Bio 2.7

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Bio 2.7

• Gene Expression

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Proteins
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Actin 374 amino acids
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The human insulin protein is composed of 51 amino
acids, It is a dimer of an A-chain and a
B-chain, which are linked together by disulfide
bonds.
The largest known proteins are the titins, a
component of the muscle sarcomere, with a
molecular mass of almost 3,000 kDa and a total
length of almost 27,000 amino acids.
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Protein Synthesis
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• DNA
• ATG CGT GCA ATG TTT ACG CGT TGA TAC GCA CGT TAC A
  AA TGC GCA ACT mRNA
• AUG CGU GCA AUG UUU ACG CGU UGA
• Protein

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DNA vs RNA

• Bases
• Strands
• Length
• Sugar
• Location
• longevity

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Degeneracy Redundancy

• Degeneracy occurs in biology when dissimilar
  structures carry out the same job. In protein
  synthesis the genetic code shows degeneracy
  because of the fact that several different codons
  code for the same amino acid.
• Redundancy refers to situations where structures
  are unneeded or unnecessarily repeated. Because
  the genetic code is degenerate it also becomes
  partly redundant we dont need 6 codons for
  isoleucine, one would suffice
• Why is redundancy retained?
• If an error occurs in transcription and the wrong
  base is inserted then there is a chance that the
  correct amino acid is still put in and the
  protein will still function normally. Eg mutation
  of CUU to CUC still results in the amino acid leu
  (this is sometimes called third base wobble

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Consider

• What would be the consequences if RNA polymerase
  was inhibited?
• Class Ideas 2013
• - Lowered rate of transcription b/c RNA
  polymerase is necessary to match complementary
  RNA nucleotides with the template DNA in order to
  produce mRNA. Lack of mRNA means less
  translation, less polypeptide, less protein. Less
  protein is important because proteins such as
  haemoglobin are necessary for life (haemoglobin
  transports the oxygen required in
  respiration.add other structural protein
  examples and functional examples especially
  enzymes in order to secure the grade at the E
  level)

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Metabolic Pathways
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Metabolic Pathways

• Metabolism complete set of chemical reactions
  necessary for life.
• Metabolic Pathway A sequence of chemical
  reactions that lead from some precursor to a
  product,
• product of each reaction is starting material for
  the next
• Metabolite reactants, intermediates, and
  products
• gt 2000 known metabolic reactions, each catalyzed
  by a distinct enzyme
• anabolic pathway building a complex molecule
• catabolic pathway complex molecule ? simpler
  molecule

Final phenotype (physical appearance) of an
organism is determined by the presence, absence
or exact amount of each metabolic product
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• Insert BZ simple pathway here

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Catabolic Metabolism of Phenylalanine

• One of the most well known metabolic pathways
• Phenylalanine is an essential amino acid
  (obtained in the diet, not made by the body)
• It is normally catabolised into a range of
  substances including the skin pigment melanin
• Deficiencies in enzymes controlling the reactions
  this can lead to build up of poisonous
  metabolites (causing a range of syndromes) and/or
  failure to complete some processes eg no melanin
  albinism

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Phenyalanine Metabolism Simple Version
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Ammonia is a toxic waste product of metabolism.
It is converted into the less toxic waste product
urea via the urea cycle
The end product in a metabolic cycle becomes the
starting product so that the cycle can repeat. Eg
in the urea cycle ornithine is the end product
and becomes the start product so that more
ammonia can be broken down
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Mutations
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Mutations

• A mutation is a change in DNA that is not
  immediately and properly repaired. Mutations
  occur spontaneously 1 per 106 108 cell
  divisions.
• Mutations are usually recessive and usually
  harmful e.g. CF, sickle cell disease.
• Some mutations beneficial, e.g. the population in
  Limone in Italy has a high tolerance to high
  cholesterol.
• Some mutations are neutral (or silent),
  especially those that do not alter the amino acid
  sequence.
• A mutation in a body cell ? cancer, cell death.
• A mutation in a germ cell ? offspring with a
  mutation.
• A mutation in a zygote cell ? chimaera, some
  cells express the mutation, others dont.

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Mutagens Carcinogens

• Mutagens increase the rate of mutations.
• Carcinogens cause cancer.
• Mutagens include
• ionising radiation
• UV rays
• X-rays
• chemicals, e.g. benzene, asbestos, tobacco tar
• viruses and microorganisms, e.g. HIV, hepatitis B
• ethanol/diet, e.g. high fat diet.

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Beneficial Human Mutations

• Lactase persistence
• more listed here

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Beneficial Mutation Example

• Tolerance to high cholesterol levelsin humans
• In the small village of Limone, about 40
  villagers have extraordinarily high levels of
  blood cholesterol, with no apparent harmful
  effects on their coronary arteries.
• The village has a populationof 980 inhabitants
  and was,until recently, largely isolatedfrom
  the rest of the world, withsheer cliffs behind
  the village,the lake in front of them,and no
  road access.

The village of Limone, on the shore of Lake
Garda, Italy
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Beneficial Mutation Example

• The 40 villagers possess a point mutation which
  alters the protein produced by just one amino
  acid. This protein is ten times more effective at
  mopping up excess cholesterol.
• No matter how much excess cholesterol is
  ingested, it can always be disposed of.
• All carriers of the mutation are related and have
  descended from one couple who arrived in Limone
  in 1636.
• Generally, the people of Limonelive longer and
  show a highresistance to heart disease.

High blood cholesterol and dietary fat are
implicated in the formation of plaques in the
coronary arteries and in the development of
cardiovascular disease.
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Single Gene Mutations(aka point mutations)

• Substitution is when one base is replaced by
  another. Missense substitutions result in the
  wrong a.a. Nonsense substitutions result in a
  stop codon.
• Insertion is when one base is inserted.
• Deletion is when one base is removed.
• Inversion is when the order of 2 bases is
  swapped.
• A point mutation is a mutation in a single
  nucleotide or change to a triplet.
• A reading frame shift can be the result of an
  insertion, deletion, or both (a partial reading
  frame shift).
• E.g. Sickle cell disease single substitution of
  T?A in the b chain of the Hb protein (HBB) on
  chromosome 11. The protein precipitates in low O2
  conditions, resulting in the sickle shape of the
  RBCs.

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Iron Toxicity

• The therapeutic dose for iron deficiency anaemia
  is 36 mg/kg/day. Toxic effects begin to occur at
  doses above 1020 mg/kg of elemental iron.
  Ingestions of more than 50 mg/kg of elemental
  iron are associated with severe toxicity
• Approximately 3 grams is lethal for a 2 year old
• Symptoms
• The first indication of iron poisoning by
  ingestion is a pain in the stomach, as the
  stomach lining becomes ulcerated. This is
  accompanied by nausea and vomiting. The pain then
  abates for 24 hours as the iron passes deeper
  into the body and damages internal organs,
  particularly the brain and the liver, and
  metabolic acidosis develops. The body goes into
  shock and death from liver failure.
• Treatment
• Later stage treatment consists of cleaning the
  iron from the blood, using a chelating agent such
  as deferoxamine. If this fails then dialysis is
  the next step.

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Weet bix

• How much weet bix would kill you? (from iron
  toxicity)
• 2 year old lethal dose 3g
• Iron per weetbix 1.5mg (0.0015g).
• Dose 3/0.0015 2000 weet-bix
• 70kg Adult Severe toxicity _at_ 50mg/kg
• Dose (50 x 70) / 0.0015 2.3 million weet bix

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Cystic Fibrosis

• Inherited genetic disease symptoms include
  excess mucous production in lungs, gut
• Prevents pancreatic enzymes reaching small
  intestine.
• SOLUTION?
• Lungs coughing
• Gut Oral enzymes
• SOURCE?
• Pigs
• more issues

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Cause The cystic fibrosis transmembrane
conductance regulator (CFTR) gene is found at the
q31.2 locus of chromosome 7, is 230,000 base
pairs long, and creates a protein that is 1,480
amino acids long. The product of this gene (the
CFTR) is a chloride ion channel important in
creating sweat, digestive juices and mucus. The
most common mutation, ?F508, is a deletion (?) of
three nucleotides38 that results in a loss of
the amino acid phenylalanine (F) at the 508th
position on the protein. This mutation accounts
for two-thirds (66-7016) of CF cases worldwide
and 90 of cases in the United States however,
there are over 1500 other mutations that can
produce CF. Although most people have two
working copies (alleles) of the CFTR gene, only
one is needed to prevent cystic fibrosis. CF
develops when neither allele can produce a
functional CFTR protein. Thus, CF is considered
an autosomal recessive disease.
http//en.wikipedia.org/wiki/Cystic_fibrosisManag
ement
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Gene Environment Interactions

• The ultimate expression of genes (phenotype) is a
  combination of the genotype (genetic potential)
  and the effects of the external environment
  (abiotic and biotic factors).
• How might the following affect an organism?
• food and water availability
• pH
• light
• altitude
• temperature
• presence of other organisms of the same species
• predation (in daphnia..next slide)

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Examples
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Ceriodaphnia 40x, 2x digital 'good' image Note,
though the image is a similar size, this is a
much larger species
Ceriodaphnia 100x, 2x digital 'good' image
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Resting egg pouch (ephippium) and the juvenile
daphnid that just hatched from it
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