Biology Reference
In-Depth Information
gene locus control region is conserved between placental mammals, marsupials
and monotremes (Hardison
et al
., 1997) but the spacing between the elements dif-
fers between species.
5.1.2 Nonhomologous genes containing similar regulatory elements
Some
cis
-acting elements are common to a wide variety of different genes and may
be evolutionarily very ancient. Thus, the TGTGACGTCTTTCAGA cAMP-
responsive element in the promoter of the human vasoactive intestinal polypep-
tide (
VIP
; 6q26-q27) gene is similar not only to elements found in the promoters
of nonorthologous murine and avian genes but also to sequences described in
yeast and adenoviral promoters and to the
E. coli
consensus sequence recognized
by the cAMP receptor protein (Lin and Green, 1989).
Even if we confine ourselves to the same species, completely unrelated genes
often also possess similar upstream regulatory elements. Thus, the promoters of
the human E-selectin (
SELE
; 1q22-q25) and
-interferon (
IFNB1
; 9p22) genes
both contain NF
B, ATF-2 and HMG I(Y) binding sites (Whitley
et al
., 1994).
Other examples of promoter similarity include the serum response elements pre-
sent in the regulatory regions of the human apolipoprotein E (
APOE
; 19q13.2), c-
fos
-actin (
ACTB
; 7p12-p15) genes or the
AGGCGGCCCTTT motif in the apolipoprotein B (
APOB
; 2p24), apolipoprotein
CIII (
APOC3
; 11q23-qter) and
(
FOS
; 14q24.3), and
1-antitrypsin (
PI
; 14q32.1) genes (Surguchov,
1991). It is as yet unclear if these elements have evolved by the slow fine tuning of
existing sequences or if they have instead been introduced by promoter shuffling.
5.1.3 Paralogous genes containing dissimilar regulatory elements
Evolutionarily related genes in the same organism often differ in their expression
profiles. Thus, the various paralogous members of the family of murine
cytochrome P450-16 (testosterone 16-
-hydroxylase) genes are evolutionarily
related yet are regulated quite differently (Wong
et al
., 1989). Similarly, the chro-
mosomally unlinked human annexin I (
ANX1
; 9q11-q22), VI (
ANX6
; 5q32-q34),
and VII (
ANX7
; 10q21.1-q21.2) genes are evolutionarily related and encode pro-
teins that are structurally and biochemically very similar. However, these genes
possess very different sets of promoter and enhancer elements which are presum-
ably responsible for their distinct patterns of tissue expression (Donnelly and
Moss, 1998; Shirvan
et al
., 1994). Can we relate differences in expression profile of
paralogous genes to changes in upstream regulatory elements?
A number of studies of paralogous gene promoters have been performed and
differences in promoter sequence between members of the same multigene family
have indeed been found that may account for differences in transcriptional effi-
ciency. Some paralogous promoters differ with respect to the presence or absence
of specific regulatory elements. Others differ in terms of more subtle single base-
pair substitutions introduced into specific
cis
-acting motifs which serve to
increase or decrease the binding affinity of their cognate transcription factors.
Such changes in promoter structure have contributed to post-duplicational gene
diversification by providing the divergent gene products with their own specific
