Biology Reference
In-Depth Information
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Figure 3.6.
Different stages in the conversion of a domain to a module (redrawn from
Patthy 1994). The boxes represent exons separated by introns. The exon encoding the
signal peptide is solid whilst the exons encoding the protein fold (A) are lightly shaded.
Stage 1: Insertion of introns of identical phase at amino and carboxy terminal boundaries
of protein fold. Stage 2: Tandem duplications of symmetrical protomodule A via intronic
recombination. Stage 3: Module A is transferred to a new location.
LDL receptor, EGF, and C7 modules through multiple occurrences of intron
insertion and removal. Finally, the exon shuffling rules do not apply in some
cases of genes encoding proteins common to both prokaryotes and eukaryotes
(phosphoglycerate kinase, alcohol dehydrogenase, pyruvate kinase, glyceralde-
hyde-3-phosphate dehydrogenase, triosephosphate isomerase and dihydrofo-
latereductase). This is consistent with the view that these evolutionarily very
ancient genes did not evolve by exon shuffling (Patthy, 1987, 1991a). However,
Long
et al
. (1995) claimed that there is an excess of symmetrical exons in the
ancient conserved regions of eukaryotic genes (regions homologous to prokary-
otic genes), a finding that is consistent with at least some introns being of
ancient origin (Gilbert
et al
., 1997).
3.6.3 The serine proteases of coagulation
One of the archetypal examples of the evolution of modular proteins by exon shuf-
fling is that of the serine proteases of coagulation. As the completed primary
sequences of hemostatic factors became available, it was noticed that certain
domains of shared homology recurred many times in diverse proteins.
Figure 3.7
depicts 11 proteins of coagulation and fibrinolysis in such a way as to emphasise
their modular composition. The kringle domain is present in prothrombin as well
as three proteins of fibrinolysis (tPA, urokinase and plasminogen) and may play a
role in fibrin binding. A trypsin-like serine protease domain is common to all the
