Biology Reference
In-Depth Information
(e.g. tetrapode/fish) happened more recently than the duplications
which gave rise to RAR
, but that these duplications
occurred after the speciation between
Ciona
and vertebrates. Thus, these
duplications date to the origin of vertebrates. If we go back in time
before the split between the
Ciona
and vertebrate RAR orthologs, we do
not find a speciation node, but an older gene duplication that gave rise
to RARs and other nuclear receptors. When did this older duplication
occur? The ROR/HR3 subtree includes not only speciations among
chordates and vertebrate-specific duplications, like RARs, but also a
speciation node between chordates on the one hand and insects and
nematodes on the other — the speciation between ecdysozoans and
deuterostomes that occurred at the origin of bilaterian animals.
45,46
In the
tree, this speciation is clearly more recent than the duplication leading to
RARs, RORs, and other nuclear receptors. We can therefore assume the
following order of events (Fig. 1): duplications leading to proto-RAR,
proto-ROR, proto-Rev-erb, and other NRs, followed by speciation
between ecdysozoans and deuterostomes. Then, to explain the lack of
any RAR orthologs in the sequenced ecdysozoan genomes, we must infer
that this gene was lost in ecdysozoans, and that RAR does not appear as
a vertebrate innovation but rather as an ecdysozoan loss. Of note, an
RAR ortholog has also been identified in the sea urchin genome,
47
a deuterostome but not a chordate.
In the analysis of the whole superfamily, we find a recurrent pattern:
vertebrate innovations are invertebrate losses.
44
Symmetrically, insect-
specific genes (e.g. E78) are ancestral bilaterian genes lost in the chor-
date lineage. This pattern has been spectacularly confirmed for steroid
receptors, with the cloning and characterization of an estrogen receptor
ortholog from a mollusk.
48,49
Indeed, ancestral sequence reconstruction
shows that the ancestor of bilaterian animals probably had a receptor acti-
vated by estrogen.
α
, RAR
β,
and RAR
γ
2.2.2. Why do humans have three retinoic acid receptors?
Flies may not have retinoic acid receptors, but humans have three.
RAR
are paralogs, kept from the genome duplica-
tions at the origin of vertebrates. All three bind all-trans retinoic acid,
α
, RAR
β,
and RAR
γ
