Biology Reference
In-Depth Information
modules that were recognized very early in the study of
metabolism. Beginning in the late 1950s, it was recognized
by Umbarger and Pardee and their colleagues that
biosynthetic pathways involving end-product inhibition
represent a prevalent module
[8,9]
, and they and others
noted that these modules were very analogous to techno-
logical devices based on feedback control. At the level of
genetic encoding, Jacob and Monod
[10]
were quick to
point out the implications of the operon module as
a building block for metabolic and other functions.
The overall architecture of metabolism noted by Davis
[11]
provides numerous examples of the types of modules I
have in mind. There is a large 'fan in' of catabolic pathways
that converge toward the central region of intermediary
metabolism, which is primarily concerned with energy
production and the formation and exchange of small
molecular weight intermediates. The products of interme-
diary metabolism then lead to a large 'fan out' of biosyn-
thetic pathways that synthesize all the building blocks for
the construction of a cell (
Figure 15.2
).
This overall organization greatly facilitated the study of
metabolism and its genetic regulation. The pathways on the
periphery tend to be modular, specialized, minimally con-
nected to the main body of the metabolic network, and
highly regulated. Classic examples of such systems include
the lactose, arabinose and maltose catabolic systems, and
the tryptophan, arginine and histidine biosynthetic systems.
Their boundaries are relatively well defined and their
physiological function is at least qualitatively clear,
conditional mutants are easily selected, experimental
studies can be performed without major perturbation of the
other cellular subsystems, and the extent of regulation is
large and easily detected. The modularity of these systems
greatly facilitated the allocation of experimental effort,
which led to rapid advances in understanding with separate
modules being studied in parallel in separate laboratories
around the world.
These studies also showed that the control of gene
expression for these systems occurs largely at the level of
transcription initiation, and that these modular systems are
under the control of a small number of transcriptional
regulators, mostly a combination of two or three specific
and global regulators. It was found that control of effector
gene expression in functionally similar systems neverthe-
less shows considerable diversity: changes in expression
could be signaled by substrates, intermediates or products;
controlled by activators or repressors; and coupled or
uncoupled from regulator gene expression
[12]
.
Modules as elements of change facilitate the random,
combinatorial exploration of design space that creates the
variation upon which natural selection acts. Modules as
functional subsystems are the provisional fruits of natural
selection that exhibit design principles. Their modularity
facilitates the quantitative analysis and controlled
comparison that lead to a deeper understanding of alter-
native designs.
Interface
The modules of technological systems are designed to have
a common interface, e.g., conducting wires in electrical
systems. Such modules also are more concerned with the
transformation of signals or information than with the
transformation of material. However, modules of biological
systems are designed by natural selection to have fairly
specific interfaces involving physical
chemical recogni-
tion of the molecules involved. Such modules also are often
concerned necessarily with the transformation of material
as well as with signals or information.
e
Interface and Function
The interface through which one biological module inter-
acts with another is typically related intimately to its
function. The term 'function' is used throughout this
chapter, and is used throughout biology in many different
ways. A metal in the reaction center of an enzyme might be
said to have the function of coordinating various ligands in
the protein. An enzyme in a signal transduction cascade
might be said to have a kinase function. An operon in
a metabolic system might be said to have an inducible
catabolic function for supplying carbon in the production of
biomass. When speaking of the function of a system, I mean
this in the broadest terms to include not only such
descriptive or qualitative characteristics, but also the
quantitative aspects of performance such as specificity and
activity of an enzyme, the behavior in time, such as how
fast the system responds and the duty cycle specifying how
often it may be required to respond, as well as more
complex
FIGURE 15.2
Overall organization of metabolism. A converging set
of inducible catabolic pathways leads into intermediary metabolism, and
a diverging set of repressible biosynthetic pathways leads out. See text for
further discussion.
dynamic
behavior
including
homeostasis,
robustness,
tolerance,
oscillations,
synchronization,
