Biology Reference
In-Depth Information
locus (Borden
et al
., 1990; Zimmer
et al
., 1990), the immunoglobulin heavy chain
V
H
5 (
GABRA5
) gene
(Ritchie
et al
., 1998) and the neurofibromatosis type 1 (
NF1
) gene (Regnier
et al
.,
1997). The inter-chromosomal duplication and transposition of
NF1
-related
sequences may be related to the presence in the vicinity of
region (Tomlinson
et al
., 1994), the GABA A receptor
-satellite sequences
that could have served to promote their dispersal. The transposition associated
with the immunoglobulin V
light chain locus (
IGKV
; chromosome
2p11.1
chromosome 1; Arnold
et al
., 1995) was directed to a site containing an
ALD
like GCTTTTTGC repeat suggesting that a similar mechanism may have
been responsible for these transpositional events.
The pericentromeric zinc finger gene cluster on chromosome 19p12 which
harbors the
ZNF208
gene is flanked by large blocks of
-satellite repeat sequences
(Eichler
et al
., 1998b). This gene cluster is thought to have arisen early in primate
evolution (~50 Myrs ago) by a process of pericentromeric-directed transposition.
Eichler
et al
. (1998b) proposed a model in which an ancestral
ZNF
gene became
associated with
-satellite repeat sequences at 19p12. Such repeats are capable of
rapid expansion, possibly by unequal crossing over, and may have served to pro-
mote the rapid amplification of the associated
ZNF
gene.
The above examples serve to indicate that the pericentromeric regions of
human chromosomes have frequently acquired sequences from remote genomic
locations. Indeed, these regions appear to be very dynamic, being subject to
amplification, duplication, deletion and inversion events as well as translocations
(Eichler, 1999; Jackson
et al
., 1999). Many of these pericentromeric rearrange-
ments have occurred relatively recently during primate evolution leading to
marked inter-specific differences even among the great apes. The potential evolu-
tionary importance of pericentromeric regions can perhaps be gauged from
Eichler's (1999) description of them as 'recruitment stations for repeats' and
'reservoirs for the accumulation of transposed genic segments.'
9.2.2 Sub-telomeric transposition
Sub-telomeric regions may be similarly dynamic. Thus the rapid proliferation of
multigene families clustered near telomeres may have occurred by repeat-medi-
ated bursts of duplication/transposition of short stretches of genomic DNA (e.g.
the olfactory receptor genes; Trask
et al
., 1998). Duplicational transposition also
resulted in the telomeric localization of a number of pseudogenes derived from
the
Chl1
-related helicase (
DDX11
, 12p11;
DDX12
, 12p13; Amann
et al
., 1996)
and interleukin 9 receptor (
IL9R
; Xq28/Yq12; Kermouni
et al
., 1995) genes. The
'spreading' of a sub-telomeric region has also been described by Monfouilloux
et
al
. (1998); originally localized to 17qter in chimpanzee and orangutan, a specific
sub-telomeric domain has been translocated in humans and has colonized several
other chromosome ends. Finally, there is emerging evidence for sequence
exchange between human telomeric and centromeric regions (Eichler
et al
., 1997;
Jackson
et al
., 1999; Vocero-Akbani
et al
., 1996). This may have had consequences
for the growth and distribution of multigene families as in the case of the human
olfactory receptor genes which, although clustered predominantly in subtelom-
eric regions, are also located in pericentromeric regions (Rouquier
et al
., 1998).
