evolution of protein function

Question 1

sequence similarity networks

Answer 1

• use of phylogenetic relationships to interpret function
• summarise relationships between proteins
• blast info creates dot for each protein
  
  • link dots if score greater than threshold
  • dot colour indicates function

Question 2

protein families

Answer 2

• family expansion and subfamily identification possible in large phylogenies
• some residues strongly associated with 1 binding site in a family and not another
  
  • M13 peptidases
• expose different family members to different ligands
  
  • classify subfamilies by ligand interactions and specificity-determining residues

Question 3

M13 peptidases

Answer 3

• 2 binding sites
  
  • S1’ and S2’
  • require different residues
• analyse residue characteristics
  
  • S1’ hydrophobic
  • S2’ polar/charged
• use to classify subfamily

Question 4

specificity profiles

Answer 4

• show specificity at each position of a binding domain
  
  • e.g. PDZ domain
• can study evolution of function
• higher column = increased binding
  
  • small column = little binding
  • no letter = no binding at that position
• single letter indicates only that letter present and binding

Question 5

profile clusters

Answer 5

• cluster based on similarity
• create objective classification system
  
  • not the same as phylogeny
• corresponds well to binding classes
  
  • e.g. PDZ domains - highly conserved specificity profiles

Question 6

ortholog vs paralog

Answer 6

• ortholog = related via speciation
  
  • similar function, especially if an essential function
  • strong selection pressure to retain function
• paralog = related via gene duplication

Question 7

paralogs

Answer 7

• indicate a gene duplication becomin fixed in a populaiton
• indicates selection pressure to retain both paralogs
  
  • assuming a cost to maintain gene in the genome
• cna mutate and adopt novel functions
  
  • multiple copies of essential gene

Question 8

glucose transporter genes

Answer 8

• s. cerevisiae
  
  • artifical selection pressure from humans
  • duplication of glucose transporter genes
• c. albicans
  
  • exploits host glucose
  • many paralogs
  • some transporters similar to humans
    
    • immune evasion

Question 9

fate of paralogs

Answer 9

• maintain original function
  
  • increase dosage
• subfunctionalisation
  
  • more specialised function
  • division of ancestral function
• neofunctionalisation
  
  • evolve a new function

Question 10

tree reconciliation

Answer 10

• labelling internal nodes of trees as duplication or speciation
• need to understand context
  
  • can’t assign by looking at node on its own
• important for developing correct phylogeny

Question 11

tree reconciliation

parsimony

Answer 11

• maximally parsimonious
• finds a solution that minimises the number of duplications and losses by node labelling

Question 12

bootstrap support values

Answer 12

• at each node
• indication of degree of confidence in separation of parts of a tree
• some branches more reliable than others
• investigate weaker branches
  
  • collapse and rearrange to find a better solution with smaller cost

Question 13

cost of a tree

Answer 13

• involves duplication and losses
• genes easily lsot from genomes
  
  • smaller cost
• assuming cost of keeping gene in genome:
  
  • duplication is costly

Question 14

ancestral states

Answer 14

• can label gene tree nodes with names of corresponding ancestral species using reconciled phylogenies
• can infer attributes of extinct ancestors
• infer most likely ancestral protein sequence using maximum likelihood
• synthesise protein e.g. rhodopsin and observe properties