Biology Reference
In-Depth Information
important for their coordinate regulation by common control elements (see
Chapter 5, section 5.1.14). The various subunits of the T-cell antigen receptor are
intriguing: the
- and
-subunits are encoded by genes (
TCRA
,
TCRD
) on chro-
mosome 14, the
- and
-subunit genes (
TCRB
,
TCRG
) are on chromosome 7
whereas the
-subunit gene (
TCRE
) lies on chromosome 11. Whilst synteny prob-
ably implies a common evolutionary origin, lack of synteny does not necessarily
argue against it.
Clustering of genes of similar function and common evolutionary origin is common
, for
example the genes encoding blood coagulation factors VII (
F7
) and X (
F10
) on
chromosome 13q34, the
-crystallin (
CRYG
) gene cluster on chromosome 2q33
and the six alcohol dehydrogenase (
ADH1
,
ADH2
,
ADH3
,
ADH4
,
ADH5
,
ADH7
) genes on chromosome 4q22. Many more examples are given in Chapter 4.
Genes do not usually exhibit chromosomal clustering with respect to the structure/func-
tion of particular organs or subcellular organelles
(e.g. mitochondria). However, vari-
ous genes encoding proteins expressed in the course of epidermal differentiation
[involucrin (
IVL
), loricrin (
LOR
), filaggrin (
FLG
), the small proline-rich pro-
teins (
SPRR1A
,
SPRR1B
,
SPRR2A,
and
SPRR3
), trichohyalin (
THH
)] are clus-
tered together on chromosome 1q21 thereby betraying their common
evolutionary origin (Volz
et al
., 1993). A considerable number of the genes encod-
ing various cytokines (including several hematopoietic growth factors) and their
receptors are clustered on the long arm of chromosome 5: granulocyte-
macrophage colony-stimulating factor (
GMCSF
), macrophage colony-stimulat-
ing factor (
CSF2
), the CSF1 receptor (
CSF1R
, colony-stimulating factor-1
receptor, also known as c-
fms
), interleukins 3, 4, 5, 9, 12B, and 13 (
IL3
,
IL4, IL5,
IL9, IL12B, IL13
), platelet-derived growth factor receptor-
(
PDGFRB
), acidic
fibroblast growth factor (
FGF1
) and fibroblast growth factor receptor 4 (
FGFR4
).
The genes encoding the IL3 receptor
-chain (
IL3RA
) and the GMCSF receptor
-chain (
CSF2RA
) both map to the pseudoautosomal region of the sex chromo-
somes. Synteny betrays the common evolutionary origin of the genes as well as
the probable mechanism—tandem duplication.
Genes encoding ligands and their associated receptors are sometimes syntenic
, for
example the genes encoding transferrin (
TF
) and its receptor (
TFRC
) are both
located on chromosome 3q whilst the genes encoding apolipoprotein E (
APOE
)
and the low density lipoprotein receptor (
LDLR
) are both located on chromo-
some 19. However, not surprisingly, this is far from always the case, for example
insulin (
INS,
chromosome 11) and insulin receptor (
INSR,
chromosome 19); epi-
dermal growth factor (
EGF,
chromosome 4), epidermal growth factor receptor
(
EGFR,
chromosome 7); growth hormone (
GH1, GH2
, chromosome 17) and
growth hormone receptor (
GHR
, chromosome 5); interferons
1
(
IFNA, IFNB1, IFNG
,
IFNW1
, chromosomes 9, 8 and 9, 12, 9), interferon recep-
tors
,
,
and
(
IFNAR1, IFNGR1
, chromosome 6).
The linear order of members of a family of related genes can reflect the order in which
they become activated during development
, for example the
HBE1
(embryonic),
HBG2, HBG1
(fetal),
HBD, HBB
(postnatal) genes of the human
/
/
and
-globin clus-
ter. The expression of these genes is controlled by an upstream locus control
region (LCR; see section 1.1.2,
Locus control regions
) and correct gene order is
required for the normal temporal pattern of developmental expression
