Biology Reference
In-Depth Information
8.5.3 Tandem duplications
Multigene families often form syntenic gene clusters as a result of the tandem
duplication of an ancestral gene sequence. For example, the immunoglobulin
genes are clustered at 14q32.33 (
IGHA
,
IGHD
,
IGHG
) and 22q11.2 (
IGLC
,
IGLL
) (see Chapter 4, section 4.2.4,
Immunoglobulin genes
), the T-cell receptor
genes at 14q11.2 (
TCRA
,
TCRD
), 7q35 (
TCRB
) and 7p14-p15 (
TCRG
) (see
Chapter 4, section 4.2.4,
T-cell receptor genes
), the pregnancy-specific glycoprotein
(
PSG1
,
PSG2
,
PSG3
,
PSG4
,
PSG5
,
PSG6
,
PSG7
,
PSG8
,
PSG11
,
PSG12
,
PSG13
) genes at chromosome 19q13.2, the histocompatibility antigen (
HLA
)
genes at chromosome 6p21.3 (see Chapter 4, section 4.2.1,
Genes of the major histo-
compatibility complex
) whilst the three alkaline phosphatase genes (
ALPP
,
ALPI
,
ALPPL2
) are clustered at chromosome 2q37.
Some genes appear especially prone to duplicate, probably by virtue of their
already being clustered in multiple copies. Thus, the carcinoembryonic antigen
(
PSG
,
CEA
; 19q13.2) gene family has undergone multiple, but independent, mul-
tiplication events in both the rodent and primate lineages (Rudert
et al
., 1989). In
similar vein, a disproportionate fraction of mapped zinc finger gene family mem-
bers are located on chromosome 19 (Lichter
et al
., 1992; Chapter 4, section 4.2.3,
Zinc finger genes
). Such clustering has probably arisen as a result of the serial
duplication of a single ancestral gene on the same chromosome.
Members of gene families in different species may however be amplified differ-
entially. For example, in the human genome, three members of the formylpeptide
receptor gene family (
FPR1
,
FPRL1,
and
FPRL2
) cluster at chromosome
19q13.3, whereas in mouse, there are six
Fpr
genes on a syntenic region of chro-
mosome 17 (Gao
et al
., 1998). The human
FPRL2
gene and four murine
Fpr
genes
arose after the divergence of human and mouse.
8.5.4 Translocation of duplicated genes
Gene family members have often become chromosomally separated through
translocation (Chapter 9, section 9.2) and it would appear as if the older the multi-
gene family, the more likely this is to happen. Thus, the chromosomally unlinked
CD36L2
(chromosome 4),
CD36L1
(chromosome 12) and
CD36
(7q11.2) mem-
brane glycoprotein genes were duplicated and diverged from an ancestral gene
prior to the separation of the arthropod and vertebrate lineages (Calvo
et al
., 1995).
Other examples of ancient duplicated genes that have become separated by
translocation are the thrombospondin (
THBS1
, 15q15 and
THBS2
, 6q27) genes
which arose ~900 Myrs ago (Lawler
et al
., 1993) and the transforming growth fac-
tor-
(
TGFB1
, 19q13.2;
TGFB2
, 1q41;
TGFB3
, 14q24) genes which arose ~300
Myrs ago (Burt and Paton, 1992).
8.5.5 Duplication of translocated genes
Genomic duplication may be followed by further local tandem duplication as
exemplified by the human homeobox gene clusters at 7p14-p15 (
HOXA
), 17q21-
q22 (
HOXB
), 12q12-q13 (
HOXC
) and 2q31 (
HOXD
) (see Chapter 4, section 4.2.1,
Homeobox genes
). The same phenomenon is exhibited by the human sodium
