, and translocation mutations are most likely to have a significant impact because they produce a frameshift, altering the entire amino acid sequence
• Substitution and inversion mutations are less likely to have a significant impact because they only alter one or very few triplets, which might not affect the amino acid sequence due to the degenerate nature of the genetic code
• A mutation resulting in a change to the amino acid sequence is not always harmful; it may be neutral if the resulting change has no effect on the organism, or even beneficial, contributing to evolution and natural selection
• A mutagenic agent is a factor that increases the rate of gene mutation, examples include chemical mutagens like alcohol and benzene, as well as ionising radiation such as UV and x-ray
• Stem cell definition: Undifferentiated cells that can divide indefinitely and turn into other specific cell types
• Three types of stem cells:

  • Totipotent: can develop into any cell type including the placenta and embryo
  • Pluripotent: can develop into any cell type excluding the placenta and embryo
  • Multipotent: can only develop into a few different types of cell
• What happens to totipotent cells during embryonic development: Certain parts of the DNA are selectively translated so that only some genes are ‘switched on’, in order to differentiate the cell into a specific type and form the tissues that make up the foetus
• Unique feature of pluripotent cells and its use: They can divide in unlimited numbers, and can be used to repair or replace damaged tissue
• Unipotent cell definition and example: A cell that can only develop into one type of cell. An example is cardiomyocytes (heart cells)
• Types of stem cells found in embryos: Totipotent and pluripotent. Multipotent and unipotent cells are only found in mature mammals
• Uses of stem cells: Medical therapies (e.g. bone marrow transplants, treating blood disorders), drug testing on artificially grown tissues, research on formation of organs and embryos
• How induced pluripotent stem cells are produced: From mature, fully specialised (somatic) cells. The cell regains capacity to differentiate through the use of proteins, particularly transcription factors
• Transcription factor definition: A protein that controls the transcription of genes so that only certain parts of the DNA are expressed, allowing a cell to specialise
• How transcription factors work:

  • Move from the cytoplasm into nucleus
  • Bind to promoter region upstream of target gene
  • Makes it easier or more difficult for RNA polymerase to bind to gene, increasing or decreasing rate of transcription
• Example of a hormone affecting transcription and how it works: Steroid hormone oestrogen diffuses through cell membrane, forms hormone-receptor complex with ER α receptor in the cytoplasm, complex enters the nucleus & acts as a transcription factor to facilitate binding of RNA polymerase
• Epigenetics definition: A heritable change in gene function without change to the base sequence of DNA
• Effect of increased methylation of DNA on gene transcription: Addition of a CH3 group to cytosine bases next to guanine prevents transcription factors from binding, suppressing gene transcription
• Effect of decreased acetylation of histones on gene transcription: Positively-charged histones bind to negatively-charged DNA. Decreasing acetylation increases positive charge of histones, preventing transcription factors from accessing DNA and suppressing gene transcription
• How epigenetic changes can affect humans: Can cause disease by over activating a gene’s function (e.g. in cancer) or by suppressing it
• Application of epigenetics: Treatments of various diseases, development of ways to reverse epigenetic changes
• Process of RNA interference and organisms in which it occurs: RNA molecules inhibit gene expression by destroying mRNA, occurs in eukaryotes and some prokaryotes
• Characteristics of benign tumours:

  • Slow growth
  • Defined by a clear boundary due to cell adhesion molecules
  • Cells retain function and normal shape
  • Don’t spread easily
  • Easy to treat
• Characteristics of malignant tumours:

  • Rapid, uncontrollable growth
  • Ill-defined boundary (finger-like projections)
  • Cells do not retain function and often die
  • Spreads quickly and easily (metastasis)
  • Difficult to treat
• Role of tumour-suppressor genes: Code for proteins that control cell division, stop the cell cycle when damage is detected, and are involved in programming apoptosis (‘self destruction’ of the cell)
• The genome is the complete set of genetic information contained in the cells of an organism
• How tumour-suppressor genes can be involved in developing cancer: Mutation in the gene could code for a nonfunctional protein, increased methylation or decreased acetylation could prevent transcription, leading to uncontrolled cell division and tumour formation
• Role of proto-oncogenes: Control cell division, code for proteins that stimulate cell division
• Genome sequencing is identifying the DNA base sequence of an individual, allowing us to determine the amino acid sequence of the polypeptides coded for by that DNA
• The proteome is the complete set of proteins that can be produced by a cell
• In simple organisms, the genome can be directly translated into the proteome, but in complex organisms, it is harder due to non-coding DNA and regulatory genes
• How proto-oncogenes can be involved in developing cancer: Mutation in the gene could turn it into a permanently activated oncogene, decreased methylation or increased acetylation can cause excess transcription, resulting in uncontrolled cell division and tumour formation
• An application of sequencing the proteome in simple organisms is identifying potential antigens for use in vaccine production
• Applications of genome sequencing include:

  • Comparing genomes between species to determine evolutionary relationships
  • Genetic matching
  • Personalised medicine
  • Synthetic biology