A general theory of individuated multicellularity

Changes in gene expression are thought to regulate the differentiation process intrinsically through complex epigenetic mechanisms. In fundamental terms, however, this assumed regulation refers only to the intricate propagation of changes in gene expression or else leads to logical inconsistencies. The evolution and self-regulatory dynamics of individuated multicellularity also lack a unified and falsifiable description. To fill this gap, I computationally analyzed publicly available high-throughput data of histone H3 post-translational modifications and mRNA abundance for different Homo sapiens, Mus musculus, and Drosophila melanogaster cell-type/developmental-periods samples. My analysis of genomic regions adjacent to transcription start sites generated a profile from pairwise partial correlations between histone modifications controlling for the respective mRNA levels for each cell-type/developmental-period dataset. I found that these profiles, while explicitly uncorrelated to transcript abundance by construction, associate strongly with cell differentiation states. This association is not expected if cell differentiation is, in effect, regulated by epigenetic mechanisms. Based on these results, I propose a falsifiable theory of individuated multicellularity, which relies on the synergistic coupling across the extracellular space of two stochastically independent \"self-organizing\" systems constraining histone modification states at the same sites. This theory describes how the multicellular individual--understood as an intrinsic, higher-order constraint--emerges from proliferating undifferentiated cells, and may explain the intrinsic regulation of gene transcriptional changes during cell differentiation and the evolution of individuated multicellular organisms.