Yeast cell engulfing E. coli bacteria, symbolizing engineered symbiosis and energy transfer.

Rewriting Evolution: Engineering a Symbiotic Future Within Cells

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Nico Varela in Science & Nature August 2025 • 5 min read.

"Can we fast-track organelle evolution by creating artificial endosymbiosis?"


Imagine mitochondria, the powerhouses of our cells, having a completely different origin story. Endosymbiotic theory proposes that these vital organelles were once free-living bacteria engulfed by a host cell billions of years ago. This partnership forever changed the course of eukaryotic evolution, paving the way for complex life as we know it. But can we recreate this ancient merger in the lab?

Researchers are now attempting to fast-forward evolution by engineering a modern version of this endosymbiosis. Their approach? Creating a symbiotic relationship between Escherichia coli (E. coli) bacteria and Saccharomyces cerevisiae (baker's yeast). This groundbreaking research aims to shed light on the earliest stages of mitochondrial evolution and explore the potential for creating novel cellular systems.

By manipulating the genomes of both organisms, scientists are forcing them to rely on each other for survival. The result is a fascinating cellular chimera, a system that not only helps us understand the past but also opens doors to the future of synthetic biology, where we might design and build cellular systems from the ground up.

How to Build a Cellular Partnership: Engineering Endosymbiosis

Yeast cell engulfing E. coli bacteria, symbolizing engineered symbiosis and energy transfer.

The core of this research involves making E. coli and yeast dependent on each other. Researchers engineered E. coli to provide ATP, the energy currency of the cell, to a respiration-deficient yeast mutant. Simultaneously, the yeast supplies thiamin, an essential nutrient, to a specially designed E. coli strain that can't produce it on its own. This creates a reciprocal dependency: the yeast needs the E. coli for energy, and the E. coli needs the yeast for thiamin.

However, simply putting bacteria inside yeast isn't enough. Yeast cells have defense mechanisms to break down foreign invaders. To prevent the E. coli from being destroyed, the scientists introduced SNARE-like proteins into the bacteria. These proteins, borrowed from intracellular pathogens, help the E. coli evade the yeast's degradation pathways, allowing them to survive and thrive within their host.

The key steps in creating this engineered endosymbiosis include:
  • Engineering E. coli to express an ADP/ATP translocase, allowing it to provide ATP to the yeast.
  • Creating a thiamin auxotrophic E. coli strain, making it dependent on the yeast for this essential nutrient.
  • Expressing SNARE-like proteins in E. coli to prevent degradation by the yeast's lysosomes.
  • Selecting for stable yeast-E. coli chimeras that can grow on a nonfermentable carbon source.
The resulting chimeric system proved remarkably stable, maintaining the symbiotic relationship for over 40 generations. Using advanced imaging techniques like fluorescence microscopy and X-ray tomography, researchers could visualize the E. coli endosymbionts within the yeast cells, confirming their presence and structural integrity.

A New Playground for Evolutionary Experiments

This engineered yeast-E. coli system offers a powerful platform for studying the intricate dance of host-endosymbiont adaptation. By manipulating the genomes of both organisms, researchers can experimentally dissect the evolutionary pressures and genetic changes that led to the highly reduced mitochondrial genome we see today.

One of the most exciting avenues for future research is to explore genome reduction in the E. coli endosymbiont. By gradually removing non-essential genes and forcing the bacteria to rely on the yeast cytosol for essential metabolites, scientists can mimic the evolutionary process that streamlined the mitochondrial genome over millions of years.

Ultimately, this research transcends the boundaries of evolutionary biology. It provides a foundation for creating synthetic organelles with tailored functions, opening up possibilities for novel biotechnologies and biomedical applications. Imagine engineering cells with enhanced energy production, customized metabolic pathways, or the ability to synthesize valuable compounds. The era of designer organelles may be closer than we think, thanks to these pioneering efforts in engineering endosymbiosis.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1073/pnas.1813143115, Alternate LINK

Title: Engineering Yeast Endosymbionts As A Step Toward The Evolution Of Mitochondria

Subject: Multidisciplinary

Journal: Proceedings of the National Academy of Sciences

Publisher: Proceedings of the National Academy of Sciences

Authors: Angad P. Mehta, Lubica Supekova, Jian-Hua Chen, Kersi Pestonjamasp, Paul Webster, Yeonjin Ko, Scott C. Henderson, Gerry Mcdermott, Frantisek Supek, Peter G. Schultz

Published: 2018-10-29

Everything You Need To Know

1

What is the primary goal of the research described?

The research focuses on creating a symbiotic relationship between two organisms: Escherichia coli (E. coli) bacteria and Saccharomyces cerevisiae (baker's yeast). This artificial endosymbiosis mimics the ancient process where mitochondria, the powerhouses of cells, originated from free-living bacteria. The goal is to understand how this merger occurred and to explore the potential for creating novel cellular systems.

2

How do scientists create a symbiotic relationship between E. coli and yeast?

Scientists engineer E. coli to provide ATP, the cell's energy currency, to a respiration-deficient yeast mutant. Simultaneously, the yeast supplies thiamin, an essential nutrient, to a specially designed E. coli strain. This creates a reciprocal dependency, where the yeast needs the E. coli for energy and the E. coli needs the yeast for thiamin. This interdependence is a key step in forming the symbiotic relationship.

3

What role do SNARE-like proteins play in this engineered endosymbiosis?

SNARE-like proteins are introduced into the E. coli. These proteins, borrowed from intracellular pathogens, help the E. coli evade the yeast's defense mechanisms that would otherwise break down the bacteria. This is crucial for the survival of the E. coli within the yeast, allowing the symbiotic relationship to establish and persist.

4

How does this engineered system contribute to understanding evolution?

The engineered yeast-E. coli system enables the study of host-endosymbiont adaptation. Researchers can manipulate the genomes of both E. coli and Saccharomyces cerevisiae. This allows them to investigate the evolutionary pressures and genetic changes that led to the highly reduced mitochondrial genome. The stability of this system over many generations provides a platform for observing the evolutionary process in real-time.

5

What are the broader implications of this research?

This research has implications for understanding the origins of complex cells and advancing synthetic biology. By recreating the endosymbiotic event that led to mitochondria, scientists gain insights into the early stages of evolution. Furthermore, this work opens doors to designing and building novel cellular systems, potentially leading to new biotechnological applications. The engineered yeast-E. coli system serves as a model to fast-forward evolution.

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