Introns, exons, and evolution - Human Gene Evolution - page 121

lipoprotein lipase ( LPL ; 8p22), hepatic lipase ( LIPC ; 15q21-q23) and pancreatic
lipase ( PNLIP ; 10q24-p26) genes and the homologous yolk protein 1 gene from
Drosophila ( Figure 3.5 ; Kirchgessner et al ., 1989). Another example is provided by
the human thyroid peroxidase ( TPO ; 2pter-p24) and myeloperoxidase ( MPO ;
17q21.3-q23) genes (Kimura et al ., 1989).
The mammalian hepatocyte nuclear factor 1 ; TCF1 ; 12q24.3) gene

possesses nine exons, whereas its avian and amphibian counterparts have ten
(Hörlein et al ., 1993). This difference is explicable in terms of the loss in mammals
of intron 9 which in the chicken gene sub-divides the serine-rich transactivation
domain. Interestingly, there is a sequence at the 3

(HNF

end of intron 9 in the chicken
gene which matches a conserved element used as a joining signal in immunoglob-
ulin and T-cell receptor genes. Similarly, a perfectly conserved heptamer
(CACAGTG) box, a recombination signal sequence in immunoglobulin genes, is
found at the junction of the fused exon 9-exon 10 in the rat HNF

gene. Hörlein
et al . (1993) speculated that V(D)J recombinase may have been involved in the
excision of intron 9 in the mammalian gene.
The human surfeit 5 ( SURF5 ; 9q34.1) gene contains an intron in its 5

untranslated region which is not present in the mouse or rat Surf5 genes (Duhig
et al ., 1998). This additional intron is also present in apes, Old and New World
monkeys and the prosimian Galago . Duhig et al . (1998) speculated that the
intron was introduced after the divergence of primates and rodents but before
the divergence of the human and prosimian lineages.
A considerable number of examples are therefore now known of introns
which have been either gained or lost during evolution as a result of the action
of several distinct mechanisms. Such examples are certainly supportive of the
introns-late theory.

3.6 Exon shuffling

3.6.1 Exon shuffling in the evolution of human genes

Exon shuffling may be defined as the transfer of exons, encoding specific functional
modules, between genes so that the module-associated functions are conferred upon

PRIMORDIAL GENE
(14 introns)

Figure 3.5. A model for the
evolution of the lipase gene
family. The six known members
of this family (lipoprotein lipase
(LPL), hepatic lipase (HL),
pancreatic lipase (PL) and the
Drosophila yolk proteins (YPs))
evolved from an ancestral gene
containing 14 introns by a
series of gene duplications, exon
shuffling events together with
the gain and loss of introns
(after Kirchgessner et al., 1989).

Gene duplication

Ty r s u l f a t i o n
Exon addition
Loss of introns
1, 3 - 11
Loss of two
terminal exons

Loss of introns
1, 3, 5, 8, 10

Loss of introns
4 and 14

Gene duplication Gene duplication

LPL HL PL YPs 1, 2 and 3