Primitive genotype-phenotype coupling in fuel-dependent synthetic cells with an autocatalyst

The central dogma of molecular biology describes how genotype affects phenotype through the transfer of information from DNA to RNA to proteins and thus influences the cell’s traits. Reciprocally, the phenotype affects genotype success by influencing survival and reproduction. This relationship is crucial for Darwinian evolution. A major challenge in creating de novo life is establishing such a coupling. Here, we use fuel-dependent synthetic cells to explore primitive genotype-phenotype coupling. Droplets were endowed with a primitive genotype in the form of a replicator. The droplets filtered building blocks, decreasing replication error. The replicator, in turn, extended the droplet’s lifespan but only when produced in the droplets. Under fuel starvation, the droplet’s prolonged lifetime increased replication fidelity. We show that the primitive genotype helps the phenotype, which reciprocally helps the genotype, indicating a primitive genotype-phenotype coupling in a synthetic system. Future research should focus on the division of these compartments for replicator inheritance.