Learning Goal
• Understand the evolution of complexity
Expected Learning Outcomes
1) Visualize fitness as a function of gene function for
one and two genes with and without pleiotropy
2) Construct and explain a plausible model for the
evolution of increased complexity
3) Describe and discuss the role of gene duplication
and pleiotropy in the evolution of complexity
4) Infer the history of gene duplication and shifts in
gene function using phylogenetic inference
History of Life
Last universal
common ancestor
was a derived,
complex organism
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
First common
ancestor was
a very simple
organism
Complex
Unicellular
Life
Complex
Unicellular
Life
Complex
Multicellular
Life
Complexity
Complexity evolves by the piece-meal
addition and modification of existing parts
and the sorting of variation by natural
selection over long periods of time.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Origin of Life
Hypercycles
The First Gene?
self-replicating
ribozymes
pleiotropy
consolidation
epistasis
Gene
Proofreading
Metabolism
Synthesis
The First Gene
pleiotropy
functions
gene
Proofreading
Metabolism
Synthesis
Pleiotropy
pleiotropy
functions
gene
Replication
Proofreading
Metabolism
Synthesis
How many functions are possible?
What is the limit to the number of
different functions that can be
encoded by a gene?
pleiotropy
Graph
Number of genes
Draw a frequency distribution showing
what you might expect if you examined
each gene and recorded the number of
different functions each gene performed
(i.e. pleiotropy)
Pleiotropy
(Number of different functions)
Choose Your Graph
A)
B)
C)
E) None of these are my graph
D)
Observed Pleiotropy
Only 1 function
Yeast: a highly
derived eukaryote
Seven different functions
From Wagner and Zhang
Nature Genetics Reviews
A More Complex Critter
From Wagner and Zhang
Nature Genetics Reviews
How does pleiotropy influence the ability of the gene
product to perform a specific function?
Efficiency of a
particular function
Graph It
Number of different functions
A
B
C
D
E) My graph not shown
Evolutionary Model
pleiotropy
gene
The Fitness Model
Function
1
2
Draw a graph of function (xaxis) versus fitness (y-axis)
that represents a model for
antagonistic pleiotropy
W
Function
What does your graph look like?
A
Function
1
2
Partial subfunctionalization
Redundancy
Function
B
Full sub-
Function
functionalization
D
C
Function
Function
E) My graph is not shown
1
2


Functio
n
Given the model, what is the expected function in
the population?
A) 
B) 
C) The function where the two lines cross
D) The average of  and .

1

2
X
Function
1
2


Functio
n
On a piece of paper, draw this graph and use it as a
model to show the fitness cost of pleiotropy relative to a
model in which there is not antagonistic pleiotropy
A
1
2
B
C
D


Functio
n
Choose the value that best represents the fitness cost
of antagonistic pleiotropy relative to a model without
pleiotropy.
a
1
2
Fitness cost
of pleiotropy
b


Function
Subfunctionalization
Pleiotropy
Ancestral Condition
Optimum
a
b
Fitness cost of pleiotropy
Function
Gene Duplication
pleiotropy
gene
redundant pleiotropy
gene
gene
Duplication
Subfunctionalization
Pleiotropy
Reduced pleiotropy
Mutation
Selection
Redundancy
a
b
Function
Partial subfunctionalization
Blue
New expected fitness
Red


Function


New
expected
fitness
ABCDE
Function
Choose the expected trait
value (function) for the
red gene after the blue
gene undergoes
subfunctionalization
A) A
B) B
C) C
D) D
E) E
Subfunctionalization
Pleiotropy
Reduced pleiotropy
Redundancy
a
b
Function
No pleiotropy
Mutation
Mutation
Selection
Selection
Partial subfunctionalization
Full subfunctionalization
Draw the Fitness Model for
the Derived Condition
Pleiotropy
a
b
No pleiotropy
Full subfunctionalization
?
Gene
Function
Ancestral
Derived
Conceptual Model
Pleiotropy
No pleiotropy
Full subfunctionalization
Single
peak
a
b
a
Gene Function
Gene
Function
b
Gene
Function
Conceptual Model
Pleiotropy
No pleiotropy
Full subfunctionalization
a
b
Two-fold
increase in
complexity
One axis to two
Gene Function
a
Gene
Function
b
Gene
Function
Neofunctionalization
New function
Redundancy
Mutation
Mutation
Selection
Selection
Partial subfunctionalization
Time
Neofunctionalization
What Does This Fitness
Model Look Like?
New function
Gene
Function
Gene
Function
Visualization
Multiple
Peaks
New function
Gene
Function
Gene
Function
How Would You Visualize the Model
with a Third Independent Variable?
(i.e 3 genes)
Visualization With Three Genes
Gene 3
Gene 1
Gene 2
Fitness
High
Low
Thinking About Duplication
and Functional Divergence in
the Context of Phylogeny
Genes
Gene
expression
One gene
Two functions
Two genes
Each gene has
two functions
Three genes
Each gene has
one function
Gene
Functions
Note on the tree where gene duplication, subfunctionalization and
neofunctionalization happen using parsimony
D = Duplication
S = Subfunction
N = Neofunction
Functions
Gene
Note on the tree where gene duplication, subfunctionalization
(subfunction) and neofunctionalization (neofunction) happen using
parsimony
1
2
3
A) 1 = duplication,
2 = subfunction,
3 = neofunction
B) 1 = neofunction,
2 = subfunction
3 = duplication
C) 1 = subfunction,
2 = neofunction,
3 = duplication
D) 1 = duplication,
2 = neofunction
3 = subfunction
Note on the tree where gene duplication, subfunctionalization and
neofunctionalization happen using parsimony
N
D = Duplication
S = Subfunction
N = Neofunction
S
D
Functions
Gene
Infer the history of gene duplication, loss and functional modification
Note the ancestral states for each internal node
D = Duplication
S = Subfunction
N = Neofunction
L = Gene loss
Functions
Nodes
Gene
Regulatory Genes
History of Gene Duplication