Biology Reference
In-Depth Information
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Figure 8.11. A possible scheme for the evolution of the human transferrin ( TF ) gene
(after Park et al ., 1985). The ancestor of the transferrin gene was duplicated by an
intragenic crossing over event (A) generating an internally duplicated gene which had
lost one of its leader peptide coding exons and one of its terminal 3 exons (B). During
evolution, exon 4 (short arrow) was deleted. In C, the upper numbers correspond to the
exon numbering in A and B whilst the lower ones correspond to the exons of the extant
human transferrin gene.
internal duplication probably also occurred in the cystic fibrosis transmembrane
conductance regulator ( CFTR ; 7q31.3) gene which encodes a protein with two
transmembrane domains and two nucleotide binding fold domains (Hughes 1994).
By contrast, successive duplications of ancestral domains appear to have occurred
in the human kininogen ( KNG ; 3q27) gene (Kellermann et al ., 1986). Other exam-
ples of human proteins displaying internal domain duplication include calbindin
(six 43 amino acid repeats), fibronectin (twelve 40 amino acid repeats), plasmino-
gen (five 79 amino acid repeats) and
-tropomyosin (seven 42 amino acid repeats)
(Li 1997). Many other genes are also likely to have evolved by internal gene dupli-
cation but the duplicated regions have probably diverged so much over evolution-
ary time that sequence homology between them is no longer discernible.
8.6.2 Exon duplication
It has been estimated that at least 6% of exons in human genes have arisen by the
duplication of pre-existing exons (Fedorov et al ., 1998). One example is that of the
human CHC1 (1p36.1) gene, which encodes a protein involved in the coupling
between DNA replication and mitosis. This gene comprises 14 exons, eight of
which encode the 7 tandemly repeated domains of ~60 amino acids within the
CHC1 protein; each repeat is encoded by a single exon except for repeat IV which
is encoded by exons 10 and 11 separated by an inserted intron (Furuno et al ., 1991;
Figure 8.12 ). The CHC1 gene therefore appears to have arisen through the ampli-
fication of a primordial exon (Furuno et al ., 1991). Gene construction by exon
amplification has also been employed in the macrophage mannose receptor
( MRC1 ; 10p13; Kim et al ., 1992) gene; 26 of the 30 exons of the MRC1 gene serve
to encode the eight C-type carbohydrate recognition domains. Ceruloplasmin
 
 
 
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