The Hox gene collinearity enigma has often been approached using models based on biomolecular mechanisms.
The biophysical model is an alternative approach based on the hypothesis that collinearity is caused by physical
forces pulling the Hox genes from a territory where they are inactive to a distinct spatial domain where they are activated
in a step by step manner. Such Hox gene translocations have recently been observed in support of the biophysical model.
Genetic engineering experiments, performed on embryonic mice, gave rise to several unexpected mutant expressions that
the biomolecular models cannot predict. On the contrary, the biophysical model offers convincing explanation. Evolutionary
constraints consolidate the Hox clusters and as a result, denser and well organized clusters may create more efficient
physical forces and a more emphatic manifestation of gene collinearity. This is demonstrated by stochastic modeling with
white noise perturbing the expression of Hox genes. As study cases the genomes of mouse and amphioxus are used. The
results support the working hypothesis that vertebrates have adopted their comparably more compact Hox clustering as a
tool needed to develop more complex body structures. Several experiments are proposed in order to test further the physical
Keywords: Chromatin, Hox collinearity, Limb bud, Invertebrate-vertebrate evolution.
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