Biology Reference
In-Depth Information
(a)
RAG1
RAG2
(b)
Receptor
gene exon
'V'
'J'
“V”
“D”
“J”
Gene
duplication
Transposition
events
RAG1 RAG2
V
D
J
C
1
2
'Mammalian'
or
Bind signals
V
D
J
C
V DJ C
V DJ
C
E
xcisio
n
'Cluster'
Figure 9.8.
Model for the evolution of the immunoglobulin and T-cell receptor (TCR)
genes and the role of RAG-mediated transposition (from Agrawal
et al
., 1998).
(a) Putative structure of the recombination activating gene (
RAG
) transposon that
integrated into the germline of a vertebrate ancestor. Arrows denote direction of
transcript. (b) The split organization of extant immunoglobulin and TCR genes may have
arisen by RAG-mediated transposition through the introduction of signal end/signal end
elements into a primordial receptor gene exon, thereby dividing the exon into two or
three gene segments, each flanked by one or two recombination signals (triangles). These
gene segments would be the evolutionary precursors of current V, D, and J gene segments.
Different patterns of gene duplication could have given rise to both the mammalian
heavy chain locus and the 'cluster' configuration in cartilaginous fishes.
within a transposable element that also possessed flanking RSS sequences (
Figure
9.8
). Since in extant genomes, the
RAG
genes and the RSS elements are unlinked,
transposition now serves to relocate pairs of RSS elements plus the intervening
sequence without the necessity of the
RAG
genes themselves being displaced.
The split nature of the vertebrate immunoglobulin light chain and T-cell recep-
tor
genes could have originated from the germline insertion of the RAG
transposon into an ancestral receptor gene soon after the divergence of jawed and
jawless fishes (Agrawal
et al
., 1998; Hiom
et al
., 1998; Thompson, 1995;
Figure
9.8
). This gene could then only have been expressed if the inserted transposon
were excised by the RAG proteins and the two ends of the exon rejoined and
repaired. The tripartite structure characteristic of the immunoglobulin heavy
chain and T-cell receptor
and
genes could have arisen as a result of the further
insertion of a second RAG transposon into the same exon. Subsequent duplica-
tion of the individual gene segments or of the entire gene would then have served
to generate the 'mammalian-type' or 'cluster-type' organization of mammals and
cartilaginous fishes, respectively (
Figure 9.8
; Litman
et al
., 1993). It therefore
appears likely that our early vertebrate ancestors were successful in taming a
transposon by transforming it into a site-specific recombinase that was then har-
nessed in the cause of generating the genetic diversity so vital for the flexible
adaptive response of our immune system.
and
