Establishing homology criteria for regulatory gene networks: prospects and challenges.

One of the most remarkable discoveries to emerge from the field of developmental genetics is the observation that many regulatory genes and segments of their interactive networks (pathways) appear to have been conserved in several metazoan phyla. Determining whether these conserved regulatory networks are homologous, i.e. derived from an equivalent network in the most recent common ancestor, is critical to understanding comparisons between model system studies, and the evolution of metazoan body plans. To this end, I outline some of the evolutionary properties of regulatory networks, and propose both similarity and phylogenetic criteria that can be used to test the hypothesis that two regulatory networks are homologous. Furthermore, I propose that genetic networks can be treated as a distinct level of biological organization, and can be analysed together with other hierarchical levels, such as genes, embryonic origins and morphological structures, in a comparative framework. Examples from the literature, particularly the genetic regulatory networks involved in patterning arthropod and vertebrate limbs, are examined using the proposed criteria and hierarchical approach.