Principles in Biology a consequence of evolution and natural selection Rui Alves University of Lleida ralvescmbudles Climbing down mount improbable Overtime ID: 392777
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Slide1
Design Principles in Biology:
a
consequence
of
evolution
and natural
selection
Rui
Alves
University
of Lleida
ralves@cmb.udl.esSlide2
Climbing
down
mount improbable
Overtime, edged stones would accumulate on the slope.Smooth, round, stonesaccumulate at the bottom.
Design
Principles
:
-
Smooth
,
roundish
rocks
roll
down
the
mountain
.
-
Edged
, flat,
rocks
don’t
.Slide3
Design principles in molecular biology Similarly, if a topology or set of parameters can be shown to create a molecular network that functionally outperforms all other possible alternatives in a given set of conditions, one can talk about a design principle for the system under those conditions.
[
sensu engineering]Slide4
Index of talk How to identify design principles in molecular networks
Design principles in:
Gene expression
Metabolic networksSignal transductionDevelopmentDesign principles, what are they good for?SummarySlide5
First step, define the alternatives
Gene
Regulator
+
Gene
Regulator_
X0 X1 X2 X3
X0 X1 X2 X3Slide6
First step, define the alternatives
X0 X1 X2 X3
X3
t
How strong should the feedback be? Slide7
Then, create models for each alternative
Gene
Regulator
+
Gene
Regulator_Slide8
Then, create models for each alternative
X0 X1 X2 X3
X0 X1 X2 X3Slide9
Characterization
of
network
behavior
Biological functional effectiveness criteria for the network. Alternative designsX1 …
Xj …
X1 …
Xj
…
…
Mathematical models
Enforce mathematical controls before analyzing model behavior
Comparison
of
behavior
between
networksSlide10
Index of talk How to identify design principles in molecular networks
Design principles in:
Gene expressionMetabolic networks
Signal transductionDevelopmentDesign principles, what are they good for?SummarySlide11
The demand theory for gene expressionAre there situations where positive regulation of gene expression outperforms negative regulation of gene expression and vice versa?
Gene
Regulator
+
Gene
Regulator_Slide12
Regulating gene expression has principlesPositive regulator:
More effective when gene product in demand for large fraction of life cycle.
Less noise sensitive if signal is low.
Negative regulator:More effective when gene product in demand for small fraction of life cycle.Less noise sensitive if signal is high.
GeneRegulator+
GeneRegulator
_
Genetics
149:1665; PNAS 103:3999; PNAS 104:7151;Nature 405
: 590Slide13
Glycogen
Trehalose
Regulating gene expression has principlesSlide14
Design principles in developmentSlide15
Design principles in developmentSlide16
Index of talk How to identify design principlesDesign principles in:
Gene expression
Metabolic networks
Signal transductionDevelopmentDesign principles, what are they good for?SummarySlide17
Negative overall feedback is a design principle in metabolic biosynthesis
X0 X1 X2 X3
Negative overall feedback:
More effective in coupling
production to demand.
More robust to fluctuations.
Bioinformatics
16:786;
Biophysical
J. 79:2290Slide18
Index of talk How to identify design principlesDesign principles in:
Gene expression
Metabolic networks
Signal transductionDevelopmentDesign principles, what are they good for?SummarySlide19
Bifunctional sensors can be a design principle in signal transduction
Bifunctional
sensor:
Performs best against cross talk
Independent deactivator:
Better integrator of signals
Mol.
Microbiol
. 48:25; Mol.
Microbiol
. 68: 1196
Signal
Sensor
Sensor
Efector
Efector
Deactivator
Effect Slide20
Index of talk How to identify design principlesDesign principles in:
Gene expression
Metabolic networks
Signal transductionDevelopmentDesign principles, what are they good for?SummarySlide21
Gene
Regulator
_
Design principles in development
Gene
Regulator+High demand
, low signal
Signal
+
High demand
, high signal
Low demand,
high signal
Low demand,
low signal
Signal
_
Genetics 149:1665; PNAS 103:3999; PNAS 104:7151;Nature 405: 590Slide22
Index of talk How to identify design principles
Design principles in:
Gene expression
Metabolic networksSignal transductionDevelopmentDesign principles, what are they good for?SummarySlide23
Biological design principles are good to understand why biology works as it doesBiological design principles may connect molecular determinants to functional effectiveness.
Heat
shock
Expression
of
important
genes
time
Growth
rate
time
BMC
Bioinformatics
7:184Slide24
Underlying assumptionEvolution of molecular networks can be treated as modules.Work in the group of Uri Alon
suggests that
networks evolving to meet simultaneous goals evolve in a modular fashion
Networks evolving to meet a single goal evolve globallyModularity seems like a reasonable first assumptionPNAS 102:13773; PLOS Comp
Biol 4:e1000206;BMC Evol biol 7: 169Slide25
The good news about functionSometimes, you get stuff for free!!!For example:
networks that are responsive to signals, just because they are responsive may have inbuilt buffering of noise.
Functions that are associated with marginally stable proteins are favored because due to the large dimensions of sequence space most randomly selected sequences have a structure that is marginally stable.
PNAS 100:14463; PNAS 103:6435; Proteins 46:105Slide26
How can biological design principles be applied?
Design of molecular circuits with specific behaviors!!
Stable
SystemsUnstable systemsOscilations
Bistable systemsCell 113: 597; PLoS
Comput Biol. 5:e1000319; PNAS 106: 6435Slide27
Index of talk How to identify design principles
Design principles in:
Gene expression
Metabolic networksSignal transductionDevelopmentDesign principles, what are they good for?SummarySlide28
SummaryDesign principles can be found in molecular networks.Such principles can sometimes be connected to selection for function effectiveness.Even in the absence of such a connection, if they are valid they can be used to build biological circuits with specific behaviors.Slide29
AcknowledgmentsMike SavageauAlbert
Sorribas
Armindo
SalvadorOleg Igoshin
Programa Ramon y Cajal MCyTMCyTFCT
NIH