Biology Reference
In-Depth Information
recombination-mediated duplication include those encoding saposin C (
PSAP
;
10q; Rorman
et al
., 1992), pepsinogen A3 (
PGA3
; 11q13; Evers
et al
., 1989), man-
nose-binding protein (
MBP
; 10q11-q21; Sastry
et al
., 1989) and the
-amylase
genes (
AMY1A
,
AMY1B
,
AMY1C
,
AMY2A
,
AMY2B
; 1p21; Groot
et al
., 1990).
Recombination events have also been invoked to explain cases of gene fusion (see
Section 9.3).
Multiple independent recombination events are thought to have occurred dur-
ing the evolution of the two human haptoglobin genes (
HP
and
HPR
; 16q22.1)
and their counterparts in the other primates (Erickson
et al
., 1992; Erickson and
Maeda 1994; Maeda
et al
., 1986; Maeda, 1985; McEvoy and Maeda, 1988). Whilst
the great apes and Old World monkeys possess three haptoglobin genes (
Hp
,
Hpr,
and
Hpp
), New World monkeys only have one (
Hp
). This is consistent with a gene
triplication after the divergence of Old World from New World monkeys followed
by a
Hpp
gene deletion in the human lineage. Breakpoint analysis suggests that
both duplications and deletions of gene copies may have been mediated by
homologous unequal recombination between
Alu
repeats. That this region is
prone to recombination is also evidenced by the haptoglobin gene copy number
polymorphism found in the black population (Maeda
et al
., 1986). Other examples
of homologous recombination events thought to be responsible for human gene
copy number polymorphisms include the
-globin (
HBA1
; Lie-Injo
et al
., 1981)
genes, the
-amylase genes
(Groot
et al
., 1989), the proline-rich protein genes (
PRB1, PRB2, PRB3, PRB4
;
12p13.2; Lyons
et al
., 1988) and the pepsinogen A genes (
PGA3
,
PGA4
,
PGA5
;
11q13; Zelle
et al
., 1988); none of these copy number polymorphisms are known
to have any clinical significance.
Recombination has also resulted in the alteration of the expression level of a
gene. Thus, the galago
-globin (
HBZ
; Winichagoon
et al
., 1982) gene, the
-globin gene is expressed at an unusually high level in the
adult (18% of
-like globin chains, cf. 0-6% in other primates) as a result of a
recombination event which replaced 2.4 kb of
-globin
gene sequence containing 800 bp of the promoter region (Tagle
et al
., 1991).
Considerable effort has been made to localize and characterize the DNA
sequences responsible for mediating the recombinational events known to have
occurred during gene evolution. Thus, the duplication events involved in the evo-
lution of the human glycophorin (
GYPA, GYPB,
and
GYPE
; 4q28.2-q31.1) genes
(Labuda
et al
., 1995;
Figure 9.7
), the human growth hormone gene (
GH1, GH2,
CSH1, CSH2
; 17q22-q24; Figure 4.13) cluster (Chen
et al
., 1989) and the mouse
lysozyme genes (Cross and Renkawitz, 1990) are considered to have been medi-
ated by recombination between
Alu
repeats. A correspondence between illegiti-
mate recombination junctions and the sites of
Alu
sequence insertion has also
been proposed for the primate
-globin gene sequence by
-globin (
HBA1
,
HBA2
; 16p13.3) genes (Bailey
et al
., 1997; Shaw
et al
., 1991). The duplication of the primate
-globin (
HBG1
;
11p15.5) gene may have been mediated by homologous recombination between
LINE elements flanking a fetal globin progenitor gene (Fitch
et al
., 1991). High
G+C content may promote recombination (Eyre-Walker, 1993) whilst Ashley
et al
. (1993) have suggested that telomeric repeats could promote meiotic
recombination.
