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Ancient origin of the Hox gene cluster

The Hox gene cluster has a crucial function in body patterning during animal development. How and when this gene cluster originated is being clarified by recent data from Cnidaria, a basal animal phylum. The characterization of Hox-like genes from Hydra, sea anemones and jellyfish has revealed that a Hox gene cluster is extremely ancient, having originated even before the divergence of these basal animals.

Key Points

  • The Hox genes are a cluster of homeobox-containing genes that are required to pattern the principal axis of the animal body.

  • The ParaHox gene cluster consists of genes that are related to those in the Hox cluster. Both Hox and ParaHox genes are thought to have arisen by duplication and divergence from a more ancient `ProtoHox' cluster that was present in an ancestral animal.

  • Recent data from Cnidaria, (jellyfish, sea anemones, Hydra) have had an important impact on our understanding of the evolution of the Hox gene cluster.

  • It was originally thought that the cnidarian Hox genes were closer to the hypothetical ProtoHox cluster.

  • Recent sequence analyses indicates that cnidarians may possess true homologues of the Hox and ParaHox genes and that Hox-like genes are arranged in clusters in the genome of a sea anemone (a cnidarian).

  • The duplication of the ProtoHox cluster into a Hox gene cluster and ParaHox genes preceded the cnidarian–bilaterian divergence.

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Figure 1: Cnidaria.
Figure 2: Metazoan tree.
Figure 3: Hox/ParaHox gene cluster evolution.

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Acknowledgements

We are grateful to B. Galliot, D. Miller, V. Schmid, J. Spring and J. Finnerty for communication of results before publication, and to F. Mazet for discussion. The authors' work is funded by the BBSRC.

Author information

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Supplementary information

Figure 1. Cnidarian Hox-like homeodomain sequences

Figure 2. Alignment of the HEP motif at the 5' end of Cnox2 proteins, with triploblast Gsx proteins and Hox proteins with the most similarity to this domain. (PDF 94 kb)

Related links

Related links

DATABASE LINKS

Amphioxus

FURTHER INFORMATION

An introduction to cnidarian phylogeny and classification

A useful list of cnidarian links and resources on Dr R. Steele's homepage

ENCYCLOPEDIA OF LIFE SCIENCES

Evolutionary developmental biology: Hox gene evolution

Glossary

BILATERIAN

An animal that shows bilateral symmetry across a body axis. Bilaterians include chordates, arthropods, nematodes, annelids, molluscs and others. Echinoderms are included in Bilateria, even though their adults show pentaradial symmetry, because they evolved from bilateral ancestors and their larvae have bilateral symmetry. All living bilaterians are also `triploblasts'.

BASAL

An evolutionary lineage, or animal within a lineage, that arises close to the root or base within a phylogeny.

DIPLOBLAST

An animal with only two germ layers (ectoderm and endoderm), including the Cnidaria, Ctenophora and, according to some authors, Placozoa and Porifera.

TRIPLOBLAST

An animal with three germ layers (ectoderm, mesoderm and endoderm).

DERIVED

Evolved to a state that is not like the primitive condition.

CHORDATE

A phylum of animals characterized by possession of a notochord (and post-anal tail, somites/myotomes and gill slits). It includes the urochordates (such as ascidians), cephalochordates (amphioxus) and vertebrates.

AMPHIOXUS (literally, sharp at both ends.)

The common name for the cephalochordate Branchiostoma, which is the closest living invertebrate relative of the vertebrates.

PROTOHOX

Hypothetical homeobox gene cluster that duplicated to produce the Hox and ParaHox gene clusters.

NEIGHBOUR-JOINING

A distance-based molecular phylogenetic method involving sequential addition of taxa and minimization of branch lengths that does not assume a molecular clock.

DEUTEROSTOME

A bilaterian animal whose mouth forms as a secondary opening, separate from the blastopore. Deuterostomes include chordates, hemichordates and echinoderms.

PROTOSTOME

A bilaterian animal whose mouth and anus develop from the same invagination (the blastopore) during embryogenesis

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Ferrier, D., Holland, P. Ancient origin of the Hox gene cluster. Nat Rev Genet 2, 33–38 (2001). https://doi.org/10.1038/35047605

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