Biology Reference
In-Depth Information
by single base-pair substitutions and micro-deletions and insertions to perform
a role in lens-specific expression (Gonzalez
et al
., 1995). By contrast, in birds,
recruitment of the
-crystallins appears to have come about through
the modification of pre-existing promoters utilized for nonlens tissue expression
(Hodin and Wistow, 1993).
1-,
2- and
Collagen genes.
The collagens are multi-domain proteins which serve as
structural molecules of the extracellular matrix. They have a very ancient origin
as evidenced by their presence in sea urchins, annelids,
Drosophila
and even jel-
lyfish and sponges (Exposito and Garrone, 1990; Exposito
et al
., 1991; reviewed
by Garrone, 1998). These proteins contain one or more domains with a triple
helical conformation characterised by a repeating Gly-X-Y amino acid motif.
A total of 19 types of collagen (I to XIX) have so far been defined in humans; these
comprise homo- or heteromeric assemblies of specific polypeptide chains (
Table 4.2
).
A minimum of 34 genes on 13 different human chromosomes are required to encode
these chains (
Table 4.2
). Based on their structures, the collagens may be divided into
several distinct classes: fibrillar (I, II, III, V, XI), basement membrane (IV), fibril-
associated with interrupted triple helices (IX, XII, XIV, XIX), filament-producing
(VI), network forming (VIII, X) and anchoring fibril (VII). The class structure of the
proteins and the homologies between the members of each class is reflected in the
evolutionary relationships between the genes that encode them, their structure and
often their chromosomal location (reviewed by Prockop and Kivirikko, 1995; van
der Rest and Garrone, 1991; Vuorio and de Crombrugghe, 1990).
The fibrillar collagens are proteins with a continuous triple helical domain
containing uninterrupted Gly-X-Y motifs. Their genes are thought to have
diverged some 800-900 Myrs ago (Runnegar 1985) but still share a very similar
exon-intron organization comprising 52-54 exons of which 42 have specific
lengths: 45 bp, 54 bp, 99 bp, 108 bp, and 162 bp representing multiples of the 9 bp
encoding the Gly-X-Y motif. The latter three lengths are combinations of the first
two suggesting that they may have been derived from an ancestral 54 bp exon by
duplication and recombination events (
Figure 4.8
). These events may have been
mediated by recombination between introns (Butticé
et al
., 1990; Chu
et al
., 1984;
Yamada
et al
., 1980). Partial gene duplication events are unlikely to have disrupted
gene function because multiples of 9 bp would not have altered the reading frame
of the proteins. The 66 exon
COL5A1
and
COL11A2
genes appear to have
increased in size through an increase in the number of 54 bp exons (Takahara
et
al
., 1995; Vuoristo
et al
., 1995). The
COL3A1
and
COL5A2
genes are both located
at chromosome 2q31, indicative of a close evolutionary relationship.
Although the genes encoding the basement membrane collagens possess 46-52
exons, they differ from the fibrillar collagen genes in that they possess many fewer
exons of length 45 bp and 54 bp. Further, the exons vary widely in size, do not
always begin with a Gly codon and often split codons. Their similar exon-intron
organization testifies however to a common evolutionary origin. Moreover, the six
type IV genes are arranged in syntenic pairs [
COL4A1
and
COL4A2
(13q34),
COL4A3
and
COL4A4
(2q36-q37),
COL4A5
and
COL4A6
(Xq22)] with head-to-
head arrangement (sometimes sharing promoter elements), consistent with a
model of gene duplication and divergence.
