Biology Reference
In-Depth Information
independently derived, perhaps by the
convergent evolution
(Chapter 4, section 4.3)
of placenta-specific enhancer elements. Support for this postulate has come from a
comparison of human and equine chorionic gonadotropin
-chain (
CGA
; 6q21.1-
q23) gene promoter sequences (Steger
et al
., 1991). The human gene contains a tro-
phoblast-specific element (TSE) and two copies of a cAMP response element
(CRE) all of which are required for full placental expression. Both the CRE and
TSE are bound by the leucine zipper-containing protein, CREB. By contrast,
cAMP regulation of the equine
Cga
gene is not mediated by CREB but instead by
aACT, a GATA-related protein that binds to the promoter at a site distinct from the
CREB-binding site. It would thus appear as if the conversion of the
CGA
gene
from being pituitary-specific to being also placentally expressed was a consequence
of independent evolutionary processes in primates and horses.
In the New World monkey,
Cebus apella
, the
2-globin (
HBG2
) gene is
expressed at a 20-fold higher level than the closely linked
1-globin (
HBG1
) gene
(Johnson
et al
., 1996). The most obvious difference between the promoters of the
two genes and the one most likely to account for the difference in expression, is a
CCAAC motif instead of the canonical CCAAT found in the
HBG1
promoter
(Chiu
et al
., 1996). Intriguingly, the
HBG1
gene has been inactivated by deletion
in the Atelidae whereas in the Pitheciini, the CCAAT box has been changed to
CCGAT (Chiu
et al
., 1996). In the New World monkey
Aotus azarae
, a single
hybrid
HBG
gene has been created as a result of an unequal crossing over event
(Chiu
et al
., 1996); this gene possesses the promoter and 5
UTR of the
HBG1
gene
coupled to the coding region of the
HBG2
gene. Why the
HBG1
gene has been
inactivated several times independently in platyrrhines is unclear; expression
from both
HBG1
and
HBG2
genes has been preserved in catarrhines (Chapter 4,
section 4.2.1,
Globin genes
).
The human prolactin (
PRL
; 6p22) gene possesses two promoters, the proximal
one reponsible for directing expression in the anterior pituitary, the distal one for
expression in the decidualized endometrium and the mammary gland. Sequences
homologous to both promoters are present in the rat
Prl
gene promoter but the
distal sequence is nonfunctional (Shaw-Bruha
et al
., 1998). Whether the human
PRL
gene has gained a functional promoter in the last 100 Myrs since the diver-
gence of our common ancestors, or whether the distal promoter in the rat gene has
ceased to function during this time, is unclear.
Other examples of inter-specific differences in orthologous promoter regions
include the thymidine kinase 1 (
TK1
; 17q25.2-q25.3) gene promoter which con-
tains functional CCAAT elements in humans, chickens and Chinese hamsters but
not in mice and rats (Arcot
et al
., 1991) and the osteonectin (
SPARC
; 5q31-q32)
gene promoter whose GGA-box sequences contribute to cell-type specific expres-
sion in human but not in the bovine (Hafner
et al
., 1995). The mammalian
SPARC
gene also differs from its
Xenopus
counterpart in that the latter contains a
TATA box but lacks a GGA-box (Damjanovski
et al
., 1998).
Various species-specific sequence differences have also been reported in nuclear
factor binding sites in the promoter regions of the
D7Rp2e
genes in
Mus domesti-
cus
and
M. pahari
that alter both the pattern of binding site occupancy and the
ability of the bound factors to repress transcription (Singh and Berger, 1998;
Singh
et al
., 1998).
