Genetics of Living systems

• mutation - change in sequence of bases in DNA; caused by substitution, deletion or insertion of a nucleotide within a gene
• the position and involvement of the amino acid in the R group interactions within the protein will determine the impact of the new amino acid on the function of the protein
• frameshift mutation - 1 or more nucleotides are added or deleted from the 3' end of the gene
• effect of different mutations:

  • no effect - there is no effect on the phenotype of an organism because normally functioning proteins are still synthesised
  • damaging - the phenotype of an organism is affected in a negative way because proteins are no longer synthesised or is non-functional
  • beneficial - protein synthesised results in a useful characteristic
• mutagens - chemical, physical or biological agent which causes mutations
• chromosome mutations affect the whole chromosome
• genes can be regulated by:

  • transcriptional control - genes can be turned on or off
  • post-transcriptional - mRNA is modified
  • translational - translation can be stopped or started
  • post-translational - proteins can be modified after synthesis which changes their functions
• heterochromatin - tightly wound DNA causing chromosomes to be visible during cell division, transcription is not possible
• euchromatin - loosely wound DNA present during interphase
• chromatin regulation prevents the complex and energy-consuming process of protein synthesis from occurring when cells are actually dividing
• histone modification - DNA coils around histones because they are positively charged and DNA is negatively charged. histones can be modified to increase or decrease the degree of packing
• acetylation - acetyl groups added to lysine residues making them more negative so less likely to bind with DNA
• methylation - methyl group added to cytosines in CpG islands (regulatory regions) making it harder for RNA polymerase to attach
• DNA methylation occurs at specific sites within the genome and is heritable through mitosis but not meiosis
• Lac operon:

  • an operon is a group of genes that are under the control of the same regulatory mechanism and are expressed at the same time
  • lac operon is a group of lacZ, lacY and lacA genes which code for enzymes
  • a regulatory gene is located near to the operon and codes for a repressor protein that prevents the transcription of the structural genes in the absence of lactose
• when no lactose is present:

  • the repressor protein binds to the operator region and covers part of the promoter region
  • this prevents the transcription of the structural genes as RNA polymerase cannot bind to the promoter region
  • the repressor protein is constantly produced
• when lactose is present:

  • lactose binds to the repressor protein causing it to change shape
  • thus it can no longer bind to the operator
  • RNA polymerase can now bind to the promoter so the structural genes are transcribed
• CAP and cAMP:

  • RNA polymerase alone does not bind well to the lac operon
  • CAP binds to a region of DNA before the lac operon and helps RNA polymerase attach to the promoter
  • CAP is regulated by cAMP which is a "hunger signal" made by E. coli when glucose levels are low
  • cAMP binds to CAP, changing its shape and making it able to bind to DNA
  • CAP is only active when glucose levels are low
• RNA processing:

  • transcription produces a precursor molecule known as pre-mRNA
  • this is modified to produce mature RNA
• RNA modification:

  • a cap is added to the 5' end and a tail to the 3' end
  • cap - modified nucleotide
  • tail - chain of adenines
  • this stabilises mRNA and delays degradation
  • it will last longer and more protein can be synthesised from it
  • the cap aids the binding of ribosomes to mRNA
  • the mRNA is also spliced
  • introns are removed and exons are joined together
• RNA editing:

  • the sequence of nucleotides can be modified by base addition, deletion or substitution
  • this causes the same results as point mutations
  • this increases the range of proteins produced from a single gene
• protein synthesis can be controlled by:

  • degradation of mRNA
  • binding of inhibitory proteins
  • activation of initiation factors which aid the binding of mRNA to ribosomes
• post-translational control:

  • some proteins are not functional straight after they have been synthesised and therefore need to be activated tow ork
  • this can include addition of non-protein groups, modification of amino acids, folding of proteins or modification by cAMP
• example of cAMP:

  • glucagon binds to receptor
  • this activates a transmembrane protein which activates a G protein
  • the G protein activates adenylyl cyclase which converts ATP to cAMP
  • cAMP activates PKA which catalyses the phosphorylation of various proteins which thus activates enzymes in the cytoplasm
• Protein kinases:

  • enzymes that catalyse the addition of phosphate structure groups to proteins
  • this changes the tertiary structure and function of the protein
  • cell activity can be controlled using kinases
• morphogenesis - the regulated pattern of anatomical development
• Homeobox genes - a group of genes which contain a homeobox
• homeobox - section of DNA 180 base pairs long coding for a part of the protein 60 amino acids long that is highly conserved in plants, animals and fungi. This part of the protein binds to DNA and switches other genes on or off
• Hox genes:

  • one group of homeobox genes present in animals
  • responsible for the correct positioning of body parts
  • found in gene clusters
  • the order in which they appear along the chromosome is the order in which the effects are expressed in the organism
• somites - segments in the embryo which are directed by Hox genes to develop in a particular way.
• symmetry:

  • most animals show symmetry
  • radial: top and bottom
  • bilateral: right and left side, head and tail
  • diploblastic: body derived from two embryonic cell layers
  • triploblastic: body derived from three embryonic cell layers
• mitosis:

  • regulated with the help of homeobox and Hox genes
  • normal body cells divide around 50 times before death
• apoptosis:

  • cytokines, hormones, growth factors and nitric oxide can induce apoptosis
  • proteins are released into the cytoplasm that will bind to apoptosis inhibitor proteins
  • apoptosis is an integral part of plant and animal development
  • extensive proliferation of cell types is prevented by apoptosis
  • apoptosis removes harmful T lymphocytes
  • not enough causes tumours, too much causes cell loss