The clustering of Hox genes is not necessary for their proper function

The Hox genes (also known as homeotic genes) play a crucial role in the development of animals, being involved in the determination of segment identity along the body axis. These genes were discovered in the fruit fly Drosophila melanogaster 90 years ago and have been found later in all animals, including humans. The Hox genes are arranged in the fly genome in a striking manner: they are clustered and their order is the same as that of the body segments they act upon. This organization is conserved in the genome of most animals where the Hox genes are arranged in a similar way as in the fly genome. Its conservation during hundreds of millions of years suggested that this organization must have an important effect on the function of Hox genes, although the cause of their clustering is still controversial.

A research group of the Department of Genetics and Microbiology of the Universitat Autònoma de Barcelona (Spain), led by Professor Alfredo Ruiz, with the colaboration of the Molecular Biology Center Severo Ochoa (Madrid, Spain), The University of Cambridge (UK), and the Children's Hospital Oakland Research Institute (USA) has found that the Hox gene complex has been rearranged differently in several Drosophila species. The function of Hox genes seems to be conserved despite the rearrangements. Thus Hox gene clustering in the Drosophila genome seems to be the result of evolutionary history more than that of functional necessity. The research will appear in this week's issue of the scientific journal Genome Research.

The scientists analyzed the genome region where the Hox genes are located in three Drosophila species, D. buzzatii, D. melanogaster and D. pseudobscura. These species possess differents organizations of the Hox gene complex as a result of the splits of the original complex present in the ancestor during the last 60 millions years. They also observed that the dispersion of Hox genes does not affect their expression and consequently their function. Therefore, at least in the fruit fly, the clustering of Hox genes is not necessary for their proper function.

The fruit fly Drosophila is not the only exception to the rule of ordered arrangement of Hox genes. Some worms and marine invertebrates also show breakages of the Hox gene complex. What do these organisms have in common with the fruit fly? The scientists point that in the embryo development of all these organisms, the Hox genes are not activated in a temporal succession, as it occurs in most animals, for instance humans. Rather, the Hox genes are activated more or less simultaneously according to a very fast embryo development. The simoultaneous expression of Hox genes appear to make their clustering at a single genome site unnecessary. Therefore the Hox gene complex in these animals is disintegrating.

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