[63]. In this way, it has become clear that this phenomenon is extremely important in evolution.
The insertion or deletion of mobile elements are
apparently frequent events with mutation rates of
more than 10- 5 per generation. During the
"hybrid dysgenesis" that occurs in the progeny of
a male Drosophila with transposase-producing P
or I elements and a female lacking elements, the
transposition rate for these elements, and also for
other mobile elements, increases transiently to as
high as 10- 2 [131].
The insertion or deletion of transposable elements usually leads to extensive rearrangements in
the affected DNA region, and this may be one of
the main causes of sexual isolation and, thereby,
the formation of new species [400]. The sequence
equalization between members of a mUlti-gene
family (horizontal evolution) can be prevented by
such insertions; thus, the Alu elements found at
different sites in the mammalian ~-globin gene
cluster have allowed the development and maintenance of adaptive differences between embryonal, foetal and adult globins [39, 365]. The insertion of a transposable element in a transcription
unit or in a region flanking a gene may inhibit
gene expression, or it may stimulate expression
by the introduction of a promoter or a
transcription-enhancing sequence (an enhancer);
the enhancer may make the gene hormonedependent. The introduction of a termination signal, e.g. in an intron, can produce an entirely new
gene [131]. The phenotypic consequences of a
transposition are determined by the nature of the
transposed sequence and by the site of insertion.
Hence, in the Drosophila notch locus, various
mobile elements create completely different eye
mutants [206].
It appears that a large proportion of spontaneous mutations of complex phenotypic characters
involve the insertion of mobile elements into active regions of the genome. For example, in Drosophila, different eye-colour mutations are
caused by the insertion of such elements into the
white locus; in some cases these are reversed by
their deletion [45]. The expression of the Drosophila gene Sgs-4 is reduced 50- to 100-fold by
insertion of the mobile element "hobo" into the
5' controlling region; this gene codes for a glue
protein in the salivary gland of the larvae. The
glue protein sticks the pupal membrane to the
substratum surface [269]. In a "low-activity"
strain of Drosophila melanogaster, transposition
of copia or copia-like elements to particular "hot
spots" brings about a drastic increase in mating
success [317]. In two human patients with the
4.2.5 The Evolution of Multi-Gene Families
123
blood-clotting deficiency haemophilia A, which
involves the absence of factor VIII, an L1 element has been found inserted into exon 14 of the
factor VIII gene on the X chromosome [203]. The
insertion of Alu repeats can result in widespread
rearrangements and thus to dysfunction of the
genes, as seen, for example, in LDL receptors, in
the ~-globin cluster and in the gene for the inhibitor of the complement component C1 [39, 397].
4.2.5 The Evolution of Multi-Gene Families
Multi-gene families show special evolutionary
phenomena such as homogenization of sequences, evolutionary changes in copy number and the
formation of pseudogenes. In particular, a gene
family organized as a coherent gene cluster represents a genetic unit, a "super gene" [21]. The
sequence similarity between the genes of a family
is the result of a particular evolutionary process
known as concerted, coincident or horizontal
evolution. This cannot simply be the result of
selection, because there is undoubtedly no strong
selection pressure if one of many identical genes
mutates. The terms "concerted" and "coincident"
are not appropriate in that the selection-driven,
parallel evolution of all members of a family is
not involved, but rather a process which, on the
one hand, mutually aligns the sequences of all
members and, on the other hand, allows variants
to spread rapidly throughout the whole family
and subsequently become fixed in the population.
Horizontal evolution has been closely investigated in 18S and 28S rDNA, in 5S rDNA, in the
globin, immunoglobulin, histone and heat-shock
genes and in various families of repetitive DNA.
It is still an open question how the sequence consistency of human mtDNA is maintained. Whilst
the mtDNA of different individuals may vary by
almost 0.5 %, in anyone individual only one nucleotide substitution can be detected in a total of
49 kb [280].
Two mechanisms are mainly responsible for the
intrachromosomal recombination and horizontal
evolution in multi-gene families, namely unequal
crossing-over and gene conversion (Fig. 4.4).
Both involve the mismatching of DNA sequences, for which repetitive sequences are usually
responsible [234]. For effective gene conversion,
the homologous sequence must be at least 200 bp
long [249]. In crossing-over, chromatid segments
are exchanged during meiosis, or also during
mitosis if mitotic chromosome pairing takes
The insertion or deletion of mobile elements are
apparently frequent events with mutation rates of
more than 10- 5 per generation. During the
"hybrid dysgenesis" that occurs in the progeny of
a male Drosophila with transposase-producing P
or I elements and a female lacking elements, the
transposition rate for these elements, and also for
other mobile elements, increases transiently to as
high as 10- 2 [131].
The insertion or deletion of transposable elements usually leads to extensive rearrangements in
the affected DNA region, and this may be one of
the main causes of sexual isolation and, thereby,
the formation of new species [400]. The sequence
equalization between members of a mUlti-gene
family (horizontal evolution) can be prevented by
such insertions; thus, the Alu elements found at
different sites in the mammalian ~-globin gene
cluster have allowed the development and maintenance of adaptive differences between embryonal, foetal and adult globins [39, 365]. The insertion of a transposable element in a transcription
unit or in a region flanking a gene may inhibit
gene expression, or it may stimulate expression
by the introduction of a promoter or a
transcription-enhancing sequence (an enhancer);
the enhancer may make the gene hormonedependent. The introduction of a termination signal, e.g. in an intron, can produce an entirely new
gene [131]. The phenotypic consequences of a
transposition are determined by the nature of the
transposed sequence and by the site of insertion.
Hence, in the Drosophila notch locus, various
mobile elements create completely different eye
mutants [206].
It appears that a large proportion of spontaneous mutations of complex phenotypic characters
involve the insertion of mobile elements into active regions of the genome. For example, in Drosophila, different eye-colour mutations are
caused by the insertion of such elements into the
white locus; in some cases these are reversed by
their deletion [45]. The expression of the Drosophila gene Sgs-4 is reduced 50- to 100-fold by
insertion of the mobile element "hobo" into the
5' controlling region; this gene codes for a glue
protein in the salivary gland of the larvae. The
glue protein sticks the pupal membrane to the
substratum surface [269]. In a "low-activity"
strain of Drosophila melanogaster, transposition
of copia or copia-like elements to particular "hot
spots" brings about a drastic increase in mating
success [317]. In two human patients with the
4.2.5 The Evolution of Multi-Gene Families
123
blood-clotting deficiency haemophilia A, which
involves the absence of factor VIII, an L1 element has been found inserted into exon 14 of the
factor VIII gene on the X chromosome [203]. The
insertion of Alu repeats can result in widespread
rearrangements and thus to dysfunction of the
genes, as seen, for example, in LDL receptors, in
the ~-globin cluster and in the gene for the inhibitor of the complement component C1 [39, 397].
4.2.5 The Evolution of Multi-Gene Families
Multi-gene families show special evolutionary
phenomena such as homogenization of sequences, evolutionary changes in copy number and the
formation of pseudogenes. In particular, a gene
family organized as a coherent gene cluster represents a genetic unit, a "super gene" [21]. The
sequence similarity between the genes of a family
is the result of a particular evolutionary process
known as concerted, coincident or horizontal
evolution. This cannot simply be the result of
selection, because there is undoubtedly no strong
selection pressure if one of many identical genes
mutates. The terms "concerted" and "coincident"
are not appropriate in that the selection-driven,
parallel evolution of all members of a family is
not involved, but rather a process which, on the
one hand, mutually aligns the sequences of all
members and, on the other hand, allows variants
to spread rapidly throughout the whole family
and subsequently become fixed in the population.
Horizontal evolution has been closely investigated in 18S and 28S rDNA, in 5S rDNA, in the
globin, immunoglobulin, histone and heat-shock
genes and in various families of repetitive DNA.
It is still an open question how the sequence consistency of human mtDNA is maintained. Whilst
the mtDNA of different individuals may vary by
almost 0.5 %, in anyone individual only one nucleotide substitution can be detected in a total of
49 kb [280].
Two mechanisms are mainly responsible for the
intrachromosomal recombination and horizontal
evolution in multi-gene families, namely unequal
crossing-over and gene conversion (Fig. 4.4).
Both involve the mismatching of DNA sequences, for which repetitive sequences are usually
responsible [234]. For effective gene conversion,
the homologous sequence must be at least 200 bp
long [249]. In crossing-over, chromatid segments
are exchanged during meiosis, or also during
mitosis if mitotic chromosome pairing takes