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Species vary greatly in the degree of clustering, with vertebrates possessing
the most compact and organized Hox clusters. In a few lineages, in contrast,
clusters have become significantly rearranged or dispersed, although inter-
estingly, axially restricted and even collinear expression of at least some Hox
genes is preserved in most cases (reviewed in
Duboule, 2007
).
2.2. Hox-embedded miRNAs
2.2.1.
miR-10
and
miR-933
Several miRNA gene families are embedded inHox clusters (
Fig. 2.1
).
miR-10
is the most ancient and arose early in bilaterian history. Genome searches and
deep sequencing of small RNA libraries have led to identification of
miR-10
sequences in species widely distributed across the bilaterian tree, but not in
cnidarians or poriferans (
Huang
et al
., 2010b
;
Lagos-Quintana
et al
., 2001
;
Lim
et al
., 2003
;
Sperling
et al
., 2009
;
Wheeler
et al
., 2009
).
miR-10
genes show
uncommonly high sequence conservation, with universal conservation of the
5p seed sequence and near-perfect conservation outside the seed region
(although considerable variation is generated via posttranscriptional processing;
see below) (
Ruby
et al
., 2007
;
Wheeler
et al
., 2009
). The genomic position of
miR-10
between
Hox4
and
5
genes is also highly conserved (
Fig. 2.1
).
Whole-cluster duplications in vertebrates increased
miR-10
copy num-
ber, though multiple gene losses also occurred (
Fig. 2.1
). Ancestral gnathos-
tomes likely had three copies on the
Hoxb
-
d
clusters. This condition is
generally preserved except in mammals and birds, in which the
Hoxc
copy
was lost, probably independently given its presence in the squamate
Anolis
carolinensis
(
Amemiya
et al
., 2010
;
Kent, 2002
;
Ravi
et al
., 2009
;
Richardson
et al
., 2007
;
Tanzer
et al
., 2005
). Additional copies of
miR-10
arose via
another round of Hox cluster duplication in teleosts. Fascinatingly, in
zebrafish, the entire
HoxDb
cluster has been reduced to encode only
miR-
10d
(
Woltering and Durston, 2006
). Although the functional significance of
miR-10d
preservation is unknown, it could suggest selection for a particular
miR-10
gene dosage in this lineage.
The genomic position of
miR-10
between
Hox4
and
Hox5
genes is
highly conserved, but there are a few additional exceptions.
miR-10
was
lost or dispersed in lineages where Hox clusters disintegrated, including
Ciona
,
Caenorhabditis elegans,
and
Caenorhabditis briggsae
(
Aboobaker and
Blaxter, 2003
;
Ikuta
et al
., 2004
).
Ceanorhabditis
genomes do, however,
encode a closely related miRNA (
miR-57
), with an identical seed sequence
to
miR-10
(
Lau
et al
., 2001
). Further, some unusual duplications have
occurred.
Amphioxus
was recently shown to have three
mir-10
copies
embedded in its single cluster, one of which is in the conserved position
between
Hox4
and
Hox5
(
Fig. 2.1
;
Campo-Paysaa
et al
., 2011
).
Amphioxus
miR-10
genes are also subject to particularly complex posttranscriptional
regulation, generating at least five mature transcripts (discussed below;
