Hox genes are expressed along the anterior-posterior (A/P) body axis in majority of animals , creating a unique A/P code which plays a pivotal role in segment specific morphogenesis. These homeodomain containing transcription factors are evolutionary conserved at the level of structure ,function and organization. This is best exemplified by their presence in clusters in all animals and provide A/P axial positional information during development. It was the discovery of homeobox in Drosophila and subsequent cloning in Xenopus revealed that the Hox genes that control the antero-posterior (A-P) axis were unexpectedly conserved, which subseduently lead to the birth of new field “evo-devo”.
Antennapedia mega cluster : From Jordi Garcia Fernandez – NRG
Diversity in body plans among animals is enormous and there is huge amount of evidence suggesting the origin of the Hox, gene cluster, and its subsequent evolution, has been crucial in mediating the major transitions in these body forms in evolution. The number of Hox genes ,their expression pattern and function played crucial role in the evolution of metazoan body plan. Comparative genomics studies of whole genome sequences of representative animals provide evidence that Hox cluster which provide valuable axial information was in fact embedded into a larger group forming a “megacluster” of antennapedia type homeobox genes in the ancestral bilaterian or Urbilaterian. There is growing evidence for the involvement of all the members ( Hox-NK-Parahox and extended hox genes) of this megacluster contributed to the body plan evolution.
Decoding the genetic tool kit of Urbilateria, the last common ancestor of invertebrates and vertebrates, will help us understand the contribution of gene loss and developmental constraints to the evolution of animal body plans. In the era of genomics as many genomes are completely sequenced allowing us to make strong conclusions about the history of life. The homeobox genes are particularly well suited for reconstruction of ancestral genomes because of their widespread conservation and robust family level phylogeny. The diversity among homeobox clusters are due to tandem duplications ,which resulted into functional cluster like Hox. Antennapedia forms the biggest cluster among homeobox and is very pivotal for the evolution of animal body plan development. Comparing genome sequences from different phyla provide convincing evidence that Hox clusters, extended hox genes and other homeobox clusters forms an integral part of Antennapedia mega cluster in ancestral bilaterian, but an extant animal with an intact megacluster has yet to be found. The antennapedia megacluster which was once united was dispersed into different set of genes owing to Chromosomal rearrangements in today’s animals.
Jordi Garcia Fernandez in his famous review on Hox genesis in Nature reviews Genetics provides a full evolutionary model for the genesis and evolution of the ANTP-class homeobox genes.Early in metazoan evolution, a ProtoANTP founder gene generated two genes by cis-duplication â€” ProtoHox-like and ProtoNK. Each gene was amplified by cis-duplication, giving rise to an array of Hox, ParaHox and NK clusters
Super Hox : by Thomas Butts, Peter W.H. Holland and David E.K. Ferrier ,TIG.
Last year there was a review in Trends in Genetics by Thomas Butts, Peter W.H. Holland and David E.K. Ferrier , where they compared the genome sequences of representative animals in order to reconstruct urbilateria – the starting point from which most present day animal lineages evolved. Bio informatics studies on various members of extant animals revealed remnants of ancestral Mega-cluster organization, apart from well known clusters of Hox,NK cluster and ParaHox cluster , but till now no current animal genomes are known that maintain the original set of ANTP-class genes (Hox-NK-Para Hox-extended Hox) in a single array. So in order to reconstruct the homeobox gene cluster that existed around the Hox cluster in the Urbilaterian , authors looked at the content and structural organization of the ANTP-class homeobox genes of the Florida lancelet (Amphioxus) and red flour beetle (Tribolium). The genomes of these two organisms served an advantage over the other bilaterians as they retained a greater extent of ancient genomic organization ( meaning diverged very less from ancestral urbilaterian) than is present in other sequenced bilaterian genomes, which allows the possibility of reconstruction of homeobox mega cluster present around Hox cluster in urbilaterian.The study indicated that Super-Hox cluster contained at least eight genes alongside the core Hox genes.
I will not go into complete details of analysis of two genomes and suggests you to read the complete articles mentioned in the reference below , but rather just try to summarize the important conclusion drawn by the study.
1) There were atleast 15 homeobox genes in the super hox cluster of urbilaterian genome , which includes 7 canonical hox genes and 8 other ANTP-class genes ( Mox, Hex, Ro, Mnx, En, Nedx, Dlx, Evx ).
2) The NK cluster of Urbilateria can be inferred to have contained nine genes: Msx, NK4, NK3, Lbx, Tlx, NK1,NK5, NK6 and NK7.
3) The ancestral homeobox Mega-cluster, had at least 24 genes in the form of two clusters in the urbilaterian: the 9-gene NK cluster and the 15+ gene Super-Hox cluster
3) Still its not clear from the available genome data that whether Super Hox and Nk were linked into one ultra super cluster in Urbilateria.
For Further reading and references :
1) The urbilaterian Super-Hox cluster.
Butts T, Holland PW, Ferrier DE.
Trends Genet. 2008 Jun;24(6):259-62.
2) The genesis and evolution of homeobox gene clusters.
Nat Rev Genet. 2005 Dec;6(12):881-92. Review.
3) Evo-devo: variations on ancestral themes.
De Robertis EM.
Cell. 2008 Jan 25;132(2):185-95. Review.
Link to David ferrier’s Lab
Web page of Jordi Garcia Fernandez
Eddy Robertis Lab
Presentation from David ferrier