142
4 Molecular Evolution
During its further development, the neutral
theory diverged from the classification of mutations into three groups (negative, neutral and
positive) to take into account all intermediate
stages between essentially neutral mutations and
those that cause distinct phenotypic effects and
are, therefore, subject to selection [210, 212]. The
fixation probability of a mutation depends upon
the selection coefficient s and the population size
Ne. Very weak negative or positive mutations for
which [Nes] < 1, i.e. where less than one individual will be selected per generation, behave like
neutral mutations. Significantly positive mutations have a higher fixation probability and significantly negative mutations a lower fixation probability. Even a mutation with a high selective advantage of 1 % (s = +0.01) has only a 2 % chance of
fixation; in 98 % of cases it will be lost by chance.
A weakly negative mutation which behaves neutrally in a small population will be subject to selection in a large population [210, 212].
Based on the contribution of single amino
acids to the biochemical and biological properties
of protein molecules, Zuckerkandl has proposed
a further theory of protein evolution. He distinguishes between functions of individual amino
acids, e.g. in the active centre of an enzyme, and
general functions connected to solubility, charge
density, isoelectric point and polarity of the protein. Each amino acid has several general functions, and each general function involves several
amino acids. The exchange of anyone amino acid
may change a general function either positively or
negatively, i.e. on balance such changes may be
selectively neutral. As one of the general functions deviates more and more from the optimum
by such gradual changes, the selective pressure
increases. Thus, the protein fluctuates about the
optimal value for any general function [458,459].
New insights into the importance of specific individual amino acids for protein stability support
this concept [2].
4.4.2 Selection Theories of Polymorphism
For the neutral theories, polymorphism is an
obvious concomitant of molecular evolution
(Fig. 4.7). Selectionism, on the other hand,
attempts to explain stable polymorphism, which
does not just represent a short transitional phase
between different adaptive conditions; it does
this by assuming special mechanisms of "balancing" selection. Three of the most frequently
quoted mechanisms are [135, 294, 300]:
1. Over-dominance between two alleles, when
the heterozygotes are superior to both homozygotes.
2. A selection which is dependent upon the allele
frequency or the population density, or which
differs in consecutive generations.
3. Diversifying selection, i.e. adaptation to the
spatial or temporal variability of environmental parameters (niche theory of protein
polymorphism) .
Heterozygotic advantage is not infrequently
observed in crossing experiments, but may be
confused with the effect of a neutral allele
coupled to a directionally or balanced selected
gene (hitch-hiking effect and associated overdominance). Perfect cases of over-dominance are
otherwise quite rare. The classical case is human
sickle-cell haemoglobin, which increases resistance to malaria in the heterozygotic state and, as
a consequence, reaches frequencies of 20 % in
some African populations. The increased resistance to malaria of heterozygotes is also thought
to be responsible for locally increased frequencies
of ~-thalassaemia, a heritable anomaly in which
the ~-globin chain shows reduced synthesis. One
argument brought against over-dominance as the
explanation for all polymorphism is the high protein polymorphism of natural populations of
haploid organisms like E. coli, Neurospora sp.
and certain moss species, in which no heterozygotes are possible [294, 448].
Frequency-dependent selection as a cause of
protein polymorphism has been convincingly
demonstrated, for example, for the amylase of
Drosophila melanogaster larvae. Homozygotes
for the null allele Amynull produce no active
enzyme, and the higher the frequency of normal
Amyl homozygotes, the higher is the chance of
survival of the null mutants on starch-containing
substrates. Amyl animals apparently release glucose andlor amylose into the substratum [156]. It
is not known exactly which selective advantage
protects the Amynull allele from complete elimination. Frequency-dependent, and thus polymorphism-producing, selection could also be
involved in interactions, for example with predators, parasites or competitors, but there are no
really convincing examples of this [460].
Most important amongst the niche theories is
the environmental grain hypothesis, which is
based on the concept of the habitat of each
population as a mosaic of regions with different
properties. In the case of a "coarse-grained species", each individual is specifically adapted to
4 Molecular Evolution
During its further development, the neutral
theory diverged from the classification of mutations into three groups (negative, neutral and
positive) to take into account all intermediate
stages between essentially neutral mutations and
those that cause distinct phenotypic effects and
are, therefore, subject to selection [210, 212]. The
fixation probability of a mutation depends upon
the selection coefficient s and the population size
Ne. Very weak negative or positive mutations for
which [Nes] < 1, i.e. where less than one individual will be selected per generation, behave like
neutral mutations. Significantly positive mutations have a higher fixation probability and significantly negative mutations a lower fixation probability. Even a mutation with a high selective advantage of 1 % (s = +0.01) has only a 2 % chance of
fixation; in 98 % of cases it will be lost by chance.
A weakly negative mutation which behaves neutrally in a small population will be subject to selection in a large population [210, 212].
Based on the contribution of single amino
acids to the biochemical and biological properties
of protein molecules, Zuckerkandl has proposed
a further theory of protein evolution. He distinguishes between functions of individual amino
acids, e.g. in the active centre of an enzyme, and
general functions connected to solubility, charge
density, isoelectric point and polarity of the protein. Each amino acid has several general functions, and each general function involves several
amino acids. The exchange of anyone amino acid
may change a general function either positively or
negatively, i.e. on balance such changes may be
selectively neutral. As one of the general functions deviates more and more from the optimum
by such gradual changes, the selective pressure
increases. Thus, the protein fluctuates about the
optimal value for any general function [458,459].
New insights into the importance of specific individual amino acids for protein stability support
this concept [2].
4.4.2 Selection Theories of Polymorphism
For the neutral theories, polymorphism is an
obvious concomitant of molecular evolution
(Fig. 4.7). Selectionism, on the other hand,
attempts to explain stable polymorphism, which
does not just represent a short transitional phase
between different adaptive conditions; it does
this by assuming special mechanisms of "balancing" selection. Three of the most frequently
quoted mechanisms are [135, 294, 300]:
1. Over-dominance between two alleles, when
the heterozygotes are superior to both homozygotes.
2. A selection which is dependent upon the allele
frequency or the population density, or which
differs in consecutive generations.
3. Diversifying selection, i.e. adaptation to the
spatial or temporal variability of environmental parameters (niche theory of protein
polymorphism) .
Heterozygotic advantage is not infrequently
observed in crossing experiments, but may be
confused with the effect of a neutral allele
coupled to a directionally or balanced selected
gene (hitch-hiking effect and associated overdominance). Perfect cases of over-dominance are
otherwise quite rare. The classical case is human
sickle-cell haemoglobin, which increases resistance to malaria in the heterozygotic state and, as
a consequence, reaches frequencies of 20 % in
some African populations. The increased resistance to malaria of heterozygotes is also thought
to be responsible for locally increased frequencies
of ~-thalassaemia, a heritable anomaly in which
the ~-globin chain shows reduced synthesis. One
argument brought against over-dominance as the
explanation for all polymorphism is the high protein polymorphism of natural populations of
haploid organisms like E. coli, Neurospora sp.
and certain moss species, in which no heterozygotes are possible [294, 448].
Frequency-dependent selection as a cause of
protein polymorphism has been convincingly
demonstrated, for example, for the amylase of
Drosophila melanogaster larvae. Homozygotes
for the null allele Amynull produce no active
enzyme, and the higher the frequency of normal
Amyl homozygotes, the higher is the chance of
survival of the null mutants on starch-containing
substrates. Amyl animals apparently release glucose andlor amylose into the substratum [156]. It
is not known exactly which selective advantage
protects the Amynull allele from complete elimination. Frequency-dependent, and thus polymorphism-producing, selection could also be
involved in interactions, for example with predators, parasites or competitors, but there are no
really convincing examples of this [460].
Most important amongst the niche theories is
the environmental grain hypothesis, which is
based on the concept of the habitat of each
population as a mosaic of regions with different
properties. In the case of a "coarse-grained species", each individual is specifically adapted to