Biology Reference
In-Depth Information
with the target genes and analyze their phylogeny, in some cases we per-
form the reverse. For this, we rely on existing databases of gene trees,
such as TreeFam
37
or the databases of the Pôle Bioinformatique Lyonnais
(PBIL),
38-40
combined with tree reconciliation tools.
41
The latter allow us
to specify a topology and search for all gene trees (or subtrees) that
match it. In this way, we can identify all genes that were retained in dupli-
cate after whole-genome duplication in fish, but not duplicated in
tetrapodes, specifying also species or lineages in which gene loss is
allowed or forbidden.
2.2. The Importance of Duplication and Loss
2.2.1. Why don't flies have retinoic acid receptors?
Nuclear hormone receptors (or nuclear receptors, NRs) are transcription
factors that are specific to Metazoa (animals). They include receptors of
major hormones, such as steroids or thyroid hormones. NRs play impor-
tant roles in many central biological processes, notably development
(reviewed in Laudet and Gronemeyer
42
). A typical example is the group
of retinoic acid receptors (RARs), which includes RAR
α
, RAR
β,
and
RAR
in humans. RARs mediate the regulation of anteroposterior
expression of Hox genes in vertebrate development by retinoic acid.
Whereas the Hox genes are largely conserved between mammals and
flies, no ortholog of RAR is found in the
Drosophila
genome, and neither
are present orthologs of classical steroid receptors (ER, AR, PR, MR, and
GR) nor of thyroid hormone receptors (TRs). Moreover, orthologs of
these genes are not found in nematode genomes either. The steroid
receptors are even absent from the genome of the sea squirt,
Ciona
intestinalis
. In fact, while most of the 48 human nuclear receptors have
known ligands (hormones or fatty acids), most of the 21 fly nuclear
receptors are so-called “orphans”, without a known ligand. These obser-
vations led to the suggestion that most liganded nuclear receptors were
vertebrate innovations.
9,43
When a sufficient sampling of animal genomes became available, we
took advantage of the conserved structure of nuclear receptors to search
for all homologs, and performed a global phylogenetic analysis of the
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