Biology Reference
In-Depth Information
selection has acted on a genome-wide basis to minimize intron size in this
species. Perhaps the
Fugu
genome has been resistant to colonization by transpos-
able elements and so has no endogenous source of reverse transcriptase to aid the
process of retrotransposition.
Since a high proportion of human genes belong to gene families or super-fami-
lies which have arisen through a process of duplication and divergence (Chapter
4), it is hardly surprising that the locations of introns are often evolutionarily con-
served. Such conservation may be evident in terms of the structures of ortholo-
gous genes, for example the phenylalanine hydroxylase (
PAH
; 12q22-q24) genes
of
Drosophila
and human (Ruiz-Vazquez
et al
., 1996) or the myoglobin gene of the
abalone
Sulculus diversicolor
and the human gene encoding indoleamine 2,3-dioxy-
genase (
IDO
; 8p11-p12; Suzuki
et al
., 1996). It may also be apparent between par-
alogous genes, members of the same gene family within a given species, for
example between the highly homologous human monoamine oxidase A and B
genes (
MAOA
,
MAOB
; Xp11.23; Grimsby
et al
., 1991) or between the human
gene encoding the
-subunit of the granulocyte-macrophage colony stimulating
factor receptor (
CSF2RA
; Xp22.32) and other members of the cytokine receptor
family (Nakagawa
et al
., 1994). However, it is also clear that some evolutionarily
related genes can possess quite divergent intron distributions, for example those
encoding the actin-regulatory proteins, gelsolin (
GSN
; 9q33), the villins (
VIL1
,
2q35-36;
VIL2
, 6q22-q27) and the capping protein Cap G (
CAPG
; 2cen-q24)
(Mishra
et al
., 1994), or the complement proteins
C6
(chromosome 5),
C7
(chro-
mosome 5) and
C9
(5p12-p14) (Hobart
et al
., 1993) or the fibrinogens (
FGA
,
FGB
,
FGG
; 4q31) (Crabtree
et al
., 1985). A particularly dramatic example of post-dupli-
cation structural divergence is provided by the human microfibril-associated gly-
coprotein genes
MFAP2
(1p35-p36) and
MAGP2
(12p12-p13). These two genes
comprise 9 and 10 exons respectively, but sequence and structural conservation as
well as conservation of intron location is confined to exons 8 and 9 of the
MFAP2
gene and exons 7 and 8 of the
MAGP2
gene (Hatzinikolas and Gibson, 1998).
These exons encode the first six of the seven precisely aligned cysteine residues at
the center of both proteins. Divergent exon distribution can arise through intron
insertion and deletion (Section 3.5). Alternatively, it can also arise by recombina-
tion, an example of this is provided by the human prosaposin (
PSAP
; 10q22.1)
gene. The
PSAP
gene is polycistronic, encoding a precursor for four saposins (A,
B, C, and D). Saposins A, B, and D are encoded by three exons, saposin C by only
two. Analysis of intron locations has indicated that the
PSAP
gene evolved by
two duplication events and at least one rearrangement (Rorman
et al
., 1992). This
rearrangement is thought to have involved a double crossover, between the first
and second and between the second and third intron positions of the saposin B
and C coding regions, after the introduction of introns (Rorman
et al
., 1992).
Intron sequences themselves are not usually well conserved during evolution
(Sharp, 1994), a finding which is not surprising in view of the fact that most
intronic sequence is likely to be nonfunctional. However, there are some notable
exceptions: the single intron of the oligodendrocyte-myelin glycoprotein (
OMG
;
17q11-q12) gene exhibits 75% overall homology between human and mouse
(Mikol
et al
., 1993) whilst the 53 introns of the
COL2A1
(12q12-13.2) gene differ
by 69% between the two species (Ala-Kokko
et al
., 1995). Sequences in the third
