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C7 > 1. DNA, RNA, Proteins and Evolution > Flashcards

1. DNA, RNA, Proteins and Evolution Flashcards

1
Q

word for when genes are on the same chromosome

A

correlated

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2
Q

what is the genetic crossover hypothesis?

A

traits that are usually linked are sometimes not inherited together because the chromosome pairs have wrapped around each other during meiosis

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3
Q

the probability of a radiation induced mutation is proportional to…

A

the density of ions produced by the radiation

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4
Q

chargaff’s rule =

A

DNA contains a 1:1 ratio of adenine:thymine and cytosine:guanine

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5
Q

what’s the difference between DNA and RNA sugar backbone?

A

DNA has a ribose sugar (with an OH) whilst RNA has a deoxyribose (with an H)

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6
Q

which position in the sugar is the base attached to?

A

1’

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7
Q

what holds DNA/RNA together

A

H bonds between bases.
van der waals forces
hydrophobic interactions

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8
Q

what is replication?

A

Making DNA from DNA

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9
Q

what is transcription?

A

making RNA from DNA

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10
Q

What is translation?

A

Making proteins from RNA

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11
Q

How many base pairs in human genome?

A

3x10^9

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12
Q

How many genes in human genome?

A

30,000

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13
Q

How many amino acids in average protein?

A

300

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14
Q

How many times shorter is a chromosome than the extended DNA?

A

10,000

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15
Q

DNA replication is catalysed by…

A

DNA polymerase

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16
Q

What is a primer?

A

A strand of DNA with a free 3’-OH group already bound to the template. DNA polymerase needs a primer to begin replication, but RNA polymerase does not.

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17
Q

In which direction does DNA elongation proceed?

A

5’ to 3’

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18
Q

codon =

A

a three base section of DNA/RNA representing one amino acid.

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19
Q

What is the initiation signal?

A

AUG

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20
Q

specific interactions =

A

strong bond which arises from a unique combination of physical forces between macromolecules. Typically involve geometric, steric, ionic and directional bonds

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21
Q

steric interaction =

A

short range quantum repulsion

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22
Q

limits to vDW theory (3)

A

cut-off distance is unknown as it depends on short range repulsive forces
other adhesive forces may be involved eg ionic, hydrogen, hydrophobic
there may be other repulsive forces eg thermal motion of soft surfaces can give rise to thermal fluctuation forces

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23
Q

what is a solvation force

A

a force which oscillates between attractive and repulsive over the size of a water molecule. For a hydrophobic surface this can be smoothly attractive

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24
Q

where is a solvation force attractive or repulsive

A

it is energetically unfavourable to be between layers of water molecules so the force is repulsive away from these regions.

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25
Q

roughly by how far are large molecules separated in a cell

A

a few layers of water molecules

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26
Q

primary structure =

A

the chain of amino acids

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27
Q

secondary structure =

A

how the amino acids are folded. Typically this is in an alpha-helix or beta pleated sheet

28
Q

tertiary structure =

A

how the helix/pleated sheet folds in on itself

29
Q

quaternary structure =

A

how multiple proteins assemble together

30
Q

peptide bond =

A

a bond between the carboxyl group (COO) of one molecule and the amino group (NH) of another

31
Q

three types of side chain which determine protein structure

A

non-polar side chains - these don’t want to be in touch with water so fall in on themselves
polar side chains - want to be in touch with water
electrically charged side chains - have an electric charge in water

32
Q

what interactions determine secondary structure

A

H bonds
for alpha helix, the N-H hydrogen bonds to a backbone C=O
for beta sheet, the beta strands are connected laterally by hydrogen bonds

33
Q

name two unusual interactions that hold tertiary structure together

A

disulphide bond
salt bridge

34
Q

what is a disulphide bond?

A

a covalent bond between the sulphur atoms in two thiol groups.

35
Q

How does a disulphide bond stabalise a protein (3)?

A
  1. Holds two parts of a protein together
  2. The disulfide bond may form the nucleus of a hydrophobic core of the folded protein, i.e., local hydrophobic residues may condense around the disulfide bond and onto each other through hydrophobic interactions.
  3. Related to 1 and 2, the disulfide bond links two segments of the protein chain, increases the effective local concentration of protein residues, and lowers the effective local concentration of water molecules. Since water molecules attack amide-amide hydrogen bonds and break up secondary structure, a disulfide bond stabilizes secondary structure in its vicinity. For example, researchers have identified several pairs of peptides that are unstructured in isolation, but adopt stable secondary and tertiary structure upon formation of a disulfide bond between them.
36
Q

What is a salt bridge?

A

A combindation of hydrogen bonding and electrostatic interactions. They form between electrically charged amino acids eg a COO- and NH3+

37
Q

Afinsen’s dogma =

A

the native structure of a protein is determined only by the amino acid sequence

38
Q

3 consequences of Afinsen’s dogma

A
  1. Uniqueness - each sequence only has one structure
  2. stability - small environmnetal changes won’t change the configuration
  3. kinetic accessability - freen energy path must be fairly smooth ie no random deep dips that a protein could get stuck in
39
Q

levinthal’s paradox =

A

there is an astronomically large set of possible protein configurations yet proteins fold on a milisecond scale

40
Q

name the five main contributors to the total free energy

A
  1. conformational entropy due to loss of degrees of freedom
  2. intramolecular hudrogen bonds and hydrogen bonds between protein and water
  3. van der waals bonds and other hydrophobic bonds
  4. coulomb energy of electrostatic bonds ie salt bridges
  5. valence bond energy and energy from disulphide bridges
41
Q

what holds an alpha helix together?

A

hydrogen bond between backbone N-H and C=O

42
Q

what holds a beta sheet together?

A

backbone hydrogen bonds between strands

43
Q

RNA world hypothesis =

A
  1. Originally there was some pre-RNA biopolymer that could self-replicate.
  2. This was replaced by RNA
  3. This was replaced by RNA and protein systems which required the existence of ribosomes (which are formed of RNA)
  4. New enzymes evolved which can replicate DNA and make RNA copies of it
44
Q

Evidence of RNA world hypothesis (4)

A
  1. RNA can store, replicate and transmit genetic information, just like DNA.
  2. Some viruses use RNA instead of DNA
  3. Ribozymes are catalysts made from RNA
  4. There is evidence for basing building blocks having come from meteorites ie these molecules must be widespread
45
Q

Issues with RNA world hypothesis

A
  1. cytosine only has relatively short lifetime - not long enough for accumulation
  2. RNA is arguably too complex to have arisen prebiotically
  3. catalytit repetoire is too small
  4. need large RNA molecules to perform catalysis
46
Q

How are phylogenetic trees calibrated and why is calibrdation required?

A

Using the fossil record

The numer of divergences in the DNA between two cells is proportional to the time since they diverged, however, the constant of proportionality is different for different proteins.

47
Q

In which groups do amino acids tend to be substituted?

A
  1. Hydrophilic, acidic
  2. Hydrophilic, basic
  3. Polar, uncharged
  4. Hydrophobic
48
Q

Name 4 ways in which genes can be altered

A
  1. Intragenic mutation
  2. Gene duplication
  3. DNA segment shuffling
  4. Horizontal transfer
49
Q

Intragenic mutation =

A

where a mutation occurs within a length of DNA

50
Q

Gene duplication =

A

where a mistake is made during cell division where not all genes are duplicated. The cell does not divide and so contains extra genes which can mutate, and if the mutation is not helpful, the cell can carry on as normal as it still has a good copy of the DNA.

51
Q

DNA segment shuffling

A

where two genes switch some DNA

52
Q

horizontal transfer =

A

where DNA is transferred between two organisms

53
Q

Homology =

A

simliarity due to shared ancestry between a parit of structures of genes

54
Q

Two types of homology

A
  1. Orthology - likely to have same function. Dervie from last common anestor
  2. Parology - likely to have different function. Derive from gene duplication in same gene
55
Q

which level of structure is most conserved?

A

Tertiary

56
Q

Why do we want to understand protein folding?

A
  1. Cheaper to be able to predict structure than use conventional crystallography etc
  2. Helps understand dieses caused by misfolded proteins eg Parkinsons, Alzheimers, mad cow disease
  3. Helps to engineer proteins that could carry out novel functions
57
Q

transition state ensemble =

A

the set of conformations of highest free energy along the path of lowest free energy between the native folded and unfolded macrostates. The TSE limits the rate of folding.

58
Q

How do small proteins fold?

A

In a 2 step process with a low energy barrier. This means they fold quickly.

59
Q

Name 3 ways of probing folding of small proteins

A
  1. Using NMR allows you to see when a region of the protein becomes shielded from the solvant.
  2. Using simulations of the molecular dynamics
  3. By engineering them - mutate a single protein then measure its equilibrium state and kinetics
60
Q

Why is it easier to find the transition state during unfolding of small proteins?

A
  1. The transition state is formed early in the unfolding process so is within the timescale of molecular dynamics simulation
  2. The initial state is the native state which is well defined
61
Q

Number of qays to go from i-1 to i coiled states in binomial model

A

nCi = n!/(i!(n-1)!)

62
Q

Number of qays to go from i-1 to i coiled states in zipper model

A

n-i+1

63
Q

Persistance length of DNA?

A

150bp

64
Q

Error rate of replication

A

1/10^9

65
Q

Three factors that effect replication error rate?

A
  1. Intrinsic error rate ~1/10^7
  2. Proofreading by DNA polymerase
  3. Post replication mismatch repair mechanisms - compare DNA to original
66
Q

Find the probability distribution of a freely jointed chain model

A
67
Q

Derive the mean squared length of a worm like chain model

A

C7 (5 decks)

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