Biology Reference
In-Depth Information
chromosome 1p21) but sometimes not (e.g. cardiac (
ACTC
), skeletal muscle
(
ACTA1
), smooth muscle, aorta (
ACTA2
) and smooth muscle, enteric (
ACTG2
)
-actin genes which are located on chromosomes 15, 1, 10, and 2, respectively).
Again, the time that has elapsed since the duplication event is likely to be an
important factor in determining whether or not the duplicated genes have
remained syntenic.
Genes encoding isozymes specific for different subcellular compartments are usually not
syntenic
[e.g. soluble/extracellular and mitochondrial forms of superoxide dismu-
tase (
SOD1
/
SOD3
,
SOD2
on chromosomes 21/4 and 6, respectively), aconitase
(
ACO1
,
ACO2
on chromosomes 9 and 22) and thymidine kinase (
TK1
,
TK2
on
chromosomes 17 and 16)].
Genes encoding enzymes catalyzing successive steps in a particular metabolic pathway are
usually not syntenic
. Thus, the five enzymes of the urea cycle are encoded by genes
(
ARG1, ASL, ASS, CPS1, OTC
) on chromosomes 6, 7, 9, 2, and X and four
enzymes involved in galactose metabolism are encoded by genes (
GALE, GALK1,
GALK2, GALT
) on chromosomes 1, 17, 15, and 9. However, there are exceptions to
this rule: four genes encoding enzymes of the glycolytic pathway (
TPI1, GAPD,
ENO2, LDHB
) are located on the short arm of chromosome 12 in the region p13-
p12. Similarly, the
GDH
and
PGD
genes encoding enzymes of the phosphoglu-
conate pathway are encoded by linked genes on chromosome 1. The reasons for this
syntenic organization, when it occurs, are usually unclear but we may nevertheless
surmise the evolutionary history of the genes involved. Indeed, as early as 1945,
Horowitz proposed that genes encoding enzymes of metabolic pathways could have
arisen by serial duplication. His idea was that the protein that would eventually
become the terminal enzyme of a given metabolic pathway would possess a binding
site for the substrate that it used. A novel protein derived from the duplicated gene
could still use this binding site for interaction with the same substrate molecule but
could evolve the capability of producing it as a product from another source. Thus,
the substrate for the terminal enzyme would become an intermediate in the devel-
oping metabolic pathway. In this way, the various enzymes of a pathway would
evolve from each other in the reverse order to that in which they appear in the mod-
ern pathway. The synteny observed in the cases cited above might be a consequence
of conservation resulting from a requirement for coordinate regulation of the loci
concerned. Some of these principles also appear to hold for the genes encoding the
enzymes of the coagulation cascade (see Chapter 10).
Genes encoding different subunits of a heteromeric protein are often not syntenic
(e.g. the
genes encoding
-globin (
HBB,
chromosome 11), lactate dehydrogenases A (
LDHA,
chromosome 11) and B
(
LDHB,
chromosome 12), factor XIII subunits a (
F13A,
chromosome 6) and b
(
F13B,
chromosome 1), the immunoglobulin light chains (
IGK, IGL
, chromo-
somes 2 and 22), and heavy chains (
IGH
, chromosome 14). However, several cases
of synteny are known e.g. the genes encoding the three chains of fibrinogen (
FGA,
FGB, FGG,
all closely linked on chromosome 4), the
-globin (
HBA1, HBA2
, chromosome 16) and
-chains of C4b-bind-
ing protein (
C4BPA
and
C4BPB,
closely linked on chromosome 1q32), the com-
plement component 1Q
- and
-chains (
C1QA, C1QB
, linked on chromosome
1p) and the platelet membrane glycoproteins IIb and IIIa (
ITGA2B, ITGA3,
closely linked on chromosome 17q21-q22). The clustering of these genes may be
- and
