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Scripps Research scientists have published two studies on synthetic life with the common goal of explaining two of the greatest mysteries of the evolution of the oldest life forms.
One is the way in which bacteria have fused into other cells to become mitochondria, nucleus cell power plants, including all plants and animals. This study produced a symbiotic organism from yeast and E. coli bacteria.
The second explores how life evolved to use DNA as a carrier of heredity, from a presumed earlier stage in which heredity was carried by RNA. This study yielded a form of E. coli of which about half of the genetic code was contained in RNA and the other half in DNA.
Studies have built life forms that mimic these hypothetical steps and showed how they work, said Peter G. Schultz, lead author of both studies and director of Scripps Research.
These two synthetic life forms are purely research projects, Schultz said.
The possibility of creating symbionts could potentially become a commercial interest, he said. But this is not the purpose of these two studies.
"It's science for science."
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The study on the origin of mitochondria was published Monday. He addressed the question of how invasive bacteria could adapt to life in symbiosis in nucleus cells called eukaryotic cells. Mitochondrial DNA resembles that of some bacteria, probably related to the ancestors of mitochondria.
In eukaryotes, the nucleus stores and reproduces genetic information and mitochondria provide energy. This is true for chloroplasts, the organelles of plants performing photosynthesis. These are probably from free photosynthetic bacteria.
Schultz and his colleagues have genetically engineered a strain of baker's yeast with defective mitochondria. They have also developed a form of E. coli bacteria that needs thiamine, a nutrient provided by yeast.
The bacterium has also been designed to provide energy to the yeast and prevent its destruction by yeast as a pathogen. (Presumably, such defenses of modern yeast would not have existed in ancient ancestors).
"We started with E. coli and yeast because they are genetically manipulable organisms – easy to handle in the lab," said Schultz.
Then they introduced both and watched.
Some of the synthetic organisms survived and produced daughter cells. This has been happening for over 40 generations, with no sign of an end, said Schultz. In addition, the modified E. coli bacterium even began to accumulate mutations that allowed it to survive better in yeast.
The researchers deepened the work by removing bacterial genes for the manufacture of other nutrients provided by the yeast, and discovered that they could still achieve a successful symbiosis. Until now, they have managed to delete 10 genes.
The Schultz team wants to further reduce the symbiotic genomes of E. Coli. The bacterium has thousands of genes, while the mitochondrial genomes have only 37 genes.
They also work to summarize the origin of chloroplasts. Cyanobacteria, also called blue-green algae, are the closest equivalent of chloroplasts. These have also been designed to depend on yeast and yeast to derive energy from cyanobacteria.
The results of this research should be ready in a few months, said Schultz.
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E. coli was also used in a previously published study where it was shown that a large part of its genome could be replaced by RNA and continue to survive. This study was published Aug. 30 in the Journal of the American Chemical Society, or JACS.
Scientists were able to create a derivative of E. Coli whose half of the genetic code is contained in the RNA, the rest in the DNA.
This result was a surprise. The initial objective of the study was to produce DNA with "letters" different from the four letters used in nature, A, C, G, and T.
But after randomly mutating their modified strains and finding the unexpected appearance of genomic RNA, scientists have discovered a potential link with the origin of life in RNA. A widely accepted hypothesis about the origin of life argues that RNA came before the DNA, the so-called "world of RNA" hypothesis.
"So how do you go from an RNA-based world to a living organism where DNA carries genetic information?" Schultz said.
In stages, presumably. This means that a hybrid life form may have existed, carrying his genetic instructions partly in the DNA and partly in the RNA. And it looked a lot like what the scientists had produced by accident.
"It was shocking," Schultz said. "It was shocking because no one had ever seen it before."
The first thought was that the detected RNA was a contaminant. Several experiences have spread it. The scientists then explored the function of this hybrid molecule.
"Frankly, we still do not quite understand how it works," said Schultz.
The study found that the proteins in this hybrid DNA / RNA genome also mutated much faster than organisms with pure DNA. This suggests that in the early stages of life, the mutation rate was also high, leading to profound changes in the cellular machinery, Schultz said.
The goal now is to make deliberate changes to the bacteria and see if the results can be predicted.
"If we can now rationally design a similar organism from scratch, then we can begin to understand it better," Schultz said.
The symbiotic yeast / bacteria study was a collaboration between Scripps Research, the University of California at San Francisco, the Oak Crest Institute of Science, and the Genomics Institute of the Novartis Research Foundation. It was funded by the Calibr branch of Scripps Research; the energy department; National Institutes of Health; and the Human Cell Atlas program of the Chan Zuckerberg initiative.
The hybrid DNA / RNA study was a collaboration between Scripps Research, the Bay Area Innovation Center and the University of California at Irvine. It was funded by Calibr.
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