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doi: 10.1186/gb-2003-4-2-r12. Epub 2003 Jan 23.

Genesis and evolution of the Evx and Mox genes and the extended Hox and ParaHox gene clusters

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Genesis and evolution of the Evx and Mox genes and the extended Hox and ParaHox gene clusters

Carolina Minguillón et al. Genome Biol.2003.

Abstract

Background: Hox and ParaHox gene clusters are thought to have resulted from the duplication of a ProtoHox gene cluster early in metazoan evolution. However, the origin and evolution of the other genes belonging to the extended Hox group of homeobox-containing genes, that is, Mox and Evx, remains obscure. We constructed phylogenetic trees with mouse, amphioxus and Drosophila extended Hox and other related Antennapedia-type homeobox gene sequences and analyzed the linkage data available for such genes.

Results: We claim that neither Mox nor Evx is a Hox or ParaHox gene. We propose a scenario that reconciles phylogeny with linkage data, in which an Evx/Mox ancestor gene linked to a ProtoHox cluster was involved in a segmental tandem duplication event that generated an array of all Hox-like genes, referred to as the 'coupled' cluster. A chromosomal breakage within this cluster explains the current composition of the extended Hox cluster (with Evx, Hox and Mox genes) and the ParaHox cluster.

Conclusions: Most studies dealing with the origin and evolution of Hox and ParaHox clusters have not included the Hox-related genes Mox and Evx. Our phylogenetic analyses and the available linkage data in mammalian genomes support an evolutionary scenario in which an ancestor of Evx and Mox was linked to the ProtoHox cluster, and that a tandem duplication of a large genomic region early in metazoan evolution generated the Hox and ParaHox clusters, plus the cluster-neighbors Evx and Mox. The large 'coupled' Hox-like cluster EvxHox/MoxParaHox was subsequently broken, thus grouping the Mox and Evx genes to the Hox clusters, and isolating the ParaHox cluster.

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Figures

Figure 1
Figure 1
Unrooted neighbor-joining phylogenetic tree. The tree relates the amino-acid sequences of the homeodomain plus 10 flanking residues on both sides in the Hox, ParaHox,EvxandMoxprotein sequences from mouse, amphioxus andDrosophila. The numbers refer to bootstrap values. Major groupings are indicated by color codes. Note thatMoxandEvxgroup together in a monophyletic group.
Figure 2
Figure 2
Phylogenetic trees.(a)Unrooted neighbor-joining tree;(b)rooted trees. The trees' topology suggests thatEvxandMoxgroup together as a sister group of the Hox/ParaHox clade. See text for discussion.
Figure 3
Figure 3
Synteny in the Hox/ParaHox regions in the human genome. The boxes represent the genes (only the 3'- and the 5'-most Hox genes have been depicted for clarity). Chromosomal positions are indicated below. Hox and ParaHox genes are depicted in purple,Moxin blue,Evxin green and non-homeobox genes such as those for collagens and tyrosine kinase receptors in light and dark gray, respectively.
Figure 4
Figure 4
Evolutionary scenario proposed for the origin and evolution of the extended Hox and ParaHox gene clusters. It implies anEvx/Moxancestor gene initially linked to theUrProtoHoxgene (step 1) that gives rise after duplication toEvxandMoxgenes, which is paralleled by the generation of primordial Hox and ParaHox clusters, forming a continuous array containing all the Hox-like genes (the 'coupled' Hox-like cluster; step 3). See text for details.
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