Biology Reference
In-Depth Information
interferon-
gene (
IFNB1
) at 9p21
(Diaz
et al
., 1994), the heat shock 70 kDa protein genes (
HSPA2
, 14q22-q24;
HSPA1A
, 6p21.3; Milner and Campbell 1990), the pyruvate dehydrogenase E1
(
IFNA
) gene cluster and the interferon-
α
subunit (
PDHA1
; Xp22) gene (Dahl
et al
., 1990), the formyl peptide receptor
(
FPR1
; chromosome 19) gene (De Nardin
et al
., 1992), the serotonin receptor
genes
HTR1D
(1p34.3-p36.3) and
HTR1F
(Demchyshyn
et al
., 1992; Adham
et
al
., 1993), the casein kinase 2-
1 subunit (
CSNK2A1
; 20p13) gene (Devilat and
Carvallo, 1993), the
ID2
gene (2p25) encoding an inhibitor of DNA binding
(Kurabayashi
et al
., 1993), the purinergic receptor (
P2RY1
; chromosome 3) gene
(Ayyanathan
et al
., 1996) and the calmodulin-like genes (
CALML3
, 10p13-pter;
CALML1
, 7p13-pter; Berchtold
et al
., 1993; Koller and Strehler, 1993).
Intriguingly, >90% of the human genes that encode the G-protein-coupled recep-
tor family are intronless, a finding which may reflect a retrotranspositional origin
prior to gene duplication (Gentles and Karlin, 1999).
Introns in human genes vary enormously in size, from as little as 24 bp in the
case of the parvalbumin (
PVALB
; 22q12-q13) gene, to in excess of 600 kb in the
case of the
1(V) collagen (
COL5A1
; 9q34.2-q34.3) gene (Takahara
et al
., 1995).
Minimum intron size may be determined by the need to prevent steric hindrance
between splicing factors. Intron size is not usually well conserved between orthol-
ogous genes. Thus during the evolution of the higher primates, intron 8 of the
lamin B (
LMNB2
; 19p13.3) gene increased very dramatically in size as a result of
a repeat expansion (de Stanchina
et al
., 1997), whilst intron 6 of the Ewing sar-
coma breakpoint region 1 (
EWSR1
; 22q12) gene expanded progressively through
successive retrotransposition and recombination events involving
Alu
sequences
(Zucman-Rossi
et al
., 1997). Similarly, the paralogous murine phospholipase D1
and D2 genes differ in size as a result of a 20-fold expansion/contraction of intron
size in one of the genes (Redina and Frohman, 1998). There are, however, notable
exceptions to the rule of lack of conservation; for example, the sizes of the 53
introns of the human and mouse
1(II) collagen (
COL2A1
; 12q12-q13.2) genes
differ on average by only 13% (Ala-Kokko
et al
., 1995).
In the context of intron size, one enigma is the pufferfish (
Fugu rubripes
) whose
400 Mb genome is 1/7 the size of the human genome, is relatively devoid of repet-
itive DNA, and contains comparatively short introns (75% are less than 120 bp in
length) (Brenner
et al
., 1993). A dramatic example of the economy manifested by
the
Fugu
genome is provided by the relative size of intron 7 of the Duchenne
muscular dystrophy (
DMD
; Xp21) gene in
Fugu
(2.4 kb) as compared to its
human counterpart (109.6 kb) (McNaughton
et al
., 1997). At least 40% of the
human intron is made up of LINE elements,
Alu
sequences, THE-1 and related
LTR sequences, interspersed repeat sequences, a
mariner
transposon and other
repeats including microsatellites whose insertion served to double the size of the
intron over the last 130 Myrs (McNaughton
et al
., 1997). This example is not
unrepresentative of the size differences noted between orthologous human and
Fugu
introns; thus the neurofibromatosis type 1 (
NF1
; 17q11) gene spans only 27
kb in
Fugu
as compared to 335 kb in human (Kehrer-Sawatzki
et al
., 1998).
Whether or not the size of the
Fugu
genome represents the ancestral state of the
early vertebrate genome is unclear but its size may well approach the minimum
sustainable for a vertebrate. We can only speculate as to the possible reasons why
