Biology Reference
In-Depth Information
The
- and
-globin genes diverged from the
/
ancestral gene about 100 Myrs ago
(
Figure 4.11
) followed by the duplication of the
γ
genes, an event which occurred before the divergence of the Old World and New
World monkeys (Chiu
et al
., 1997; Slightom
et al
., 1987). The human
-globin gene to form the G
and A
-globin gene
cluster (11p15.5) therefore comprises the embryonically expressed
(
HBE1
) gene,
the fetal G
(
HBG2
) and A
(
HBG1
) genes, the post-natally expressed
(
HBB
)
and
(
HBD
) genes plus a single
pseudogene (
HBBP1
) (
Figure 4.12
). Thus, as
with the
-globin genes, the genes in the 75 kb
-globin gene cluster are arranged
in the order of their activation during ontogeny.
The
HBD
gene is present in humans, apes and New World monkeys but has
been inactivated in Old World monkeys (Kimura and Takagi, 1983; Martin
et al
.,
1980). During evolution, gene conversion has operated on the
HBD
gene allow-
ing it to acquire sequence characteristics of the
HBB
gene (Koop
et al
., 1989; Tagle
et al
., 1991). Gene conversion events have however been even more frequent
between the
HBG2
and
HBG1
genes (Chiu
et al
., 1997; Slightom
et al
., 1987;
1988). In addition to gene conversion, a number of other events have occurred
during evolution which have altered the
-globin cluster in specific ways in dif-
ferent mammalian orders; these include insertion of repeat sequences, change in
expression profile, gene duplication, gene fusion and gene loss or inactivation
(
Figure 4.13
). Thus, the lagomorphs and rodents lack the
-globin locus whilst the
artiodactyls lack the
-globin locus. As a consequence of some of these changes,
the
-globin cluster in mammals varies from as little as 20 kb in lemurs to about
90 kb in goats (
Figure 4.13
).
The
globin genes were originally embryonically expressed and fetally
inactive and this early expression pattern is still found in the galago and lemurs
(Tagle
et al
., 1988). In higher primates, the
and
-globin gene was duplicated before the
divergence of Old World and New World monkeys (perhaps by an unequal homol-
ogous crossing over event mediated by LINE elements; Fitch
et al
., 1991) and
became fetally expressed as a direct result of the accumulation of sequence
changes in the 5
flanking region (Johnson
et al
., 1996; TomHon
et al
., 1997). In
Old World monkeys, apes and humans, both the
1- and
2-globin genes are func-
tional but the expression of the
1 gene is three-fold higher than that of the
2
gene. In New World monkeys, only one
-globin gene is functional, usually
2
(Chiu
et al
., 1996; 1997; Johnson
et al
., 1996; Meireles
et al
., 1995).
Growth hormone and somatomammotropin genes.
The growth hormone
and prolactin genes are thought to have emerged as a result of a duplication
event some 470 Myrs ago. In nonprimates, with the exception of caprine rumi-
nants (Wallis
et al
., 1998), GH is encoded by a single gene whilst in primates, the
gene has expanded to a gene cluster. Thus, the human gene encoding pituitary-
expressed growth hormone (
GH1
) is located on chromosome 17q23 within a
cluster of five related genes (Chen
et al
., 1989). The other loci present in the
growth hormone gene cluster are two chorionic somatomammotropin genes
(
CSH1
and
CSH2
), a chorionic somatomammotropin pseudogene (
CSHP1
) and
a second growth hormone gene (
GH2
). These genes are separated by intergenic
regions of 6 kb to 13 kb in length, lie in the same transcriptional orientation, are
placentally expressed and are under the control of a downstream tissue-specific
