Biology Reference
In-Depth Information
Several possible relationships may exist between the structural domains and
the arrangement of exons in the gene (
Figure 3.4
). In many genes encoding globu-
lar proteins (e.g. the globins), the exons correspond closely to the structural
domains thereby ensuring that when exon duplication has occurred, it has given
rise to domain duplication (Li, 1997). In the majority of cases, however, a more
complex relationship exists between domains and exons (Li, 1997). Thus it may
be that the correspondence between exons and domains is only approximate. In
some cases, an exon may encode two or more domains whilst in others, a single
domain may be encoded by two or more exons. Finally, there may be no obvious
correspondence between exons and domains.
Taking together the results of all the studies so far performed, the introns-
early and introns-late viewpoints can to some extent be reconciled once we
accept that they are not necessarily mutually exclusive, even for a single specific
gene. A relationship between exon distribution and the domain structure of the
encoded protein may therefore exist for some genes or some introns/domains
within the same gene/protein. For others, it may be that such a relationship did
once exist but has decayed with the passage of evolutionary time (Traut, 1988).
Similarly with intron location, some introns were already present in primordial
genes, whereas other genes lost or more likely gained (Cho and Doolittle, 1997)
their introns at later stages of evolution. De Souza
et al
. (1998) have suggested
(a)
DNA sequence around intron 8 of the histidyl-tRNA synthetase (HARS) gene
HARS-Fugu
HARS
-Hamster
HARS
-Human
TATGTTGGTATGCAAG
gtgag
attt---tctgtagGTGGAATGGATTTGGCTGAACGT
TATGTCCAGCAGCACG
GTGAG
gtaaa-----gctccccagGTGTGTCTGGTAGAGCAG
TATGTCCAGCAACATG
GTGGG
GTATCCCTGGTGGAACAG
(b)
Model for the shift of intron 8
Ta k i n g t h e
Fugu
intron as the ancestral one, an A to G change (arrowed) creates a cryptic splice site
↓
Y V G M Q G G M D L A E R
TATGTTGGTATGCAAGgtgag
a
ttt---tctgtagGTGGAATGGATTTGGCTGAACGT
TATGTTGGTATGCAAGgtgag
g
ttt---tctgtagGTGGAATGGATTTGGCTGAACGT
An additional insertion of a G (arrowed) then creates a frameshift (top) which would normally be lethal
but is rescued by the cryptic splice site becoming functional (bottom)
↓
Y V G M Q G G D G F G STOP
TATGTTGGTATGCAAGgtgag
g
ttt---tctgtagGTGGA
G
ATGGATTTGGCTGAACGT
TATGTTGGTATGCAAGGTGAG
g
ttt---tctgtaggtgga
g
ATGGATTTGGCTGAACGT
Y V G M Q G E M D L A E R
The result is a 5 nucleotide shift in the position of the intron but only a G to E substitution in the
amino acid sequence
Old Y V G M Q G
G
M D L A E R
New Y V G M Q G
E
M D L A E R
Figure 3.3.
Intron sliding in the histidyl-tRNA synthetase (
HARS
) gene (after Brenner
and Corrochano, 1996). (a) Comparison of the sequence around intron 8 in pufferfish
(
Fugu
), human and hamster
HARS
genes. Lower case letters denote intron sequence,
upper case letters exon sequence. The segment of the
Fugu
intron identical to hamster
exon sequence is given in bold type. (b) Model for the sliding of intron 8. Nucleotide
changes are in bold type and marked by arrows.
