DNA affects the phenotype of fuel-dependent coacervate droplets

TL;DR

This paper shows how DNA sequences can influence the behavior of synthetic cells, bringing them closer to Darwinian evolution.

Contribution

The study introduces genotype-driven selection in synthetic cells using DNA sequences that affect droplet behavior.

Findings

Guanine-rich DNA sequences kinetically trap droplets, altering dissolution rates and morphology.

Adenine-rich DNA sequences shorten droplet lifetimes through hybridization.

DNA sequences partition preferentially in coacervate droplets based on guanine and adenine motifs.

Abstract

Synthetic cells emulate fundamental biological behaviors, like growth, metabolism, and mobility, but have lacked genotype-driven selection, which is essential for Darwinian evolution. Here, we introduce libraries of short DNA sequences as genotypes into fuel-dependent peptide-RNA-based coacervate droplets, serving as synthetic cells. By sequencing, we identify sequences that partition in the droplets, revealing strong preferences for guanine-rich and adenine-rich motifs. These sequences affect the synthetic cell phenotype—adenine-rich sequences shorten droplet lifetimes through hybridization. In contrast, guanine-rich sequences kinetically trap droplets via peptide interactions, altering dissolution rates and morphology. This study demonstrates how genotype affects phenotype in synthetic cells, establishing essential design principles for achieving Darwinian evolution in minimal protocellular systems.

Synthetic cells mirror fundamental biological behaviors, like growth, metabolism, and mobility, but have lacked genotype-driven selection, which is essential for Darwinian evolution. Here, the authors introduce libraries of short DNA sequences as genotypes into fuel-dependent peptide-RNA-based coacervate droplets, identify sequences that partition on the droplets, and show they differentially affect the droplet phenotype.

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