Biology Reference
In-Depth Information
(e.g. cranial ganglia, teeth and bone) must have required substantial reprogram-
ming of gene networks (Shubin
et al
., 1997). There are several different ways in
which changes in the
HOX
genes have probably influenced morphological evo-
lution: (i) expansion in the structural diversity of
HOX
genes within a given
complex or class (Sharkey
et al
., 1997), (ii) expansion of the number of HOX
complexes (Mayer
et al
., 1998), (iii) the loss of specific
HOX
genes (Aparicio
et
al
., 1997), (iv) changes in the location, timing or level of
HOX
gene expression
(Burke, 1995; Gellon and McGinnis, 1998), and (v) changes in the interactions
between HOX proteins and their target genes, possibly as a result of mutational
changes in
cis
-acting regulatory elements (Carroll, 1995).
Integrin genes.
The integrins are a family of heterodimeric membrane glyco-
proteins that participate in cell adhesion and are involved in a wide range of
cell-cell and cell-matrix interactions. The diversity and specificity of integrin
function is paralleled by the structural diversity potentiated by the existence of
at least 16 different alpha chains and 8 different beta chains. Although, in prin-
ciple, the alpha and beta chains could associate in a multitude of ways, in prac-
tice diversity is limited to certain combinations. These chains are encoded by a
family of genes which are widely dispersed in the human genome (
Table 4.3
).
The alpha chain integrins can themselves be divided into two subgroups by
virtue of the insertion of an I domain of about 180 amino acids in the extracel-
lular region. The I-integrin alpha chain genes (
ITGA1
,
ITGA2
,
ITGAD
,
ITGAM
,
ITGAL,
and
ITGAE
) are thought to have arisen as a result of an early
insertion into a non-I gene followed by gene duplication and divergence. The
clustering of these genes on chromosomes 5 and 16 (
Table 4.3
) is thought to have
resulted from relatively recent gene duplications (Wang
et al
., 1995). The non-I
alpha chain genes (
ITGA2
,
ITGA3
,
ITGA4
,
ITGA5
,
ITGA6
,
ITGA7
,
ITGA8
,
ITGA9
) are largely confined to clusters on chromosomes 2, 12, and 17 (Wang
et
al
., 1995;
Table 4.3
), locations which coincide closely with the homeobox (
HOX
)
gene clusters (see Chapter 2, section 2.1 and chapter 4 section 4.2.1,
G protein
α
subunit genes
). This is suggestive of the occurrence of genomic or chromosomal
duplications involving both types of gene cluster. Some of the beta chain
(
ITGB
) genes are also located on chromosomes 2, 12, and 17 (
Table 4.3
) indicat-
ing common ancestry with the non-I alpha chain genes.
Keratin genes.
The keratins, cytoskeletal proteins of the epithelium, belong to
two families: type I (acidic) and type II (basic) (Fuchs
et al
., 1982). Since keratins
are obligate heteropolymers, keratin intermediate filaments are composed of one
type I and one type II polypeptide. This has led to consistent co-expression of
type I-type II keratin pairs in different types of epithelial cells. The keratins are
evolutionarily related to the family of intermediate filament proteins which
includes vimentin and desmin (Hanukoglu and Fuchs, 1982). Type II keratins
are no more homologous to the type I keratins than they are to other intermedi-
ate proteins (Klinge
et al
., 1987) indicating that the type I and type II keratins
diverged from the common ancestor of all intermediate filaments at about the
same time. This common ancestral gene probably had its origins among the
lower eukaryotes (Fuchs and Marchuk, 1983; Krieg
et al
., 1985). By contrast to
