Biology Reference
In-Depth Information
nonhomologous chromosomes are provided by non-reciprocal exchanges between
the X-linked and autosomal phosphoglycerate kinase (
PGK1
, Xq13;
PGK2
; chro-
mosome 19) genes and the X-linked and autosomal pyruvate dehydrogenase
(
PDHA1
, Xp22.1-p22.2;
PDHA2
; 4q22-q23) genes (Fitzgerald
et al
., 1996).
Although gene conversion is generally considered to involve only short
stretches of DNA sequence, it has often not been possible to determine the precise
length of the converted sequence owing to the high degree of homology mani-
fested by the genes involved. Papadakis and Patrinos (1999) reviewed data from
the human G
- (
HBG1
; 11p15.5) globin genes and con-
cluded that the length of the converted fragments is usually less than 400 bp but
can vary from as little as 113 bp to as much as 2266 bp.
The mechanism underlying gene conversion remains elusive but must presum-
ably entail the close physical interaction between homologous DNA sequences. It
may involve heteroduplex formation followed by mismatch repair. Both Amor
et
al
. (1988) and Matsuno
et al
. (1992) have noted the presence of Chi-like sequences
(GCTGGGG; known to promote recombination both in
E. coli
and in mouse
immunoglobulin genes; Smith, 1983) in the vicinity of regions of the
CYP21
/
CYP21P
and
HBB
genes. These authors speculated that the Chi-like
sequences might play a role in gene conversion events. Various other sequences
e.g.
Alu
repeat sequences (Merritt
et al
., 1990), a retroviral Long Terminal Repeat
(Pavelitz
et al
., 1995), alternating purine.pyrimidine tracts (Papadakis and
Patrinos, 1999) and a (CT)
n
- (
HBG2
; 11p15.5) and A
(GA)
n
microsatellite (Liao and Weiner, 1995) have
also been postulated to be involved in promoting gene conversion. Many gene
conversion events involving the
HBG1
and
HBG2
genes appear to terminate near
a polypyrimidine stretch (Fitch
et al
., 1990). Papadakis and Patrinos (1999) sug-
gested that palindromic sequences may be associated with the termination of gene
conversion, possibly through secondary structure formation blocking branch
migration. The insertion of some transposable elements into members of multi-
gene families can however reduce the rate, and limit the extent of, gene conver-
sion by reducing the degree of homology between potential donor and acceptor
sequences (Hess
et al
., 1983; Schimenti and Duncan, 1984).
Gene conversion has thus had an important influence on the evolution of
multigene families by homogenizing the sequences of duplicated or repeated
genes. Sequence homogenization can of course hinder divergence and hence
potential adaptation. New substitutions occurring in a sequence will tend to be
lost because they are likely to be converted back to the sequence of the more com-
mon allele in the population. However, gene conversion may also promote diver-
sity by introducing multiple sequence changes simultaneously into different
members of large gene families as with the genes encoding the proteins of the
major histocompatibility complex (
HLA-B
,
HLA-DRA
; 6p21.3) (Belich
et al
.,
1992; Gorski and Mach, 1986; Kuhner and Peterson, 1992; Kuhner
et al
., 1991;
Ohta, 1991; Parham and Lawlor, 1991; Seemann
et al
., 1986) and the kallikreins
(Ohta and Basten, 1992).
9.6 Gene creation by retrotransposition
A mutation that produces a new elementary species is due to the sudden
appearance or creation of a new element - a new gene. Put in another way, we