Biology Reference
In-Depth Information
almost certainly an adaptive response to the wide range of novel pathogens that
challenged early tetrapods in their new terrestrial environment.
The evolution of the immunoglobulin genes is subject to at least two distinct
types of constraint: existing gene segments must be conserved in order to meet
recurring immunological challenges but diversity must be continually created to
meet new immunological challenges. The duplication of gene segments provides
a means to achieve this by ensuring that old structures/functions are maintained
at the same time as new ones are being created.
T-cell receptor genes.
The T-cell receptor plays an important role in antigen
recognition during the immune response. The four T-cell receptor chains (
,
,
,
and
), members of the immunoglobulin superfamily, dimerize to form two types
of receptor (
). In the human genome, these chains are encoded by four
genes:
TCRA
and
TCRD
(14q11.2),
TCRB
(7q35), and
TCRG
(7p14-p15). The
location of the
TCRD
gene is highly unusual in that it lies within the
TCRA
gene:
the multiple gene units are organized as V
/
,
/
(Hockett
et al.
,
1988). Each locus comprises a large number of tandemly arrayed variable (V)
genes, diversity (D) segments (
TCRB
and
TCRD
), a number of clustered joining
(J) elements and one or two constant (C) region genes. These gene segments
undergo somatic rearrangement during lymphocyte differentiation to yield either
V/J or V/D/J genes. As with the immunoglobulin genes (Section 4.2.4,
Immunoglobin genes
), the origin of the T-cell receptor genes probably occurred very
early in the evolution of the jawed vertebrates (Rast
et al
., 1997). The tandem
arrays of V genes seen in extant vertebrate genomes have arisen subsequently by
serial duplication, generating the sizeable repertoire of T-cell receptor V genes
essential for creating diversity of antigen recognition specificity.
The
TCRB
gene has been the best characterized of the four loci with the
sequencing of 685 kb from the region (Rowen
et al
., 1996). This region contains 46
variable gene segments, 19 pseudogenes and two clusters of D, J, and C segments.
A further 22 additional sequences, termed 'relics' by the authors, were also iden-
tified. These sequences exhibited limited homology to V gene segments and rep-
resent partial pseudogenes extensively altered by insertions and deletions. Some
30% of the
TCRB
locus is composed of genome-wide interspersed repeats but
these sequences do not appear to have facilitated the duplication of locus-specific
repeats. Some of these repeats within the
TCRB
locus have been shown to harbor
trypsinogen genes (
PRSS1
,
PRSS2
). These genes must have been conserved for
at least 350 Myrs because a trypsinogen gene cluster is present at this location in
both mouse and chicken. Higher primates contain similar numbers of V gene seg-
ments at the
TCRB
locus: human (47), gorilla (45), orangutan (57), macaque (57)
with the greater number of V genes in orangutan and macaques being due to
amplification of the TCRBV7, 9 and 23 subfamilies (Charmley
et al
., 1995).
-V
-D
-J
-C
-J
-C
4.3 Convergent evolution
Most members of the gene and protein families discussed in Section 4.2 have been
subject to
divergent evolution
, the process by which homologous proteins or
