128
4 Molecular Evolution
ferent characters according to the biological function: for cellular enzymes this is, for example, the
maximal flux at the substrate concentrations
occurring in the cells; for regulatory enzymes it is
the high sensitivity to changing conditions; for
digestive enzymes it is the constant turnover rates
by substrate saturation; and for detoxifying enzymes it is the best possible protection of the organism as a result of reduced substrate specificity
[48, 328]. To answer the question of how far cellular enzymes have already been "perfected" during the course of evolution, an efficiency coefficient Ef has been defined, and this reaches the
value of 1 when the flux is limited by only the
diffusion processes of substrate binding and product release. In these terms, there are many enzymes that may be looked upon as perfect catalysts.
However, the catalytic potential of an enzyme in
vivo is so dependent upon its molecular environment, for example, due to the binding to multienzyme complexes or cellular structures or to
metabolic compartmentalization, that kinetic
parameters defined in vitro are of doubtful value
for assessing the degree of perfection reached in
evolution. The interaction of enzyme molecules
with other proteins is made easier by the almost
completely spherical form of the enzymes; this
may also be of importance in the evolution of
enzymes.
The evolutionary adaptation of proteins to
changed conditions involves the effects of positive selection. For this there is usually no requirement for new, "adaptive", genetic changes; molecular adaptation can take account of the variability already present in the population, in that previously neutral variants may acquire a positive
selection value under the new conditions
[210, 212]. The functional characters of protein
are specified by, in particular, their spatial structure. Compared with the large number of possible
amino acid sequences, there is a limited number
of architectural classes. Therefore, far-reaching
changes in amino acid sequence can occur during
protein evolution without there being any change
in spatial structure, which is very conservative.
The most investigated example of this is the globin family, whose spatial structures are very similar despite the existence of up to 84 % sequence
difference (see Fig. 7.4, p. 252); further examples
include the serine proteases, the pepsin-like proteases and the enzyme pair, avian lysozyme/mammalian a-lactalbumin. In some cases, one finds
similar spatial structure without significant
sequence similarity, e.g. comparing globins with
cytochrome bs, or avian with phage lysosomes.
The question remains whether these are homologous proteins, whose sequence similarities have
been lost during evolution, or proteins of similar
spatial structure, resulting from convergent
evolution.
In the course of the evolution of organisms,
proteins with completely novel functions have
continuously appeared. A wide range of new
types of protein were required when the vertebrates appeared approximately 500 million years ago
and a large variety of different life forms with unique organ systems came into being. Research into
molecular homology has made it possible to
describe the origin and evolution of several typical vertebrate proteins. This is true, for example,
for proteins of the eye lens: the exons 2 and 3 of
the a-crystallin gene are related to the very
ancient genes for the heat-shock proteins; ~crystallin and y-crystallin possibly developed
from Ca 2 + -binding proteins; the ~-crystallin is
homologous with arginosuccinate lyase which,
because of its central role in arginine biosynthesis
and purine metabolism, is ubiquitous and the Ecrystallin is simply an altered lactate dehydrogenase (p. 367).
The a-lactalbumin of mammals, the regulatory
chain of the dimeric lactose synthase, is related to
the lysozyme from the chicken egg. During its
evolution from the carbohydrate-hydrolysing
enzyme, the a-lactalbumin has retained its sugarbinding capability but lost the hydrolytic property. The super-family of the serine proteases
includes not only the various protein components
of blood-clotting, fibrinolysis and the complement system but also haptoglobin, which binds
haemoglobin from degraded erythrocytes and
transports it to the liver. Here also, the newly
appearing protein has retained the ability for specific binding to polypeptides at the expense of the
hydrolytic property. Caeruloplasmin, which serves to transport copper in the blood plasma, is
homologous to the blood-clotting components
fibrinogen, factor V and factor VII. The apparently quite old proteinase inhibitor a2M is related
not only to a pregnancy protein but also to the
complement components C3, C4 and C5. There is
a completely unexpected homology over a stretch
of 101 amino acids between the linker protein in
the proteoglycan complex of cartilage and the Tcell receptor; in this case, a component of the
immune system appears to have arisen by modification of a cell-matrix protein [36, 94]. Even
today, enzymes with new substrate or reaction
specificities can arise; an example of this is the
dichlorodiphenyltrichloroethane (DDT) dechlo-
4 Molecular Evolution
ferent characters according to the biological function: for cellular enzymes this is, for example, the
maximal flux at the substrate concentrations
occurring in the cells; for regulatory enzymes it is
the high sensitivity to changing conditions; for
digestive enzymes it is the constant turnover rates
by substrate saturation; and for detoxifying enzymes it is the best possible protection of the organism as a result of reduced substrate specificity
[48, 328]. To answer the question of how far cellular enzymes have already been "perfected" during the course of evolution, an efficiency coefficient Ef has been defined, and this reaches the
value of 1 when the flux is limited by only the
diffusion processes of substrate binding and product release. In these terms, there are many enzymes that may be looked upon as perfect catalysts.
However, the catalytic potential of an enzyme in
vivo is so dependent upon its molecular environment, for example, due to the binding to multienzyme complexes or cellular structures or to
metabolic compartmentalization, that kinetic
parameters defined in vitro are of doubtful value
for assessing the degree of perfection reached in
evolution. The interaction of enzyme molecules
with other proteins is made easier by the almost
completely spherical form of the enzymes; this
may also be of importance in the evolution of
enzymes.
The evolutionary adaptation of proteins to
changed conditions involves the effects of positive selection. For this there is usually no requirement for new, "adaptive", genetic changes; molecular adaptation can take account of the variability already present in the population, in that previously neutral variants may acquire a positive
selection value under the new conditions
[210, 212]. The functional characters of protein
are specified by, in particular, their spatial structure. Compared with the large number of possible
amino acid sequences, there is a limited number
of architectural classes. Therefore, far-reaching
changes in amino acid sequence can occur during
protein evolution without there being any change
in spatial structure, which is very conservative.
The most investigated example of this is the globin family, whose spatial structures are very similar despite the existence of up to 84 % sequence
difference (see Fig. 7.4, p. 252); further examples
include the serine proteases, the pepsin-like proteases and the enzyme pair, avian lysozyme/mammalian a-lactalbumin. In some cases, one finds
similar spatial structure without significant
sequence similarity, e.g. comparing globins with
cytochrome bs, or avian with phage lysosomes.
The question remains whether these are homologous proteins, whose sequence similarities have
been lost during evolution, or proteins of similar
spatial structure, resulting from convergent
evolution.
In the course of the evolution of organisms,
proteins with completely novel functions have
continuously appeared. A wide range of new
types of protein were required when the vertebrates appeared approximately 500 million years ago
and a large variety of different life forms with unique organ systems came into being. Research into
molecular homology has made it possible to
describe the origin and evolution of several typical vertebrate proteins. This is true, for example,
for proteins of the eye lens: the exons 2 and 3 of
the a-crystallin gene are related to the very
ancient genes for the heat-shock proteins; ~crystallin and y-crystallin possibly developed
from Ca 2 + -binding proteins; the ~-crystallin is
homologous with arginosuccinate lyase which,
because of its central role in arginine biosynthesis
and purine metabolism, is ubiquitous and the Ecrystallin is simply an altered lactate dehydrogenase (p. 367).
The a-lactalbumin of mammals, the regulatory
chain of the dimeric lactose synthase, is related to
the lysozyme from the chicken egg. During its
evolution from the carbohydrate-hydrolysing
enzyme, the a-lactalbumin has retained its sugarbinding capability but lost the hydrolytic property. The super-family of the serine proteases
includes not only the various protein components
of blood-clotting, fibrinolysis and the complement system but also haptoglobin, which binds
haemoglobin from degraded erythrocytes and
transports it to the liver. Here also, the newly
appearing protein has retained the ability for specific binding to polypeptides at the expense of the
hydrolytic property. Caeruloplasmin, which serves to transport copper in the blood plasma, is
homologous to the blood-clotting components
fibrinogen, factor V and factor VII. The apparently quite old proteinase inhibitor a2M is related
not only to a pregnancy protein but also to the
complement components C3, C4 and C5. There is
a completely unexpected homology over a stretch
of 101 amino acids between the linker protein in
the proteoglycan complex of cartilage and the Tcell receptor; in this case, a component of the
immune system appears to have arisen by modification of a cell-matrix protein [36, 94]. Even
today, enzymes with new substrate or reaction
specificities can arise; an example of this is the
dichlorodiphenyltrichloroethane (DDT) dechlo-