the "wild-type" gene, and heterozygous at only a
few loci (about 0.1 %) for mutated alleles that, as
a rule, would be lethal in the homozygous state.
Orily with the introduction in 1966 of enzyme
electrophoresis and the subsequent development
of other methods for analysing informationcarrying macromolecules did population genetics
gain direct access to the genome. A complete
assessment of the genetic differences between
individuals requires the comparison of gene
sequences. However, the methods of DNA and
protein sequencing require too much effort for
comparative investigations of many individuals.
Therefore, popUlation genetics mainly makes use
of the methods of protein electrophoresis and of
DNA analysis by restriction endonuclease digestion. The relatively small amount of data
obtained by the comparative sequencing of several individuals provides useful additional information. In 1966, the first enzyme electrophoretic
investigations of Drosophila pseudoobscura, by
Lewontin and Hubby, and of man, by Harris,
revealed that the amount of genetic variability
was so great that it was described as an "electrophoretic revolution". Using this and other
methods, it has since been demonstrated that a
marked molecular polymorphism exists in almost
all natural populations [17,21, 293,294]. The
characteristic allele frequency for each population remains constant over many generations, as
has been shown, for example, in Drosophila
melanogaster [61].
There are two groups of opposing theories on
the origin of protein polymorphism: The "selectionistic" theories see polymorphism as the outcome of particular forms of selection (balancing
selection) [17], whereas the "neutral" theories
assume that a large proportion of the mutations
and the resulting amino acid substitutions are
selectively neutral, and only by chance (drift) do
they spread through the popUlation and become
fixed. Although the controversy between "neutralism" and "selectionism" is by no means settled,
the results of DNA-sequence analysis today leave
no doubt that many molecular variants behave
like neutral characters during evolution
[210, 212].
4.3.1 Dermitions and Concepts
Prakash, Lewontin and Hubby introduced in 1969
the term "allozyme" for allelic sequence variants
of enzymes; the IUB nomenclature commission
used the name "allelozyme"; linguistically "alle4.3.1 Definitions and Concepts
131
loenzyme" is to be preferred, or in general "aileloproteins". Allelic protein variants usually differ
in only one or a few amino acids. Particularly
large differences of seven amino acids are found
between the allelic variants A and B of the
haemoglobin-~ chain of sheep and the types 1
and 3 alkaline phosphatases from human placenta
[169]. With proteins possessing internal periodicities, allelic length variants are also possible.
Strictly speaking, the terms alleloenzyme or alleloproteins should only be applied when evidence
for allelic inheritance has been obtained from
crossing experiments; however this condition is
rarely fulfilled. It should also be remembered that
the formation of certain post-translational modifications of proteins can, in some cases, be inherited as Mendelian characters (p. 79).
A protein locus is termed polymorphic when
the proportion (frequency) of the most frequent
allele is lower than a certain limit, which is usually given as 0.99 and sometimes as 0.95. For the
quantitative description of protein polymorphism, the proportion P of polymorphic loci at all
the examined loci is often given; however, P is
greatly dependent upon the defined limit and the
genetic constitution of the individual under investigation. Less influenced by this is the heterozygosity of a single locus h:
(4.2)
where Xl is the frequency of the allele i [115, 294].
Averaging h for all the investigated loci gives the
mean heterozygosity, H. In an ideal bisexual
population with random pairing, h corresponds to
the proportion of animals that are heterozygous
at a given locus, and H to the average proportion
of heterozygous loci. In reality, the observed proportion of heterozygotes (Hobs) may deviate
markedly from the expected value (Hexp). Hobs is
heavily dependent upon mating behaviour; incest
and self-fertilization lead to a reduction in Hobs'
In haploid species, hobs is zero by definition.
Thus, only Hexp is suitable for the comparative
assessment of protein polymorphism in different
species, although this is not always accepted in
the literature [148]. To define a protein polymorphism, the actual number of alleles ne may be
given:
(4.3)
The H values determined with enzyme electrophoresis differ greatly even between closely
related species or different populations of a species (Table 4.8). H is seldom greater than 0.3; the
few loci (about 0.1 %) for mutated alleles that, as
a rule, would be lethal in the homozygous state.
Orily with the introduction in 1966 of enzyme
electrophoresis and the subsequent development
of other methods for analysing informationcarrying macromolecules did population genetics
gain direct access to the genome. A complete
assessment of the genetic differences between
individuals requires the comparison of gene
sequences. However, the methods of DNA and
protein sequencing require too much effort for
comparative investigations of many individuals.
Therefore, popUlation genetics mainly makes use
of the methods of protein electrophoresis and of
DNA analysis by restriction endonuclease digestion. The relatively small amount of data
obtained by the comparative sequencing of several individuals provides useful additional information. In 1966, the first enzyme electrophoretic
investigations of Drosophila pseudoobscura, by
Lewontin and Hubby, and of man, by Harris,
revealed that the amount of genetic variability
was so great that it was described as an "electrophoretic revolution". Using this and other
methods, it has since been demonstrated that a
marked molecular polymorphism exists in almost
all natural populations [17,21, 293,294]. The
characteristic allele frequency for each population remains constant over many generations, as
has been shown, for example, in Drosophila
melanogaster [61].
There are two groups of opposing theories on
the origin of protein polymorphism: The "selectionistic" theories see polymorphism as the outcome of particular forms of selection (balancing
selection) [17], whereas the "neutral" theories
assume that a large proportion of the mutations
and the resulting amino acid substitutions are
selectively neutral, and only by chance (drift) do
they spread through the popUlation and become
fixed. Although the controversy between "neutralism" and "selectionism" is by no means settled,
the results of DNA-sequence analysis today leave
no doubt that many molecular variants behave
like neutral characters during evolution
[210, 212].
4.3.1 Dermitions and Concepts
Prakash, Lewontin and Hubby introduced in 1969
the term "allozyme" for allelic sequence variants
of enzymes; the IUB nomenclature commission
used the name "allelozyme"; linguistically "alle4.3.1 Definitions and Concepts
131
loenzyme" is to be preferred, or in general "aileloproteins". Allelic protein variants usually differ
in only one or a few amino acids. Particularly
large differences of seven amino acids are found
between the allelic variants A and B of the
haemoglobin-~ chain of sheep and the types 1
and 3 alkaline phosphatases from human placenta
[169]. With proteins possessing internal periodicities, allelic length variants are also possible.
Strictly speaking, the terms alleloenzyme or alleloproteins should only be applied when evidence
for allelic inheritance has been obtained from
crossing experiments; however this condition is
rarely fulfilled. It should also be remembered that
the formation of certain post-translational modifications of proteins can, in some cases, be inherited as Mendelian characters (p. 79).
A protein locus is termed polymorphic when
the proportion (frequency) of the most frequent
allele is lower than a certain limit, which is usually given as 0.99 and sometimes as 0.95. For the
quantitative description of protein polymorphism, the proportion P of polymorphic loci at all
the examined loci is often given; however, P is
greatly dependent upon the defined limit and the
genetic constitution of the individual under investigation. Less influenced by this is the heterozygosity of a single locus h:
(4.2)
where Xl is the frequency of the allele i [115, 294].
Averaging h for all the investigated loci gives the
mean heterozygosity, H. In an ideal bisexual
population with random pairing, h corresponds to
the proportion of animals that are heterozygous
at a given locus, and H to the average proportion
of heterozygous loci. In reality, the observed proportion of heterozygotes (Hobs) may deviate
markedly from the expected value (Hexp). Hobs is
heavily dependent upon mating behaviour; incest
and self-fertilization lead to a reduction in Hobs'
In haploid species, hobs is zero by definition.
Thus, only Hexp is suitable for the comparative
assessment of protein polymorphism in different
species, although this is not always accepted in
the literature [148]. To define a protein polymorphism, the actual number of alleles ne may be
given:
(4.3)
The H values determined with enzyme electrophoresis differ greatly even between closely
related species or different populations of a species (Table 4.8). H is seldom greater than 0.3; the