Biology Reference
In-Depth Information
Te l
ALB
AFP
AFM
GC
Cen
Gain of 2nd
cleavage in
leader peptide
Loss of
-S-S-
bridge
Loss of exons
2 and 11
Loss of exons
12 and 13
containing -S-S-
bridges 15 - 18
Loss of -S-S-
bridge 1
Ancestral gene
Figure 4.5.
Proposed model for the evolution of the human albumin gene family (after
Nishio
et al
., 1996). Tel: telomere. Cen: centromere. -S-S- : disulfide bridge. The
ALB
and
GC
genes diverged before the emergence of amphibians 400 Myrs ago whilst the
AFP
gene emerged after the separation of amphibians and reptiles some 350 Myrs ago.
apoE
genes have been found in fish, the duplication event from which they both
arose must have occurred before the divergence of tetrapods and teleost fish (Babin
et al
., 1997). The structures of the genes show remarkable similarities: all (with the
exception of
APOA4
) possess four exons with introns interrupting the coding
sequence at very similar locations (
Figure 4.7
). The major difference between the
genes is in the length of the last exon which encodes a variable number of lipid-bind-
ing domains that contain multiple repeats of 22 amino acids each of which represents
a tandem array of two 11-mers (Li
et al
., 1988).
Two of the major known apolipoproteins do not fit easily into the above scheme:
the 29 exon
APOB
(2p24) gene encodes a protein which may be distantly related to
the other apolipoproteins (Li
et al
., 1988) whilst the
APOD
(3q26.2-qter) gene
encodes a protein with a high degree of homology to retinol-binding protein but
little similarity to the other apolipoproteins (Drayna
et al
., 1987).
Complement genes.
The vertebrate complement system may be regarded as a
primitive immune system which lacks the capability to recognize foreign anti-
gens made possible by the evolution of the MHC complex, the T cell receptors
and the immunoglobulins. Gene duplication has played a major role in the evo-
lution of the complement components (Farries and Atkinson, 1991). This is still
evident from the close linkage exhibited by the human complement genes:
C1QA
,
C1QB
,
C1QG
(1p34-p36),
C1S
,
C1R
(12p13), B factor (
BF
),
C2
,
C4A
,
C4B
within the HLA locus at chromosome 6p21,
C6
,
C7
,
C9
(5p13),
C8A
,
C8B
(1p32),
C5
,
C8G
(9q34), membrane cofactor protein (
MCP
), H factor (
HF1
) and
decay accelerating factor (
DAF
) on chromosome 1q32. Some loci however
appear to be isolated, for example I factor (
IF
; 4q25) and
C3
(19p13). Thus,
some complement components exhibit extensive structural homology even
though their genes are not linked (e.g. C3, C4, and C5).
