Biology Reference
In-Depth Information
(Miyabashira
et al
., 1994). Alternatively spliced forms of the nuclear factor I/C
(
NFIC
) and I/X (
NFIX
) genes, linked on human chromosome 19p13.3, are evolu-
tionarily conserved from chickens to humans (Kruse and Sippel, 1994). The
chicken CP49 gene, encoding a 49 kDa cytoskeletal protein, generates two differ-
ent mRNA transcripts, one containing a novel exon encoding 49 amino acids of
helix 1B, the other lacking it (Wallace
et al
., 1998). The transcript containing this
exon is however absent from both the orthologous bovine and human (
BFSP2
;
3q21-q25) genes. Similarly, alternative splicing of the Wilms' tumor (
WT1
;
11p13) gene is evident in various mammals but not in the pufferfish,
Fugu rubripes
(Miles
et al
., 1998). Finally, in the fibronectin (
FN1
; 2q34) gene, where exon EIIIB
is alternatively spliced in a cell-type-specific manner, the pattern of TGCATG
repeats in the downstream intron has been evolutionarily conserved across the
vertebrates suggesting a possible role for these sequences in splice site selection
(Lim and Sharp, 1998).
Alternative processing can however also have had a relatively recent origin.
Insertion of a B2 (SINE) element into the 3
untranslated region of the murine
leukemia inhibitory factor receptor (
lifr
) gene (human equivalent,
LIFR
; 5p12-
p13) encoding the soluble form of the leukemia inhibitory factor receptor (LIFR)
has, by potentiating alternative 3
mRNA processing and alternative splicing,
given rise to a truncated mRNA species (relative to the mRNA encoding the
membrane-anchored LIFR) which encodes soluble LIFR (Michel
et al
., 1997). In
the rat, no such retrotranspositional event has occurred and the soluble form of
LIFR is not found. The potential for alternative processing must therefore have
arisen in the last 20-30 Myrs. Two species of mRNA encoding the metabotropic
glutamate receptor subtype 5 (
GRM5
) gene occur in rat and human which differ
in terms of the presence of a 96 bp insertion thought to result from alternative
mRNA processing (Minakami
et al
., 1993). Another example of the relatively
recent evolution of alternative splicing has been noted in the lecithin: cholesterol
acyltransferase (
LCAT
; 16q22) gene and is present in humans and the great apes
but not in gibbons or Old World and New World monkeys (Miller and Zeller,
1997). Known examples of single base-pair substitutions in splice sites of specific
orthologous gene pairs that are responsible for the evolutionary emergence of
alternative splicing are discussed in Chapter 7, section 7.5.3.
One of the most dramatic inter-specific differences in alternative splicing
involves the human
t
complex responder (
TCP10
; 6q27) gene and its murine
orthologue (Islam
et al
., 1993). The human
TCP10
transcript includes two exons
not present in mouse transcripts, whilst mouse
tcp10
transcripts include up to four
exons that are not present in the human transcript. It is at present unclear whether
a given exon has been incorporated into the transcript of one species or lost from
the other. The recruitment and removal of exons is potentially explicable by single
base-pair substitutions either eliminating splice junctions or converting intronic
DNA sequence into novel splice sites. Islam
et al
. (1993) described this mode of
evolution as 'punctuated equilibrium', a term that is used to refer to evolutionary
situations in which phenotypic characters appear to leap from one equilibrium
state to another in a short space of time. These authors suggested that this mode of
evolution might have been facilitated by the existence of a gene family in which
individual members possessed redundant functions. One family member would
