30
2 Nucleic Acids and Nuclear Proteins
The question of the homology of the histones is
difficult to answer because of their monotonous
amino acid composition; it is apparent, however,
that at least histones H2A, H2B and H4 share a
common origin. It is controversial whether H3
also belongs to this group. Hl is different to the
core histones in almost every respect and is
undoubtedly not homologous [486]. The core histones have changed only slowly during evolution,
H3 and H4 being amongst the most conserved
proteins (see Table 4.12; p. 161). The sequence of
H4 is constant throughout the vertebrates, and
differs in sea urchins, starfish and the nematode
Caenorhabditis elegans by only one amino acid,
and in higher plants by only two amino acids
[451]. The H3 sequence of mammals differs by
only one amino acid from that of the rainbow
trout, Salmo gairdneri, and by only four amino
acids from those of Caenorhabditis elegans and
peas [87,451]. The most unusual core histones
are found in the Ciliophora: the H4 of Tetrahymena thermophila shows only 78 % similarity
with that of yeast, and only 80 % similarity with
the higher eukaryotes. This provides one of the
arguments in support of the idea that the ciliates
diverged from the general evolutionary line of the
eukaryotes prior to the separation of the fungi,
higher plants and animals [201].
Histones H2A and H2B show strong species
specificity. Compared with the corresponding histones from calf thymus, the H2A from the rainbow trout differs in 6 positions, from the cephalopod Sepia officinalis and the worm Sipcinculus
nudus in 19 positions, and from Caenorhabditis
elegans in 23 positions; the H2B from the trout
Salmo trutta differs in 8 positions, from Drosophila in 21 positions and from the limpet Patella in
26 positions [87, 233, 451,479]. Hl is evolutionarily much less conserved than the core proteins
and may be represented within a single animal by
several cell-specific variants [485]. The Cterminal regions of histones H2A and H2B, in
agreement with the requirements for stable
protein-protein binding, show much less variation
than the N-terminal regions, which must be
adapted to different DNA sequences and activities in different cells, chromosomes or chromosome regions. For similar reasons, the central section of the Hl histone is much more highly conserved than are the terminal regions [451, 479,
485]. In addition to substitution and deletion of
individual amino acids, the evolution of the histones has also involved the duplication, insertion or
deletion of longer sequences, as will be described
for several sperm-specific Hl and H2B histones.
2.5.2 The Histone Genes
In completely differentiated cells, the histones
are subject to a turnover process, the rate of
which is greater for the various Hl types than it is
for the core histones. Thus, the half-lives of histones Hl° and HIA in mouse kidney cells are 41
and 61 h, those of H2B and H2A are 90 and 135 h,
and those of H3 and H4 are as high as 216 and
316 h, respectively [110]. The most intensive histone synthesis occurs more or less simultaneously
with DNA replication in the S-phase of the cell
cycle. Chromatin doubling requires large quantities of histones, e.g. in mammalian cells about
30 million molecules of each histone type are
needed. Hence, all eukaryotes possess multiple
genes for the five histone classes, with several
hundred copies in sea urchins, 660 copies in the
polychaete Platynereis dumerilii, 120-140 copies
in Drosophila hydei, 100-110 copies in D. melanogaster, 11 copies in Caenorhabditis elegans, 145
copies in the rainbow trout Salmo gairdneri, 90
copies in the clawed frog Xenopus laevis, 10
copies in the chicken, 10-20 copies in mice, and
only 2-3 copies in Tetrahymena [86, 240, 364, 391,
443, 485]. The different copy numbers may be
explained by the fact that the successive cell divisions in the early embryo development of sea
urchins and Drosophila follow much more rapidly
than in vertebrates. The number of histone genes
in the Urodela increases out of proportion to the
C value; the crested salamander, Triturus cristatus, (C = 23 pg) has 636 H4 genes, and the axolotl, Ambystoma mexicanum, (C = 38 pg) has
2685; nevertheless, it is questionable whether all
these genes are active [194].
The histone genes of Tetrahymena are dispersed throughout the genome, whereas in yeast
they are organized into four gene pairs, H2AH2B and H3-H4 [21]. In contrast, most of the histone genes of Drosophila and the histone genes
expressed early in sea urchin embryo development are arranged in highly organized clusters
that contain one gene of each of the five histone
classes in a tandem array. The order of the genes
within the clusters is species specific but uniform
within each genome; the individual histone
genes, however, may be read in different directions (Fig. 2.7). Gene clusters lacking Hl genes are
found in the starfish (H2B-H2A-H4-H3) and the
polychaete Platynereis (H4-H2B-H2A-H3) [88,
391]. The organization of the gene clusters in vertebrates is much less regular: the clusters mostly
do not lie in tandem; the number and order of the
genes within the cluster of anyone animal may
2 Nucleic Acids and Nuclear Proteins
The question of the homology of the histones is
difficult to answer because of their monotonous
amino acid composition; it is apparent, however,
that at least histones H2A, H2B and H4 share a
common origin. It is controversial whether H3
also belongs to this group. Hl is different to the
core histones in almost every respect and is
undoubtedly not homologous [486]. The core histones have changed only slowly during evolution,
H3 and H4 being amongst the most conserved
proteins (see Table 4.12; p. 161). The sequence of
H4 is constant throughout the vertebrates, and
differs in sea urchins, starfish and the nematode
Caenorhabditis elegans by only one amino acid,
and in higher plants by only two amino acids
[451]. The H3 sequence of mammals differs by
only one amino acid from that of the rainbow
trout, Salmo gairdneri, and by only four amino
acids from those of Caenorhabditis elegans and
peas [87,451]. The most unusual core histones
are found in the Ciliophora: the H4 of Tetrahymena thermophila shows only 78 % similarity
with that of yeast, and only 80 % similarity with
the higher eukaryotes. This provides one of the
arguments in support of the idea that the ciliates
diverged from the general evolutionary line of the
eukaryotes prior to the separation of the fungi,
higher plants and animals [201].
Histones H2A and H2B show strong species
specificity. Compared with the corresponding histones from calf thymus, the H2A from the rainbow trout differs in 6 positions, from the cephalopod Sepia officinalis and the worm Sipcinculus
nudus in 19 positions, and from Caenorhabditis
elegans in 23 positions; the H2B from the trout
Salmo trutta differs in 8 positions, from Drosophila in 21 positions and from the limpet Patella in
26 positions [87, 233, 451,479]. Hl is evolutionarily much less conserved than the core proteins
and may be represented within a single animal by
several cell-specific variants [485]. The Cterminal regions of histones H2A and H2B, in
agreement with the requirements for stable
protein-protein binding, show much less variation
than the N-terminal regions, which must be
adapted to different DNA sequences and activities in different cells, chromosomes or chromosome regions. For similar reasons, the central section of the Hl histone is much more highly conserved than are the terminal regions [451, 479,
485]. In addition to substitution and deletion of
individual amino acids, the evolution of the histones has also involved the duplication, insertion or
deletion of longer sequences, as will be described
for several sperm-specific Hl and H2B histones.
2.5.2 The Histone Genes
In completely differentiated cells, the histones
are subject to a turnover process, the rate of
which is greater for the various Hl types than it is
for the core histones. Thus, the half-lives of histones Hl° and HIA in mouse kidney cells are 41
and 61 h, those of H2B and H2A are 90 and 135 h,
and those of H3 and H4 are as high as 216 and
316 h, respectively [110]. The most intensive histone synthesis occurs more or less simultaneously
with DNA replication in the S-phase of the cell
cycle. Chromatin doubling requires large quantities of histones, e.g. in mammalian cells about
30 million molecules of each histone type are
needed. Hence, all eukaryotes possess multiple
genes for the five histone classes, with several
hundred copies in sea urchins, 660 copies in the
polychaete Platynereis dumerilii, 120-140 copies
in Drosophila hydei, 100-110 copies in D. melanogaster, 11 copies in Caenorhabditis elegans, 145
copies in the rainbow trout Salmo gairdneri, 90
copies in the clawed frog Xenopus laevis, 10
copies in the chicken, 10-20 copies in mice, and
only 2-3 copies in Tetrahymena [86, 240, 364, 391,
443, 485]. The different copy numbers may be
explained by the fact that the successive cell divisions in the early embryo development of sea
urchins and Drosophila follow much more rapidly
than in vertebrates. The number of histone genes
in the Urodela increases out of proportion to the
C value; the crested salamander, Triturus cristatus, (C = 23 pg) has 636 H4 genes, and the axolotl, Ambystoma mexicanum, (C = 38 pg) has
2685; nevertheless, it is questionable whether all
these genes are active [194].
The histone genes of Tetrahymena are dispersed throughout the genome, whereas in yeast
they are organized into four gene pairs, H2AH2B and H3-H4 [21]. In contrast, most of the histone genes of Drosophila and the histone genes
expressed early in sea urchin embryo development are arranged in highly organized clusters
that contain one gene of each of the five histone
classes in a tandem array. The order of the genes
within the clusters is species specific but uniform
within each genome; the individual histone
genes, however, may be read in different directions (Fig. 2.7). Gene clusters lacking Hl genes are
found in the starfish (H2B-H2A-H4-H3) and the
polychaete Platynereis (H4-H2B-H2A-H3) [88,
391]. The organization of the gene clusters in vertebrates is much less regular: the clusters mostly
do not lie in tandem; the number and order of the
genes within the cluster of anyone animal may