Biology Reference
In-Depth Information
enhancer (Jacquemin et al ., 1994). The GH2 locus encodes a protein that differs
from the GH1 -derived growth hormone at 13 amino acid residues. All five genes
share a very similar structure with five exons interrupted at identical positions
by short introns (Hirt et al ., 1987).
On the basis of sequence data, it was initially thought that the evolution of the
GH gene cluster had taken place comparatively recently over the last 15 Myrs by a
process of gene duplication and divergence (Chen et al ., 1989; Miller and
Eberhardt, 1983). The first event is thought to have been the duplication of a sin-
gle ancestral GH gene to generate pre-GH and pre-CSH genes (Barsh et al ., 1983)
followed by the duplication of the newly created gene pair to yield GH1 , CSH1 ,
GH2, and CSH2 ( Figure 4.14 ). Finally, the CSH1 gene was duplicated to form two
genes, one of which ( CSHP1 ) became inactivated through mutation. Although
this sequence of events is probably correct, the estimated timings now appear to be
seriously inaccurate because a GH2 gene has subsequently been reported in
macaque (Golos et al ., 1993). The duplication event creating the GH1 and GH2
genes must therefore have occurred before the divergence of Old World monkeys
and the anthropoid apes ~25 Myrs ago. No study has been performed on either
prosimians or New World monkeys and so the timing of this duplication event
may have to be revised still further as new data emerge. The initially misleading
conclusion as to the timing of the duplication events was probably due to a failure
to consider the effect of gene conversion in minimizing sequence differences
between the different GH loci (Giordano et al ., 1997).
The 70 kb human GH gene cluster contains some 48 Alu sequences (Chen et al .,
1989) some of which may have mediated the unequal recombination events
responsible for the gene duplications (Barsh et al ., 1983). On the other hand, some
Alu sequences have become duplicated along with their associated genes during
the duplication process. One consequence of the relatively recent evolutionary
changes in the GH gene cluster is that multiple sequence homologies and internal
repetitions are still evident within it.
Glycophorin genes. The human glycophorins are encoded by a multigene fam-
ily that has evolved from an ancestral gene that ceased to be functional at some
stage during primate evolution. Glycophorins A and B are the major sialoglyco-
proteins of the human erythrocyte membrane and carry the MN and Ss blood
group antigens respectively. They are encoded by the GYPA and GYPB genes
which occur in a 330 kb cluster together with the glycophorin E ( GYPE ) gene on
chromosome 4q28-q31. This cluster is thought to have arisen by two successive
duplications, the first creating the GYPA gene by duplication of an ancestral gene
(between 9 Myrs and 35 Myrs ago) and the second (5-21 Myrs ago) generating the
GYPB and GYPE genes (Kudo and Fukuda, 1989; Onda and Fukuda, 1995;
Figure 4.15 ). The GYPB gene differs from the GYPA gene by virtue of the pres-
ence of, (i) a G
T transversion at the +1 position of the intron 3 donor splice site
which serves to inactivate the expression of exon III and (ii) a 9 bp insertion at the
5
end of exon V (Blumenfeld et al ., 1997). The GYPE gene differs from the
GYPB gene in that exon IV has been inactivated by a splice site mutation, exon V
contains a 24 bp insertion and the encoded protein has been shortened by 5 amino
acids through the introduction of a premature Stop codon (Blumenfeld et al .,
 
 
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