文档介绍：Pathways Subgroup
Monday 15 May 2000
What is a pathway?
An ordered sequence of proteins and substrates
An evolutionary product
A system
work/graph
A “get-together”
Genes and Pathways
Evolving pathways
Pathways are the product of two parallel “evolutions”
The evolution of proteins and protein function (particularly enzymatic)
The evolution of protein (and substrate) networks
One evolution drives the other… and vice-versa
Theories of pathway evolution I
Horowitz, 1945: Retrograde evolution
Sequential “disappearance” of key intermediary metabolites induces the recruitment of similar available substrates via new enzymes.
Retrograde evolution
S1'
S1''
E1
E3
P1
S1
S1
P1
E1
[S1]
E2
S1'
P1
S1
E1
E2
[S1']
Problems
Each intermediate should be readily available
Many intermediates are labile
There are barriers to metabolite transport
The selective advantage of a pathway may only be apparent when the whole pathway is present
Theories of pathway evolution II
Jensen, 1976: Substrate ambiguity
Enzyme recruitment from a pool of ancestral enzymes with basic functions and substrate ambiguity. Ordered regulated pathways evolved from these ancestral enzymes by gene duplication, followed by increased specialisation.
Substrate Ambiguity