We hypothesize that life began not with the first self‐reproducing molecule or metabolic network, but as a prebiotic ecology of co‐evolving populations of macromolecular aggregates (composomes). Each composome species had a particular molecular composition resulting from molecular complementarity among environmentally available prebiotic compounds. Natural selection acted on composomal species that varied in properties and functions such as stability, catalysis, fission, fusion and selective accumulation of molecules from solution. Fission permitted molecular replication based on composition rather than linear structure, while fusion (...) created composomal variability. Catalytic functions provided additional chemical novelty resulting eventually in autocatalytic and mutually catalytic networks within composomal species. Composomal autocatalysis and interdependence allowed the Darwinian co‐evolution of content and control (metabolism). The existence of chemical interfaces within complex composomes created linear templates upon which self‐reproducing molecules (such as RNA) could be synthesized, permitting the evolution of informational replication by molecular templating. Mathematical and experimental tests are proposed. BioEssays 28: 399–412, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

Biological objects are often constructive dynamic systems whose structures evolve as a consequence of their internal dynamics, which in turn is affected by the overall structure. As very few tools are presently adapted to tackle constructive dynamic systems, they constitute fascinating challenges for modeling/simulation. In cell biology, the secretory process in eukaryotic cells corresponds to this type of system, as it appears to autonomously generate new structures as a result of its molecular dynamics. Here I briefly review the only documented (...) case of a membrane-bounded intracellular compartment whose very existence strictly depends on its continued functioning. Indeed, the Golgi apparatus of the yeast Saccharomyces cerevisiae appears at steady-state as a continuously renewed set of transitory membrane-bounded structures that self-mature, rather than as a permanent entity. On the basis of this case and of recent advances in related molecular studies, a detailed model is proposed, that encompasses the birth of a yeast Golgi element and bridges its molecular and morphogenetic aspects. This model is extended to briefly outline three evolutionary inventions, from S. cerevisiae to another yeast, Pichia pastoris, on to plant, and on to animal cells: stacking, stabilizing and aggregating the primary Golgi elements. (shrink)