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domains (“posterior prevalence”;
Duboule & Morata, 1994
). The initial
transcriptional activation of
Hox
genes requires general cell signaling path-
ways (e.g., Wnt, Notch, FGF; reviewed in
Deschamps & van Nes, 2005
), as
well as the combined readout of regulatory elements (e.g., in
Drosophila
:
Maeda &Karch, 2006, 2010
). Segmental identity is subsequently maintained
by fixing these expression patterns. This mechanism seems to be particularly
stable, as illustrated by adult human cell lines derived from different body
levels, which continue to transcribe
Hox
combinations resembling, to some
extent, their embryonic body levels of origin (
Chang et al., 2002; Rinn,
Bondre, Gladstone, Brown, & Chang, 2006
).
In bilateria,
Hox
genes are often linked in a genomic cluster and the ever
increasing availability of novel animal genomes suggests that early bilaterian
animals carried an ancestral
Hox
cluster that contained a rather small number
of genes (
Chourrout et al., 2006
). Horizontal gene duplication and subse-
quent reorganization gave rise to a more complex cluster (
Fig. 4.2
), which
may have permitted the evolution of the wide diversity in bilaterian body
plans.
Drosophila
subspecies contain eight
Hox
genes, localized in two to
three split segments of an ancestral cluster (see
Akam, 1989; Negre,
Ranz, Casals, Caceres, & Ruiz, 2003; Ranz, Segarra, & Ruiz, 1997
). On
the other hand, the primitive chordate Amphioxus has a much-expanded
Hox
cluster that contains 15 genes, each being somewhat orthologous to
either one of the
Drosophila Hox
genes (
Fig. 4.2
;
Holland, Albalat, et al.,
2008
). In vertebrates, multiple rounds of genome duplications, which
occurred at the basis of this taxon (
Ohno, 1970
), generated four paralogous
Hox
clusters (and more in most fish species; see
Kuraku & Meyer, 2009
),
which are structurally related to that of Amphioxus (
Lynch & Wagner,
2009; Ohno, 1970
). Within the vertebrate gene clusters, the high functional
equivalence of the HOX proteins (e.g.,
Greer, Puetz, Thomas, & Capecchi,
2000
) may have allowed for substantial structural reorganization and fine
tuning of the transcriptional regulatory programs.
Notwithstanding the common themes in
Hox
gene organization, the
genomic aspects of
Hox
clusters can vary considerably between animals
(
Fig. 4.3
;
Duboule, 2007
). For example, mammalian
Hox
clusters display
the strictest internal organization: (1)
Hox
genes are present in uninterrupted
and compact genomic clusters, (2) they are all transcribed in the same ori-
entation, (3) they contain few and short introns, and (4) they are generally
depleted from repetitive elements (
Fried, Prohaska, & Stadler, 2004
). In
Amphioxus, as well as in many invertebrates, a single cluster exists that is
similarly organized, yet with a less stringent structure. As a result, the gene
