Biology Reference
In-Depth Information
the
CYP17
and
CYP21
genes or the
CYP11
,
CYP24
, and
CYP27
genes. The phy-
logeny of the cytochrome P450 superfamily has been explored to some extent and
various attempts have been made to date the various gene duplication events
which have given rise to extant genes (Degtyarenko and Archakov, 1993; Nelson
and Strobel, 1987; Nebert et al., 1989). Much of the increase in CYP P450 gene
number took place around 400 Myrs ago. This was the time when tetrapods first
began to colonize the land and feed upon the plants that had become established
in the late Silurian and early Devonian periods. Since these terrestrial plants
probably contained toxic compounds, expansion of the CYP P450 gene family to
provide a large set of detoxifying enzymes was probably an adaptive response to
this chemical challenge.
The
CYP51
gene encodes sterol 14-
-demethylase which plays an important
role in sterol biosynthesis in fungi and plants as well as animals. As such,
CYP51
is the only P450 family member which is recognizable across all eukaryotic phyla
(Rozman
et al
., 1996). The
CYP51
gene also appears to have its counterparts in
prokaryotes (Aoyama
et al
., 1998) and the gene family may have originated before
the divergence of the eukaryotic and prokaryotic kingdoms. When members of
the various mammalian and fungal P450 gene families were aligned and com-
pared (Rozman
et al
., 1996), more than 80 intron locations were identified. Since
it is unlikely that all of these introns were present in the primordial eukaryotic
P450 gene, it may be concluded that P450 gene structures have evolved very con-
siderably over the last 2 billion years either by intron insertion (Chapter 3, section
3.5) or intron sliding (Chapter 3, section 3.4).
Cystatin genes.
The cystatin superfamily comprises a number of proteins, many
of which are cysteine protease inhibitors, but which have evolved to take on a
variety of different physiological functions (Rawlings and Barrett, 1990). The
family has emerged through a process of duplication and divergence from a pri-
mordial gene which is thought to have existed more than 1200 Myrs ago
(Rawlings and Barrett, 1990). Human cystatin superfamily genes belong to family
1 [cystatins A and B (
CSTA
, 3cen-q21;
CSTB
, 21q22.3)], family 2 cystatins C, S,
SA and SN (
CST3
,
CST4
,
CST2
, and
CST1
; 20p11.2; Thiesse et al., 1994), family
3 kininogen (
KNG
, 3q21-qter) or family 4 histidine-rich glycoprotein and
α
2
HS-
glycoprotein (
HRG
, 3q27;
AHSG
, 3q27-q29). The evolutionary relationship of
these genes remains to be unravelled (Brown and Dziegielewska, 1997; Müller-
Esterl
et al.
, 1985).
G-protein-coupled receptor genes.
The G-protein-coupled receptor (GPCR)
superfamily can be separated into five different groups on the basis of their nat-
ural ligands: (i) peptides and peptide hormones, for example endothelin receptors
(
EDNRB
, 13q22;
EDNRA
, chromosome 4), adrenocorticotropic hormone recep-
tor (
MC2R
; 18p11.2), angiotensin receptor (
AGTR1
; 3q21-q25), thyrotropin
receptor (
TSHR
; 14q31), (ii) neurotransmitters, for example dopamine receptors
(
DRD1
, 5q35;
DRD2
, 11q23;
DRD3
, 3q13;
DRD4
, 11p15;
DRD5
, 4p15-p16),
(iii) other regulatory factors, for example thrombin receptor (
F2R
; 5q13), (iv) sen-
sory stimuli, for example opsins (see Chapter 7, section 7.5.2,
The visual pigments
),
and (v) unknown ligands. The GPCRs are evolutionarily and phylogenetically
