Mathematical1 and computational investigations2 show that chemical reaction networks are huge and include within them uncountably many autocatalytic cycles. These cycles can interact with each other much like species in biological ecosystems3 implying that dynamics of prebiotic chemical mixtures might have resembled ecological succession. Our research is structured around the idea that the earliest steps in the emergence of life occur when chemical succession (the chemical version of ecological succession) occurs when local patches (ecosystems) in spatially structured environments (meta-ecosystems) become targets of selection4. We have argued that chemical succession can gradually morph into familiar (Darwinian) evolution when they become organized as self-bounded individuals such as protocells and when they come to be dominated by the ecological interactions among cooperating genetic polymers. The Baum lab, thanks primarily to support from the National Science Foundation, uses innovative empirical and computation research to test all steps in this model (as shown in the figure).
1) Emergence of evolvable chemical mixtures
The theory we have developed suggests that out-of-equilibrium small molecule chemical mixtures can undergo long term changes in composition that resemble those seen in ecology or evolution. We conduct diverse laboratory experiments to look for evidence of these phenomena.
Our basic approach is to study the behavior of prebiotic soups – mixtures of compounds that are to some degree likely to have existed before life5. We incubate periodic soups (usually minerals) and use periodic dilution-and-replenishment to keep systems out of equilibrium. We original implemented this strategy, chemical ecosystem selection6, while tracking simple chemical features, which revealed evidence of complex non-linear chemistry7. We now use high-sensitivity liquid chromatography and tandem mass spectrometry (LC-MS) to obtain extremely detailed characterization of chemical dynamics and allow inferences regarding the underlying chemical reaction network. Current work is following up on preliminary evidence of heritability in the absence of genes8 and testing the hypothesis that small molecule combinatorial chemistry tends to multi-stability and extreme sensitivity to chemical perturbations.
2) Emergence of individuality
One of the most obvious differences between conventional ecosystems in a meta-ecosystem and cells/organisms in populations is that ecosystems are bounded extrinsically, whereas living systems make their own edges. This allows life to have a growth-and-division lifecycle that, among things, promotes cooperation among cellular components and suppresses cheating. We conduct computation and experimental research to better understand how individuation first arose and how primitive protocells might have evolved even in the absence of genes.
Our computational research is motivated by the cells-as-propagules hypothesis9, which proposes that, in environments subject to turnover in available sites, ecosystems chemical propagules composed capable of co-dispersing multiple cooperating autocatalytic cycles might be expected to arise and gradually acquire autonomy. We have shown that, in spatially structured environments, dispersal is an important consideration10. Now, partly in collaboration with Emily Dolson at Michigan State University, we are starting to model diverse mechanisms of co-dispersal assess whether protocells could gradually evolve rather than just pop into existence ready to grow and divide, as usually assumed. On the experimental front, graduate student Tymofii Sokolskyi is studying heritability in populations of artificial protocells as indicated by temporal dynamics11 and responses to artificial selection.
3) Emergence of genetic systems
Modern life depends on sets of polymers (proteins and nucleic acids) that cooperate to enable cells to grow and divide. By catalyzing specific reactions, polymers direct flux through metabolism and into the generation of new polymers. Moreover, nucleic acids have a specific ability to catalyze the formation of complementary strands, which serves as the basis for genetic inheritance. We are using experiments and computational modeling to understand how communities of cooperating polymers can emerge and complexify.
With collaborator, John Yin, we are using recursive wet-dry cycling (with dilution and replenishment) to elicit polymer formation and looking for evidence of autocatalytic feedback, where polymers formed after multiple cycles result in unexpected changes in composition. These investigations are at an early stage but should shed light on the intrinsic dynamics of polymerization cascaded. This work is complemented by a new, high-risk experimental approach we ate developing with support from the Alfred P. Sloan foundation. In a collaboration with David Beebe, a microfluidics engineer, we are developing a platform for imposing artificial selection on the emergent properties of droplets containing polymer populations. Combined with mathematical analysis of abstract polymerization systems12 and ongoing computational modelling of ecosystems of cooperating, catalytic nucleic acids we believe we will better understand how complex genetic systems composed of many long and highly efficient polymers can bootstrap themselves into existence during origins of life.
1 Gagrani et al. 2024; Gagrani and Baum 2024
2 Peng et al. 2022
3 Peng et al. 2020
4 Baum et al. 2023
5 Vincent et al. 2022
6 Baum and Vetsigian 2016
7 Vincent et al. 2019
8 Sokolskyi et al. 2024
9 Baum 2015
10 Plum et al. 2024
11 Sokolskyi et al. 2023
12 Gagrani and Baum 2024