Combinatorial Limits of Transcription Factors and Gene Regulatory Networks in Development and Evolution

Gene Regulatory Networks (GRNs) consisting of combinations of transcription factors (TFs) and their cis promoters are assumed to be sufficient to direct the development of organisms. Mutations in GRNs are assumed to be the primary drivers for the evolution of multicellular life. Here it is proven that neither of these assumptions is correct. They are inconsistent with fundamental principles of combinatorics of bounded encoded networks. It is shown there are inherent complexity and control capacity limits for any gene regulatory network that is based solely on protein coding genes such as transcription factors. This result has significant practical consequences for understanding development, evolution, the Cambrian Explosion, as well as multi-cellular diseases such as cancer. If the arguments are sound, then genes cannot explain the development of complex multicellular organisms and genes cannot explain the evolution of complex multicellular life.