Developmental control of transcriptional and proliferative potency during the evolutionary emergence of animals

• Published in: Developmental dynamics 2015-10, Vol.244 (10), p.1193-1201
• Main Authors: Arenas‐Mena, Cesar, Coffman, James A.
• Format: Article
• Language: English
• Subjects: Animals; Biological Evolution; Cambrian; Cell Proliferation; Chromatin - metabolism; chromatin evolution; Cyclin D; Gene Expression Regulation, Developmental; Gene Regulatory Networks; H2A.Z; multipotency; Regulatory Elements, Transcriptional; transdifferentiation
• ISSN: 1058-8388; 1097-0177
• DOI: 10.1002/dvdy.24305

It is proposed that the evolution of complex animals required repressive genetic mechanisms for controlling the transcriptional and proliferative potency of cells. Unicellular organisms are transcriptionally potent, able to express their full genetic complement as the need arises through their life cycle, whereas differentiated cells of multicellular organisms can only express a fraction of their genomic potential. Likewise, whereas cell proliferation in unicellular organisms is primarily limited by nutrient availability, cell proliferation in multicellular organisms is developmentally regulated. Repressive genetic controls limiting the potency of cells at the end of ontogeny would have stabilized the gene expression states of differentiated cells and prevented disruptive proliferation, allowing the emergence of diverse cell types and functional shapes. We propose that distal cis‐regulatory elements represent the primary innovations that set the stage for the evolution of developmental gene regulatory networks and the repressive control of key multipotency and cell‐cycle control genes. The testable prediction of this model is that the genomes of extant animals, unlike those of our unicellular relatives, encode gene regulatory circuits dedicated to the developmental control of transcriptional and proliferative potency. Developmental Dynamics 244:1193–1201, 2015. © 2015 Wiley Periodicals, Inc. Key Findings We propose that, in addition to the developmental gene regulatory networks that regionalize transcriptional states and determine the gene expression profile of specialized cells, the evolution of complex animals required the developmental control of both the transcriptional and proliferative potency of cells. We review and integrate evolutionary and mechanistic evidence from developmental gene regulatory networks, transcriptional multipotency and cell‐proliferation. We conclude that novel cis‐regulatory elements must exist in the genes encoding key chromatin and cell‐cycle regulators that stabilize differentiation and allow for coherent morphogenesis. Our hypothesis is testable by the presence of cis‐regulatory elements and network structures driving the developmental expression patterns of gene batteries that control chromatin and cell‐cycle regulation.