Evolutionary Developmental Biology: Hox Gene Evolution


Hox genes are the homologues of the homeobox‐containing genes in the homeotic complex (HOM‐C) of the fruit fly Drosophila and encode transcription factors that play crucial roles in determining positional identity along the anterior–posterior body axis during animal development. Their expansion and duplication during metazoan evolution suggests that they have played a major role in generating animal diversity. In the protostomes, Hox genes are organised into a single cluster of genes that in some phyla has undergone gene loss and in others has become dispersed. On the contrary, cluster integrity is generally maintained in the deuterostomes, and during chordate evolution the single deuterostome cluster has undergone internal expansion as well as whole cluster duplications, generating animals with four or more clusters. Whereas these expansions and duplications are correlated with an increase in animal diversity, the main mechanisms driving metazoan evolution from a Hox perspective probably involve alterations in cis‐regulatory sequences of Hox genes and, to a lesser extent, changes in their coding sequences.

Key Concepts:

  • The prototype Hox gene potentially evolved from an ancestral NK homeobox gene very early in metazoan evolution.

  • Tandem and genome‐wide duplications generated the prototypical vertebrate Hox clusters.

  • Hox genes encode transcription factors that may have originally patterned bilaterian's evolving nervous system; however, as body organisation became more complicated and cells became more interdependent, Hox genes’ function may have co‐evolved with the function of other HB‐containing genes to jointly specify positional information in the derivatives of all three germ layers.

  • The clustering of Hox genes appears to be necessary for animals that use signalling pathways during development. This supports the presence of global control mechanisms that regulate all or a subset of genes within the cluster.

  • Organisms in which cells are primarily determined in early embryogenesis and develop autonomously begin to lose Hox cluster integrity.

  • The major morphological diversity in vertebrate lineages does not appear to be causally related to changes in the number or complement of the Hox genes. Therefore, Hox input into morphological diversity is likely to occur through altered cis‐regulation and/or downstream targets of Hox genes.

  • As the genome sequence of more species becomes available, the molecular phylogenetics of Hox cluster evolution will become clearer with an emphasis in understanding the evolution of the regulatory modules that partition Hox expression domains.

Keywords: homeobox (HB); gene cluster; metazoan; transcriptional regulation; colinearity; pattern formation; whole‐genome duplication (WGD); paralogous groups (PGs)

Figure 1.

Early branches of the metazoan cladogram showing the five main phyla leading up to bilaterian animals. Representatives of each phylum are indicated in parenthesis. Major features during the course of Hox gene evolution are indicated. ‘A’, anterior specifying gene; ‘C’, central specifying gene and ‘P’, posterior specifying gene.

Figure 2.

A cladogram of representative phyla from the Protostomes. The Arthropoda phyla has been further subdivided into two (Hexapoda and Crustacea) of its possible four subphyla. Hox genes are represented by coloured boxes with the first paralogue (Hox1) displayed on the left‐hand side of the figure. Where linkages are known, Hox genes are linked together by a black bar. In representatives where the overall cluster organisation is not known (such as in the shrimp and nautilus), linkages are not indicated. In some organisms, more than one paralogue has been identified such as in the nautilus which has two Hox5 and two Hox6 genes. In this figure, ‘A’ and ‘P’ correspond to anterior and posterior expression domains of the genes (i.e. spatial colinearity of the cluster).

Figure 3.

Representatives of the Deuterostomes that are made up of four phyla: Echinodermata, Hemichordata, Xenoturbellida (not shown) and Chordata. The phylum Chordata includes three subphyla: Cephalochordata, Urochordata and Vertebrata. The Vertebrata subphylum is expanded to show representative classes and orders used to highlight different evolutionary features of the Hox genes and their clusters as discussed in the text. The number of clusters in lampreys has not been resolved raising the possibility that they diverged after the first round of whole‐genome duplication (1R‐WGD), before the second round (2R‐WGD). Hox genes which are pseudogenes are indicated as white boxes. The first paralogue (Hox1) is displayed on the left‐hand side of the figure. ‘A’ and ‘P’ flanking the representative Hox clusters for tetrapods indicates anterior‐ and posterior‐expressed genes with respect to cluster organisation (i.e. spatial colinearity). Another round of WGD occurred during the radiation of the bony fishes and is indicated by an arrow labelled TSGD (Teleost‐specific genome duplication).



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Nolte, Christof, Ahn, Youngwook, and Krumlauf, Robb(Jul 2012) Evolutionary Developmental Biology: Hox Gene Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001063.pub3]