Developing a Chemical Ecosystem Paradigm for the Origins of Life (CESPOoL)

Recent theoretical work suggests that an early step in the origin of life was the emergence of ensembles of chemicals that interacted with one another to collectively propagate: in the presence of replenishing inputs of chemical precursors ("food") and energy, all chemicals in the ensemble are produced by the actions of other chemicals in the ensemble. Furthermore, advances in evolutionary theory suggest that, if these interacting molecular ensembles were spatially structured, for example by being adsorbed onto the surfaces of submerged minerals, they would be likely to evolve adaptively. Specifically, a process called neighborhood selection would tend to enrich for ensembles with progressively improved abilities to colonize new mineral grains. Since the ability to propagate (grow) and evolve adaptively are two key features of life, any ensemble having these properties would be "life-like," even if it were not organized into cell-like compartments and lacked any digital genetic encoding. The proposed research will use theory and laboratory experiment to better understand the origin and evolution of surface-associated, life-like, interacting molecular ensembles (SLIMEs). Guided by artificial ecosystem selection, a method used in microbial ecology, we will explore the behavior of sets of chemicals associated with mineral grains to see if they are capable of responding to an artificial selection pressure.

The chemical ecosystem selection paradigm for the origin of life (CESPOoL) project will use both mathematical modeling and empirical studies of real chemical networks to better understand the conditions under which SLIMEs might appear spontaneously and evolve towards higher complexity. Empirically, the consortium will implement a chemical ecosystem selection paradigm in multiple laboratories and use it to search through diverse minerals and chemical soups to find those that yield evidence of a SLIME. We will place a population of mineral grains in a chemical soup and then use serial transfer of a few seed grains (or their chemical cargo) to a new population of virgin grains. Such a procedure will tend to select over time for any SLIME that arose and was capable of moving from one grain to another. We will utilize two experimental approaches, one in which grain populations are incubated in microwell plates, and one which uses large populations of artificial liposomes. In either case, evidence that SLIMEs have arisen will come from systematic changes in the rate at which mineral surfaces become colonized by organic chemicals as well as responses to artificial selection for a target trait. If we find evidence of any SLIME we will determine its chemical composition and explore the degree to which the emergence of such a SLIME is predictable.

The empirical aspects of the CESPOoL project are high risk because it cannot be known in advance whether we will succeed in finding SLIMEs. However, even if we do not succeed in this goal, the project will advance our theoretical understanding of how non-cellular chemical systems can evolve adaptively and will pioneer a simple experimental paradigm that will be shared with other researchers so as to expand the search for chemical mixtures that can yield evolvable chemical ensembles.

The CESPOoL project takes a novel, multidisciplinary approach to the origin of life problem. Instead of focusing on the origin of particular structural (e.g., membranes) or chemical (e.g., nucleic acids, proteins) features of biological life we broaden the focus to encompass hypothetical systems, SLIMEs, which are much simpler than any living organism known, but which would nonetheless manifest the key properties of life and might represent a stepping stone to cellular life on Earth (or elsewhere in the Universe). As such, the project speaks to the goals of NASA's Exobiology and Evolutionary Biology program, "to understand the origin, evolution, distribution, and future of life in the Universe."


Life's Late Digital Revolution and Why It Matters for the Study of the Origins of Life. 
Baum DA, Lehman N. Life (Basel). 2017 Aug 25;7(3). Link

An Experimental Framework for Generating Evolvable Chemical Systems in the Laboratory
Baum DA, Vetsigian K. Orig Life Evol Biosph. 2017 Dec;47(4):481-497. Link

The Origin and Early Evolution of Life in Chemical Composition Space.
Baum, D.A. J Theor Biol. 2018 Nov 7;456:295-304. Epub 2018 Aug 12. Link

Mineral Surfaces Select for Longer RNA Molecules.
Mizuuchi R, Blokhuis A, Vincent L, Nghe P, Lehman N, Baum DA. Chem Commun (Camb). 2019 Feb 12;55(14):2090-2093. Link

Limited Sequence Diversity Within a Population Supports Prebiotic RNA Reproduction.
Mizuuchi R, Lehman N. Life (Basel). 2019 Feb 21;9(1). pii: E20. Link