Gene Expression

• Polypeptide Chain Protein

  • Some proteins consist of one polypeptide chain into a 3D shape.
  • Some proteins contain multiple polypeptides linked together.
  • Poly = many. Peptide = proteins.
• Protein Synthesis Outline

  DNA

  • Transcription (nucleus)

  pre-mRNA

  • Splicing

  mature mRNA

  • Translation (ribosomes)

  polypeptide chain of protein
• Cell Differentiation

  • Once a zygote has developed into a gastrula, it then develops into different types of specialised cells.
  • This is shown on the image on the right.
  • Every somatic cell (all cells except sperm and egg) contains all genetic information to carry out every function.
• Cell Differentiation

  • Cell differentiation is the process where unspecialised stem cells (a blank cell) changes to a specialised cell.
  • The new cell has a specific structure and specialised function.
  • There are roughly 230 types of specialised cells in humans.
• Phenotype

  • Sister chromosomes (chromatids that contain same size, genes, etc.) control the phenotypic characteristics – the physical characteristics expressed from genes within an organism.
  • A pair of these (e.g. after cell replication) is referred to as a homologous chromosome pair.
• Alleles

  • Genes that are on corresponding pairs of chromosomes are known as alleles.
  • This makes up an organisms genotype.
  • Alleles are alternative forms of the same gene, and will express certain characteristics based on dominant and recessive genes.
  • This will result in different physical characteristics.
  • Different genes (alleles) appear due to mutations in the DNA in genes (covering later).
• Cell Differentiation

  • Specialised cells contain epigenetic tags.
  • These help activate and silence (turn on and off) specific genes in the cell.
  • This allows stem cells to become specialised cells. E.g. muscle cells or red blood cells.
  • Epigenetic tags are passed down during mitosis (cell division). This ensures daughter cells contain the same information to make the correct cells.
• Environmental Factors

  • It’s also suggested that environmental factors of an organism also influence the physical characteristics displayed by the organism.
  • Therefore, the relationship between phenotype and genotype can be expressed as:
  • P=G+E
  • P = phenotype
  • G = genotype
  • E = environment
• Stem Cells

  There's two main type of Stem Cells

  Multipotent

  • Can develop into some cell types only
  • Are more limited than pluripotent
  • E.g. stem cell that can only develop into different blood cells (red, white, platelets)
  • Are generally adult stem cells

  Pluripotent

  • Have potential to develop into any human cell
  • Are generally embryonic stem cells
  • Scientists have developed techniques to make multipotent stem cells act more like pluripotent, but this is still developing (induced pluripotent stem cells)
• Stem Cells

  • Therefore, stem cells are unspecialised and can differentiate into all specialised cells.
  • This makes up all tissues and organs in an organism.
  • Cell differentiation results from the regulation of gene expression.
  • Essentially some cells will have the ability to turn genes “on or off”.
  • All cells will have some genes always turned on. These are referred to as house keeping genes which are involved in general maintenance and energy provisions of the cell.
• Stem Cells

  Scientists are beginning to understand the exact signals that are involved in determining why cells in different regions and positions, develop differently.

  • Signal molecules released from one cell bind to the surface cell receptors on target cells. These signals may act as regulators of genes in the target cells nucleus.
  • Interaction of membrane proteins on cells may initiate signal molecules.
• Epigenetics

  • Epigenetics is the study of how external factors affect gene expression.
  • These are generally due to environmental factors.
  • Our DNA develops ‘chemical tags’ called collectively epigenome.
  • The chemical tags don’t affect the DNA base sequence (A, C, G, T), but change how cells are able to read the DNA and express specific genes.
  • Two main types of chemical tags:
  • Methylation of cytosine bases.
  • Acetylation of histone proteins.
• Factors Controlling Transcription

  • Gene expression is regulated by a range of cellular processes. Genes can be “switched on”, causing transcription, or “switched off”, preventing transcription from occurring.
  • Some genes are always switched on while others turn on and off.
• Factors Controlling Transcription

  Factors that control transcription are:

  • Transcription factors – promoter sequence (proteins) which will start or prevent transcription (assist/hinder RNA polymerase binding).
  • Methylation of cytosine bases – a methyl group (CH3) group is added to DNA strand, usually the cytosine nitrogenous base. Inhibits (stops) RNA polymerase from binding to DNA.
  • Histone modification – acetylation of histone proteins will decondense (loosen) DNA, making easier to transcribe. Deacetylation will coil DNA tighter (condense), making transcription more difficult.
• Epigenetics

  • Is the reason as to why identical twins can grow up and be vastly different.
  • Twins will be genetically identical but epigenetically different.
  • Same with clones.
  • Some epigenetic tags are now thought to be passed down from parents to offspring, affecting their growth and development.
  • Can affect an organism for its life, or be temporary.
  • Can lead to disease.
  • Can be affected by diet, chemical exposure and medication.
• Factors Controlling Translation

  • Multicellular organisms require many copies of the same protein.
  • Translated mRNA can be translated by multiple ribosomes to produce polypeptides or proteins in bulk.
  • Ribosomes will continue to translate (read) the mRNA until a signal to stop is provided.
  • There are other translation factors which can coordinate the synthesis or polypeptides and proteins. Three examples (there are many more) are:
  • Small interfering RNA (siRNA)
  • Long non-coding RNA (lncRNA)
  • Micro RNA (miRNA)
• Factors controlling translation

  Micro RNA (miRNA)

  • Small non-coding RNA molecules consisting of 22 nucleotides.
  • Will help regulate gene expression after transcription.
  • Will bind to a base of the mRNA, preventing ribosome from accessing the mRNA.

  Small interfering RNA (siRNA)

  • Known as silencing specific RNA that prevent translation of mRNA.
  • Similar size to micro RNA (21 nucleotides in size).
  • Will bind to mRNA
• Factors controlling translation

  • Long non-coding RNA (lncRNA)
  • lncRNA has many functions on controlling gene expression.
  • Focus here is its role as a translation factor.
  • Longer than miRNA and siRNA – about 200 nucleotides.
  • lncRNA will generally bind to miRNA, which prevents miRNA from inhibiting mRNA.
  • This promotes and increases translation.
• Factors Influencing Gene Expression

  • Phenotype (physical observable traits) is affected by an individuals genotype and the environment conditions its exposed to over its life.
  • Some factors that are known to influence gene expression:
  • Gender
  • Some genes are expressed differently in males than females. The hormones testosterone and dihydro testosterone are responsible for male pattern baldness. Dihydro testosterone will shrink hair follicles.
• Factors Influencing Gene Expression

  Chemicals

  • Many chemicals can interfere with gene expression, including illicit drugs, arsenics, methyl mercury and benzene.
  • One particular drug (thalidomide) was used in 1950’s and 60’s to combat morning sickness. However, thalidomide affected gene expression of arm and/or leg development.
• Factors Influencing Gene Expression

  Temperature

  • Some genes are expressed differently due to different temperatures.
  • Rabbit in Himalayas has a gene active between 15-25 degrees Celsius. This gene causes the white rabbit to have fur turn black.
  • Similar to UV light in skin cells in humans producing melanin.
• Factors Influencing Gene Expression

  Diet and lifestyle

  • Diet plays many roles in gene expression. Some are immediate while others are longer lasting.
  • An example is consuming lots of sugar, producing large amounts of the hormone insulin.
• Factors Influencing Gene Expression

  Trauma

  • Studies show that epigenetic trauma tags can be passed down.
  • Examples are holocaust survivors offspring and release of stress hormones.
• Epigenetic Changes and Disease

  • Many diseases linked to epigenetic changes to DNA and histones, such as cancer, cardiovascular disease, some auto-immune diseases.
  • Studies suggest environmental factors such as diet, stress, exposure to cigarette smoke, heavy metals and other chemicals may change patterns in DNA methylation, and healthy gene expression.
  • Cancer is caused by uncontrolled cell division. Genes associated with cell division are highly regulated/controlled. Epigenetic factors can affect the expression of these genes, causing uncontrolled cell division.
• Genes Associated with Cell Division

  Proto-oncogenes

  • Proto-oncogenes normally code for proteins involved in promoting cell division
  • Decreased methylation to DNA can therefore promote cell division and if uncontrolled, lead to the formation of cancers
• Genes Associated with Cell Division

  Tumour Suppression Genes

  • Under normal circumstances, these genes code for proteins that suppress or inhibit cell division
  • This helps keep the number of new cells in a tissue 'in check' and suppresses tumour formation
  • Increased DNA methylation of tumour suppression genes switches them off and the proteins suppressing tumour formation can no longer be produced (or in much small amounts)
  • As a result, uncontrolled division and a tumour could develop due to lack of normal cell division suppression.
• Genes Associated with Cell Division

  DNA Repair Genes

  • DNA repair genes can be activated to produce proteins involved in the repair of damaged DNA
  • Increased methylation to DNA repair genes would result in them being turned off. Consequently, less damaged DNA would be repaired, and damaged DNA would accumulate
  • This increases the risk of uncontrolled cell division and cancer developing
• Stem Cells

  Three main types of stem cells:

  • Embryonic stem cells – extraction of leftover fertilised ovum (pre-fetus).
  • Adult stem cells – extracted from areas such as bone marrow and umbilical cord.
  • Induced pluripotent stem cells (IPS cells) – methods to try to reprogram stem cells (e.g. skin cells or blood cells) in ways to make it become like a stem cell again.
• Therapeutic Cloning

  • The use of unspecialised stem cells.
  • Scientists use different techniques to control gene expression, and therefore the type of specialised cell it will differentiate into.
  • Scientists are able to replaced damaged or diseased cells, with healthy ones due to this.
  • There are limitations: injecting stem cells into someone can cause:
  • Rejection of stem cells
  • Development of wrong tissue type
  • Tumour formation.