Biology Reference
In-Depth Information
9.5 Gene conversion
Gene conversion is the 'modification of one of two alleles by the other' (Vogel and
Motulsky, 1997). The end result is very similar to that resulting from a double
unequal crossing-over event and in humans, it is difficult to distinguish the two
processes (Cooper and Krawczak, 1993). However, in practical terms, the differ-
ence is that the correction of an 'acceptor' gene or DNA sequence by gene con-
version is nonreciprocal leaving the 'donor' sequence physically unchanged.
The process of gene conversion may involve the whole or only a part of a gene
(Dover, 1993) and usually occurs between highly homologous, but nonallelic
genes. Gene conversion may be suspected in cases where the degree of sequence
homogeneity exhibited by related genes is much greater than expected from what
is known of their evolutionary history. Thus, two or more gene sequences may
exhibit strong homology over all or parts of their coding or promoter sequences
yet they are known from phylogenetic studies to have diverged a considerable
time ago and might reasonably have been expected to have accumulated signifi-
cant numbers of both synonymous and non-synonymous substitutions.
There are now numerous examples of gene conversion causing human gene
pathology (Cooper and Krawczak, 1993; see Chapter 6, section 6.1.6) but gene
conversion has also had an important influence in evolution. Examples of gene
conversion in human gene evolution often involve duplicated gene sequences
lying in close physical proximity: the G-γ (
HBG2
; 11p15.5) and A-γ (
HBG1
;
11p15.5) globin genes (Shen
et al
., 1981; Scott
et al
., 1984; Stoeckert
et al
., 1984;
Powers and Smithies, 1986; Fitch
et al
., 1990; see
Figure 9.9
), the β - and δ -globin
genes (
HBB
,
HBD
; 11p15.5; Koop
et al
., 1989), the α 1-(
HBA1
) and α 2-(
HBA2
)
globin genes (Liebhaber
et al
., 1981), the
HLA-DQB1
loci (6p21.3; Wu
et al
.,
1986), the visual pigment (
GCP
and
RCP
; Xq28; Kuma
et al.,
1988; Shyue
et al
.,
1994; 1995; Winderickx
et al
., 1993; Zhou and Lee, 1996) genes, the rhesus blood
group (
RHD
,
RHCE
; 1p34-p36.2; Carritt
et al
., 1997) genes, the salivary
(
AMY1A
,
AMY1B
,
AMY1C
; 1p21) and pancreatic (
AMY2A
and
AMY2B
; 1p21)
amylase genes (Gumucio
et al
., 1988), the α -interferon genes
IFNA1
and
IFNA13
(9p22; Todokoro
et al
., 1984), the haptoglobin genes (
HP
,
HPR
; 16q22.1;
Erickson and Maeda, 1994; Maeda, 1985), the p15 and p16 cyclin-dependent
kinase inhibitor (
CDKN2B
and
CDKN2A
; 9p21) genes (Jiang
et al
., 1995), the
glycophorin genes
GYPA
and
GYPE
(4q28.2-q31.1; Kudo and Fukuda 1994;
Onda and Fukuda 1995), the P glycoprotein 1 and 3 genes (
PGY1
,
PGY3
; 7q21.1;
van der Bliek
et al
., 1988), the salivary proline-rich protein genes (
PRB1
,
PRB2
,
PRB3
,
PRB4
; 12p13.2; Kim
et al
., 1993), the cardiac α - and β -myosin heavy
chain (
MYH6
,
MYH7
; 14q12; Epp
et al
., 1995) genes, the chorionic somatomam-
motropin (
CSH1
,
CSH2
; 17q22-q24) genes (Hirt
et al
., 1987), the immunoglobu-
lin C
H
α (
IGHA1
and
IGHA2
, 14q32; Kawamura
et al
., 1992) and V
H
genes (
IGHV
,
14q32; Haino
et al
., 1994), and the α
1-acid glycoprotein (
ORM1
,
ORM2
;
9q34.1-34.3) genes (Merritt
et al
., 1990).
In the context of gene conversion, if there is any middle ground between
pathology and evolution, it is probably occupied by the cytochrome P450
CYP2A6
gene (19q13.2). A null
CYP2A6
variant, formed by gene conversion
between the
CYP2A6
gene and the closely linked but inactive
CYP2A7
gene
