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The Origin of Gene Subfunctions and Genotypic Complexity by Modular
Restructuring
Allan Force, Bill Cresko, F Bryan Pickett, Chris Amemiya, and Mike Lynch
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Evolutionary Time
Subdivision and specialization - a trend in evolution
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Is the Increasing Phenotypic Specialization Reflected in
Underlying Genetic Circuitry?
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What is the default contribution to specialization of body regions at the
genotypic level produced by mutation pressure and genetic drift?
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Modular Restructuring
Evolution of differential connectivity of the genotypic-phenotypic map via subfunction formation and resolutionin developmental genetic networks by nearly neutral processes
.
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Subfunction Formation
Modular Restructuring
Evolution of differential connectivity of the genotypic-phenotypic map via subfunction formation and resolutionin developmental genetic networks by nearly neutral processes
.
.The processes which lead to origin of new gene subfunctionseither by co-option or fission mechanisms
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Subfunction Formation
Subfunction Resolution
Modular Restructuring
Evolution of differential connectivity of the genotypic-phenotypic map via subfunction formation and resolutionin developmental genetic networks by nearly neutral processes
The processes which lead to origin of new gene subfunctionseither by co-option or fission mechanisms
The processes which lead to the partitioning of existingsubfunctions between gene duplicates by DDC mechanisms
.
.
.
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Subfunction 1
Subfunction 2
Multifunctional gene
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Given that many genes are multifunctional, how do new subfunctions evolve?
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Subfunction Co-option
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Subfunction Fission
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TFA
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TFA
AA
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TFA and TFB
TFA
TFB TFA
AA
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TFA and TFB
TFA and TFC
TFA
A
TFB TFC
A
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TFA and TFB
TFA and TFC
TFA
A
TFB
B
TFC
B A
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TFA and TFB
TFA and TFC
TFA
A
TFB
B
TFC
CB CA
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TFA
BC
TFB TFC
B C
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TFB TFC
B C
B
C
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Fission Phase 1: Accretion, Degeneration, and Replacement
Abc
ABc AbC
aBC
ABC
Tim
e?
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abc
aBc Abc abC
ABc aBC AbC
ABC
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State W(Abc)
State X(AbC) or (ABc)
State Y(ABC)
State Z(aBC)
PXW= (1/2a + 4Ne)-1 PYX= (1/a + 4Ne)
-1 PZY= (1/d + 4Ne)-1
PZY= (1/2a + 4Ne)-1PXY= (1/2d + 4Ne)
-1PWX= (1/d + 4Ne)-1
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Effective Population Size (Ne)
101 102 103 104 105 106
Mean T
ime t
o S
ubfu
nction F
issio
n (
genera
tions)
104
105
106
107
108
a = 10-4
a = 10-6
a = 10-5
Time for subfunction fission phase 1 when the addition and deletion rates are equal
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When the time to fission for phase 1 is very long in large effective population sizes does this mean the precursor allele
(ABC allele) is unavailable?
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0
0.25
0.5
0.75
1
0 5 10 15 20
Abc
ABc+AbC
aBC
ABC
Equ
ilib
rium
Fre
quen
cies
Addition Deletion Rate ratio
Infinite population size equilibrium frequencies for the 3 site fission model
a/ d )
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Effective Population Size
Equ
ilib
rium
Fre
quen
cy
101 103 105 107
0.1
0.15
0.2
0.25
0.3
The effect of population size on the equilibrium frequencies under the 3 site fission model
ABC
aBC
Abc
ABc or AbC
d= a
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What about multiple TF binding Sites?
AABBCC
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Sim3 10-4
Sim3 10-5
Sim6 10-4
Sim6 10-5
104
106
108
Gen
erat
ions
101 103 105
1010
Effects of additional TF binding sites on the time to fission phase 1 under the 6 site model
Effective Population Size
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1) Increasing the number of TF binding sites in the 6-site model does not significantly change the behavior relative to the 3-site model, but does reduce the time for phase 1
2) Allowing for different rates of mutation of the A site relative to the B and C sites does not significantly change the behavior of 3 site model for reasonable mutation rates
More complex models have similar behavior to that of the basic 3-site model
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Phase II Enhancer Subfunctionalization
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0.001
0.1
1.0
101 103 105
Ratio1=.25
Ratio2=.75
Ratio1 est 1
Ratio1 est 2
Ratio2 est 1Ratio2 est 2
Pr(
Enh
a nce
r S
ubf u
n cti
ona l
iza t
i on )
Effective Population Size
The probability of enhancer subfunctionalization
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Modular Restructuring
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Subfunction fission leads to the emergence of new subfunctions from the splitting of old subfunctions and may proceed under the guidance of mutation pressure in small populations (N< .1).
More generally, small effective population size and mutation may be sufficient to drive the evolution of the complexity of genes, networks, and developmental pathways passively by modular restructuring.
Changes in the underlying genetic architecture may not be initially observed at the phenotypic level. However, the long-term cumulative effects of modular restructuring may lead to abrupt and rapid changes at the phenotypic level when organisms find themselves exposed to novel environments.
Summary:
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Allan Force Tom MiyakeTom PowersWendy LippmanAlicia Hill -ForceAndrew StuartDebTinnemoreJosh DankeMichael SchoenbornGarnet NavarroAyumi AokiMary West
Chris Amemiya
AMEMIYA LABORATORY
Funding sources: NSF, DOE, NHGRI, NCRR