Biology Reference
In-Depth Information
factors that bind regulatory DNA near a gene. The binding
of one or more transcription factors to such regulatory DNA
can activate or repress the transcription of a gene through
interactions with the RNA polymerase that is responsible
for transcribing the gene.
Regulation is often mediated by complex regulatory
circuits. Such circuits consist of multiple molecules that
mutually influence each other's activity. Transcriptional
regulation is no exception. Transcription factors form
regulatory circuits that can comprise dozens of proteins.
These proteins regulate the transcription of the genes
encoding them, and of many other genes downstream of the
circuit genes
[34
These are just two examples where regulatory proteins
and the regulatory circuits they form are critically involved
in the formation of an organism and its parts, as well as in
the formation of a structure that was an innovation when it
first became fully formed. Other prominent examples
include the role of Hox genes in the formation of axial
structures such as limbs in vertebrates, or the role of MADS
box genes in the formation and diversification of flowers
[7, 41
43]
.
e
MACROMOLECULES AND THEIR
INNOVATIONS
Individual proteins and RNA macromolecules are not
usually considered the subject of systems biology, but they
should be. They are systems whose parts are amino acid or
nucleotide monomers. These parts are strung together to
form a whole macromolecule that folds intricately in
three-dimensional space. Such macromolecules are
responsible for all enzyme-catalyzed reactions that take
place in a cell. They serve numerous other functions in
addition, including transport, structural support, and
communication, and they are behind numerous if not all
new molecular functions that originated in life's history.
Some of these functions involve very little change in
a macromolecule's genotype. (This genotype is the DNA
string that encodes the molecule, but for many purposes,
a protein's amino acid sequence or an RNA molecule's
nucleotide sequence can be viewed as the genotype.) An
example of a new function requiring little change involves
the enzyme l-ribulose-5-phosphate 4-epimerase from the
bacterium Escherichia coli, which is necessary for E. coli
to grow on the sugar arabinose as a carbon and energy
source. A single amino acid change from histidine to
asparagine at position 97 of this enzyme suffices to create
a new enzymatic function, an aldolase that joins one
molecule of dihydroxyacetone phosphate and one of gly-
coaldehyde phosphate
[49]
. New functions in other
molecules require greater amounts of amino acid change.
Take as an example antifreeze proteins. These proteins
occur in numerous organisms that have to survive cold
conditions, such as Arctic and Antarctic fish, as well as
overwintering insects and plants. Antifreeze proteins lower
the freezing point of an organism's body fluids. They
originated multiple times independently, in different
organisms, and sometimes rapidly, through multiple amino
acid changes in various ancestor proteins
[50
39]
. In doing so, the circuit's proteins
produce a gene expression pattern in which specific genes
are activated or repressed, a state that can vary in space and
time. A gene expression pattern is a transcriptional regu-
lation circuit's phenotype. Such phenotypes play central
roles in physiology and in embryonic development, the
process that creates a viable adult organism from a fertil-
ized egg
[34,35,40]
.
Regulatory circuits in general, and transcriptional
regulation circuits in particular, are involved in the evolu-
tion of many new traits. One example involves the evolu-
tion of eyespots on the back of butterfly wings
[41
e
43]
.
e
These traits may help butterflies deter predators
[41
43]
.
Eyespots start to form during development in regions that
are called eyespot foci. These foci express the protein
Distal-less, which is causally involved in eyespot forma-
tion. The number of eyespots that form on a wing corre-
sponds to the number of regions that express Distal-less
during early wing development. What is more, grafts of
Distal-less expressing cells to developing wing tissue can
be sufficient for eyespot formation in the graft's recipient
[44]
. Distal-less is a transcription factor, a member of
a complex regulatory circuit with other functions in the
development of wings and legs
[41
e
43]
.
Another example involves the evolution of dissected
leaves in plants
[45, 46]
. The ancestral leaves of flowering
plants were most likely simple leaves, which have an
undivided leaf blade
[47]
. Dissected leaves evolved from
such simple leaves. In a dissected leaf, the leaf blade is
subdivided into multiple smaller leaflets. Leaf dissection is
a trait that may facilitate heat dissipation in hot terrestrial
environments and help increase CO
2
uptake in water
[45,
46]
. Dissected leaves may have originated multiple times in
the evolution of flowering plants
[47]
. During the devel-
opment of dissected leaves, transcription factors of the
KNOX (KNOTTED1-like homeobox) family play a crucial
role. They are expressed in leaf primordials, which form
close to the growing tip of a plant's shoot. Increasing the
expression of KNOX genes during leaf formation can
increase the number of leaflets that are forming; conversely,
reducing their expression can reduce this number of leaflets
[48]
. KNOX genes are part of a regulatory circuit
[48]
.
e
52]
. These
are just two examples of myriad evolutionary innovations
that occurred in biological macromolecules.
All these three kinds of change
e
in metabolism, in
regulatory circuits, and in macromolecules
e
may be
involved in any one innovation, and in ways that are diffi-
cult to disentangle. It is nonetheless useful to study these
e
