lecture 14 - bioinformatics: homologous evolution

Question 1

how do we use bioinformatics info? (4)

Answer 1

(1) for determining 3D structures
(2) can’t predict 3D structure from sequence - need additional info, but can predict similar structures
(3) can predict tertiary structure quite well
(4) to analyze evolutionary relationships

Question 2

define homologous

Answer 2

• 2 sequences that are derived from a common ancestor

- commonly >25% sequence identity in aa sequence

Question 3

what do homologous sequences imply?

Answer 3

an evolutionary relationship

Question 4

sequences can be either

Answer 4

homologous or not

Question 5

how do we describe sequence similarity for homologous sequences?

Answer 5

as a % identity

Question 6

define paralogous

Answer 6

homologous within one species

Question 7

define orthologous

Answer 7

homologous within different species

Question 8

mechanism for paralogous genes

Answer 8

• gene encoding a specific enzyme undergoes a mutation

- now have enzyme 1 and enzyme 2 that have evolved to have different, often related, functions

Question 9

example of paralogous proteins

Answer 9

trypsin and chymotrypsin

Question 10

mechanism for orthologous genes

Answer 10

• dna encoding a specific protein in a species undergoes speciation
• now have enzyme w identical or similar functions in two species (e.g. mouse and rat)

Question 11

how do homologues arise? what is the result?

Answer 11

• divergent evolution

- resulting in similar structure and function

Question 12

define convergent evolution

Answer 12

common or similar function but unrelated sequences

Question 13

example question:

calpain-1 and calpain-2 = 65% identity in human genome

calpain-2 in rat, mouse, cow, sheep and humans = 93%-98% = identical

what does this imply?

Answer 13

this implies calpain-1/calpain-2 diverged before those species appeared

Question 14

comparing homologues with similar function and discvoering conserved residues tells us what?

Answer 14

implies those residues are important for function

Question 15

what are 2 possible reasons conserved residues are important for function?

Answer 15

(1) they play a direct role in function (e.g. enzyme catalysis or binding ligand)
(2) they play an indirect role needed to maintain structure of the protein (function depends on structure)

Question 16

can some residues be substituted conservatively? if so which ones?

Answer 16

yes

• Leu –> Ile
• Asp –> Glu-
• Arg –> lys+

Question 17

where are less conserved regions found? why are they found here?

Answer 17

• loops

- link the “important” parts together