Biology Reference
In-Depth Information
expressing a given OR gene are located in the same zone but in that zone they are
interspersed with neurons expressing other ORs (Sullivan
et al
., 1996). However,
OR genes expressed in the same zone map to numerous different loci whereas a
single OR locus may contain genes expressed in different zones (Sullivan
et al
.,
1996). Since some of the OR pseudogenes have been found to be expressed, it is
possible that some of those neurons that only express a single receptor type may
be nonfunctional (Crowe
et al
., 1996).
The origin and emergence of the olfactory receptor gene family probably pre-
ceded the divergence of the mammals (Ben-Arie
et al
., 1993; Issel-Tarver and
Rine, 1997). In the primates, the olfactory receptor genes appear to have been in a
considerable state of flux with numerous translocations, duplications and dele-
tions occurring during the evolution of the great apes (Trask
et al
., 1998). The ori-
gin of ORs is unclear but their expression during spermatogenesis and their
presence in mature sperm cells suggests that their original function could have
been in sperm physiology (Vanderhaeghen
et al
., 1997a, 1997b).
4.2.4 Genes which undergo programmed rearrangement
The immunoglobulin and T-cell receptor genes are members of the immunoglob-
ulin superfamily and share the common property of being assembled from multi-
ple gene coding segments in the lymphocyte. In the germline, the genes encoding
the variable portions of these receptors are usually split into variable (V), J (join-
ing) and D (diversity) segments that are joined together by a somatic process of
site-specific recombination that involves the recombination-activating proteins
RAG1 and RAG2 (see Chapter 9, section 9.4.2) to generate exons that encode the
antigen-binding portion of the polypeptide.
Immunoglobulin genes.
A diverse repertoire of human antibodies is generated
by the combinatorial somatic rearrangement of a relatively small number of gene
segments, variable (V
H
), diversity (D) and joining (J
H
) segments for the heavy
chain V region, and variable (V
L
) and joining (J
L
) segments for the light chain V
region. The J
H
and J
L
segments are spliced to the constant region genes of the
heavy (C
H
) and light (C
L
) chains following mRNA transcription.
The human immunoglobulin genes are mainly distributed between three chro-
mosomal locations: 14q32 for the heavy chain loci, 2p12 for the
light chain loci
and 22q11 for the
light chain loci. The 1100 kb human heavy chain locus con-
tains 51 functional V
H
gene (
IGHV
) segments, ~30 D segments (
IGHDY
), 6 func-
tional J
H
segments (
IGHJ
) and 9 functional C
H
genes:
ยต
(
IGHM
),
(
IGHD
),
3
(
IGHG3
),
2
(
IGHA2
) (
Figure 4.29
; Cook and Tomlinson, 1995). The human C
H
gene locus
clearly exhibits dyadic symmetry as a result of a duplication event that included
the C
1 (
IGHG1
),
1 (
IGHA1
),
2 (
IGHG2
),
4 (
IGHG4
),
1 (
IGHE
) and
gene cluster in the ancestor of the great apes (Kawamura and
Ueda, 1992). The symmetry is imperfect in extant species because the C
-C
-C
-C
gene was
lost through independent deletion events in humans, chimpanzees, gorilla and
the white-handed gibbon (
Hylobates lar
) whereas in the orangutan, the C
gene
was deleted as well as the C
gene (Kawamura and Ueda, 1992).
