Scientists create the simplest cell with only bare essentials for life and reproduction

Biologists have created a synthetic cell with only the bare minimum number of genes it needs to live and reproduce in a lab.

“What we have is an organism that is right now as simple as anything that can live on the planet,” said John Glass, a professor of synthetic biology at the J. Craig Venter Institute in California. Glass led the study, which was published in the journal Cell.

The feat is analogous to stripping a car down to its frame and only putting back the parts that are absolutely necessary to make the car drive — so no air conditioning, windshield wipers or windows. 

These cells contain only 480 genes, a very small number compared to the approximately 4,000 genes in an E. coli bacteria cell or 30,000 genes in our own cells.

The discovery will help scientists tease out what some genes do and also has practical applications, like testing how pharmaceuticals could alter cell function.

These minimal cells can also serve as platforms to test novel genetic pathways. One example that one of Glass’s collaborators is already working on is whether different genes cobbled together could improve carbon fixation, which is the process of taking carbon dioxide out of the atmosphere.

“I think that over the next decade, we’re going to see real progress in understanding the first principles of cellular life,” he told Quirks & Quarks host Bob McDonald. 

Team had to create new science

Scientists first discovered that cells make up all living things more than 350 years ago, but it’s only been since the 1930s that they started thinking about developing a minimal cell as a way to tease apart the first principles of cellular life. 

When Glass and his colleagues first started work on developing a synthetic cell containing only the genes necessary to survive in a laboratory environment, where food and nutrients were provided, he said the scientific techniques to do this didn’t exist yet.

John Glass, a professor of synthetic biology at the J. Craig Venter Institute, led the team that created the minimal cell. (J. Craig Venter Institute)

“This took us really about 15 years to get there and we had to invent whole new approaches for this science we call ‘synthetic biology’,” he said.

In 2016, his team announced their creation of a synthetic cell derived from a simple bacterial pathogen — Mycoplasma mycoides — that lives in goats. They stripped the bacterium with 901 genes to about half that number, so that a mere 473 genes remained.

To the naked eye, these original minimal cells appeared normal, but they were fragile to work with and in microscopic time-lapse videos, when they reproduced they weren’t dividing as expected.

Glass said some of the cells seemed to form spaghetti string shapes full of cytoplasm and extra chromosomes, “like there was no control of the amount of cell membrane being produced.” 

“When we saw these time lapse videos, we just said, ‘What the hell? What is going on here?'” 

The first minimal cells they created divided into abnormal shapes (left). After much trial and error, scientists at the J. Craig Venter Institute figured out they needed to add seven genes back in to restore their normal cell division (right). (James Pelletier / Cell )

Back to the cellular drawing board

The cells they had created had enough genes to live, but were obviously missing some critical genes necessary for reproduction.

Glass and his colleagues went back and took a fresh look at all other cells that they had created that had a few more than the minimal set of 473 genes.

A cell with with 19 additional genes reproduced normally, dividing into viable daughter cells, so they knew the answer they were looking for was in one or more of these genes. 

“When we looked at these 19 genes, we said, ‘Aha! It makes perfect sense.’ Two of these genes were well-known genes involved in bacterial cell division,” explained Glass.

Most of these [mystery] genes are present in all bacteria and a large fraction of them are present in all life forms on the planet, and yet we have no idea what they’re doing there.- Prof. John Glass, J. Craig Venter Institute

When they put those two genes back into their minimal cell, there was no improvement — the cells were still dividing in an odd manner. Clearly one or more of the other extra genes was necessary as well.

The researchers then went through the laborious process of adding genes one at a time and still didn’t find their answer.

It was only when they started trying multiple combinations of these 19 genes that they discovered there were actually seven genes that needed to be added back into the minimal cell to restore normal cell division. 

“What this means is that all seven of these genes are necessary for normal cell division, but they are not necessary for life,” said Glass. 

Figuring out the necessities of life

The result of this work was a new synthetic organism capable of reproduction, with a total of 480 genes. About half of the 480 genes in their new minimal cell are involved in chromosome maintenance and the production of proteins, about a quarter are involved in cell metabolism (producing energy).  But the function of the last quarter of this cells genome are still a mystery.

I think that over the next decade, we’re going to see real progress in understanding the first principles of cellular life.- Prof. John Glass, J. Craig Venter Institute

“Most of these [mystery] genes are present in all bacteria and a large fraction of them are present in all life forms on the planet, and yet we have no idea what they’re doing there,” Glass said.

Figuring out what these genes do could have big implications for fully understanding cellular biology, and the basic processes of life.  

“There’s never been a better time to be a biologist,” said Glass.  

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