Biology Reference
In-Depth Information
Chapter 15
Phenotypes and Design Principles
in System Design Space
Michael A. Savageau
Biomedical Engineering Department and Microbiology Graduate Group, University of California, One Shields Avenue, Davis, CA 95616 USA
Chapter Outline
Background
288
Design Principles
298
Systems
288
Alternative Growth Modes of Phage Lambda
298
Wholeness and Open Systems
288
Developmental Decisions
299
Modules
290
Kinetic Model
299
Modules as Elements of Random Change
290
Estimation of Parameter Values
300
Modules as Designed Products of Selection
290
Recast Equations
300
Interface
291
Number of Qualitatively Distinct Phenotypes in Design
Space
Interface and Function
291
301
Interface and Context
292
Example of a Valid Phenotype (Case 11)
302
Design
292
Dominance Conditions
302
Phenotypes
293
Boundaries in System Design Space
302
Generic Concept of Phenotype
294
Example of an Invalid Phenotype (Case 6)
303
Phenotypes from the Analytical Solution
294
Dominance Conditions
303
Phenotypes from the Differential Equation
295
Evaluation of Local Performance
303
Phenotypes in System Design Space
295
Quantitative Criteria
303
Enumeration of Qualitatively Distinct Phenotypes
296
Analysis of Local Performance
303
Robustness
296
Evaluation of Global Performance
305
Characterizing Performance
296
Quantitative Criteria
305
Logarithmic Gain
297
Analysis of Global Performance
305
Parameter Sensitivity
297
Biological Design Principles
305
Response Time
297
Avoiding Inappropriate Switching
306
Global Tolerance
297
Maintaining the Temperate Lifestyle
307
Comparison of Phenotypes
297
Conclusions and Future Challenges
307
Criteria for Functional Effectiveness
297
Acknowledgements
308
Local Performance
297
References
308
Global Tolerance
298
Throughout the pre-genomic era there was sustained interest
in the relationship between genotype and phenotype.
However, the announcement of the draft sequence of the
human genome in 2000 revealed the true magnitude of the
challenge. As Sydney Brenner
[1]
has stated, 'The problems
faced by pre- and post-genomic genetics aremuch the same
the organism there are many intervening levels that form
a rich hierarchy of molecular subsystems. Although we now
have a generic concept of 'genotype' provided by the detailed
DNA sequence, and next-generation sequencing is likely to
produce complete manifestations of this concept in the near
future, there is no corresponding generic concept of 'pheno-
type'. We have only some intuitive notions of what is meant
by phenotype at the level of the organism, hair color of cats,
shape and size of flowers, height and weight of livestock, not
to mention disease states in humans. However, without
e
they all involve bridging the chasm between genotype and
phenotype'. The difficulty in relating these two levels of
biological organization and function is hard to over-estimate.
Moreover, between the levels of genotype and phenotype of
