Researchers at Scripps Research have published two studies of synthetic life with a common goal to help explain two of…
Researchers at Scripps Research have published two studies of synthetic life with a common goal to help explain two of the greatest mysteries in the development of the earliest forms of life.
One is about how bacteria clustered into other cells to become mitochondria, power plants of cells with a nucleus, including all plants and animals. That study produced a symbiotic organism from yeast and the bacterium E. coli.
The other investigates how life was developed to use DNA as a carrier of heredity, from a supposed earlier stage where heredity was carried by RNA. That study gave a form of E. coli with about half of the genetic code in RNA, half in DNA.
The studies designed lifestyles that resembled these hypothetical earlier stages of life and observed how they worked, “said Peter G. Schultz, senior author of the two studies and the head of Scripps Research.
These two synthetic lifestyles are purely research projects, said Schultz.
The possibility of creating symbions could possibly be of commercial interest, he said. But it is not the intention of these two studies.
“It’s science for the sake of science.”
Introduction of strangers
The study of the origin of mitochondria was published on Monday. It raised the question of how invading bacteria could adapt to live symbiotic in cells with a nucleus called eukaryotic cells. Mitochondrial DNA is similar to that found in some bacteria, probably related to the ancestors of mitochondria.
In eukaryotes, the core stores and reproduces genetic information and mitochondria provide energy. The latter applies to chloroplasts, organelles in plants that perform photosynthesis. These are probably derived from free living photosynthetic bacteria.
Schultz and colleagues genetically designed a strain of baker’s yeast with defective mitochondria. They also designed a form of bacteria E. coli that needs the nutrient thiamine, which is provided by the yeast.
The bacterium was also designed to give energy to yeast and to resist being destroyed by the yeast as a pathogen. (Presumably, such defense of modern yeast would not have existed in ancient ancestors).
“We started with E. coli and yeast because they are genetically dry organisms ̵
1; easy to manipulate in the lab,” said Schultz.  Then they introduced the two and looked at.
Some of the synthetic organisms survived and produced daughter cells. This took place for more than 40 generations, without signs that it ended, said Schultz. In addition, the modified E. coli bacteria began to accumulate mutations that allowed them to survive better within the yeast.
The researchers continued the work by removing bacterial genes to make other nutrients fed by the yeast and found that they could still get a successful symbiosis. They have successfully removed 10 genes so far.
The Schultz team wants to further reduce symbiotic E. coli genomes. The bacterium has thousands of genes, while mitochondrial genes have only 37 genes.
They also work to recapitulate the origin of chloroplasts. The nearest equivalent to chloroplasts is today cyanobacteria, also called blue-green algae. These have also been designed to be dependent on yeast and yeast to get energy from the cyanobacteria.
The results of the survey should be completed in a few months, Schultz said.
Return to RNA ]
E. coli was also used in a study published earlier where it was shown that much of its genome could be replaced by RNA and still survive. The study was published August 30 in the Journal of the American Chemical Society, or JACS.
The researchers could construct a derivative of E. coli with half of its genetic code carried in RNA, the rest in DNA. 19659002] This result was a surprise. The original objective of the study was to produce DNA with different “letters” than the four letters used in nature, A, C, G, and T.
However, after randomly mutating their constructed tribes and seeing the unexpected appearance of genomic RNA, saw a potential link to the origin of life in RNA. A widely accepted hypothesis about the origin of life claims that RNA came before DNA, the so-called “RNA-world” hypothesis.
“So how do you go from an RNA-based world to a living organism where DNA carries genetic information?” Schultz said.
You rose, probably. This means that a hybrid form of life may have existed, with its genetic instructions partly in DNA and partly in RNA. And it had a strong resemblance to what the researchers had produced from an accident.
“It was shocking,” said Schultz. “It was shocking because no-one has ever seen this before.”
The first thought was that it was discovered that RNA was a contamination. Several tried to steer it out. Thereafter, the researchers investigated the function of this hybrid molecule.
“We still do not really understand how it works,” said Schultz.
Proteins from this hybrid DNA / RNA genome were also mutated at a much higher rate than pure DNA organisms, found the study. This indicates that in the earliest stages of life, the rate of mutation was also high, which caused extensive changes in the cellular machine, Schultz said.
The goal is now to make deliberate changes to the bacterium and see if the results can be expected.
“If we can rationally design a similar organism from the outset, we can begin to understand better,” said Schultz.
The symbiotic yeast and bacterial study was a collaboration between Scripps Research, University of California, San Francisco, the Oak Crest Institute of Science and the Genomics Institute of Novartis Research Foundation. It was funded by the Calibr arm of Scripps Research; Department of Energy; National Institute of Health; and the Chan Zuckerberg Initiative Human Cell Atlas program.
The hybrid DNA / RNA study was a collaboration between Scripps Research, the Bay Area Innovation Center and the University of California, Irvine. It was funded by Calibr.