The significance of Hox gene collinearity

Arthropods and vertebrates inherited their Hox clusters from an ancestral cluster of at least six genes already present in their last common ancestor, Urbilateria. Clustering and a common transcriptional direction are both likely features of the way that the gene complex first arose in a process of tandem gene duplication. Spatial collinearity (correspondence between ordering of Hox genes along the chromosome and their expression patterns along the head-tail axis) has been conserved in many animal groups and is likely to have been already present in Urbilateria. It is not known why the Hox cluster evolved with spatial collinearity. Four models are discussed. These vary in the significance they place upon Hox chromatin structure, and also on whether they propose that collinearity is primarily concerned with establishment or maintenance of Hox expression. Published proposals to explain spatial collinearity, which invoke enhancer sharing, chromatin closing or chromatin opening, are either problematic or can offer only partial explanations. In an alternative proposal it is suggested here that spatial collinearity evolved principally to maximise physical segregation, and thereby minimise incidence of boundaries, between active and inactive genes within the Hox cluster. This is to minimise erroneous transfer of transcriptional activity, or inactivity, between adjacent Hox genes.