Artificial life created in lab needs a minimum 473 genes to survive and reproduce

The minimal cell has a third of its genes whose roles remain mysterious.

The magic number to create life that can survive and reproduce turns out to be 473. That is the number of genes that were left behind after biologists working with a synthetic cell started paring down genes from the 901 numbers that made the bacterial cell.

Not only is the work a step towards knowing the functions of genes, the work led by the J Craig Venter Institute also gives a glimpse of early days of evolution of life here on Earth and possibly elsewhere. It shows that the environment is important in the selection of genes.

"It's going to be very interesting looking at the different (gene) functions that now exist and what it takes to put together a living, functioning, self-replicating cell to see where they all came from and how earlier life might have developed," Venter Institute founder and chief executive Craig Venter told Discovery News.

"This entire program started with ones and zeros (in a computer) and four bottles of chemicals," Venter said. A DNA-sequencing machine could easily decipher the code of life on any planet and send back the code to Earth, he said.

However, even with as few as 473 genes that the minimal cell contains, the team has not been able to decipher the functions of 149 genes, crucial as they are.

"If we take out any of those genes, the cell dies," Venter told DNews. "We expected some of those because we see them in every life form, but I expected 5 to 10 percent at most. The fact that we don't know this much biology is very humbling."

Scientists at the Craig Venter Institute and its commercial arm, Synthetic Genomics Inc., created in 2010 the synthetic cell JCVI-syn1.0 and which has 901 genes. The cell was closely identical to the naturally occurring bacteria Mycoplasma mycoides, which has a short genetic code thanks to its dependence on the host cell.

They then devised a hypothetical genome by organizing the genetic code into segments that could be tested one at a time and classified as essential or non-essential. Replication requirement added genes to the minimal code.

What they ended up with was JCVI-syn3.0. But even that cell remains partly mysterious in the functions of some genes. Above all, they saw how a gene cannot be assigned a single function. Often they have multiple roles that come into play at various stages of the cell's biology.

"Life is much more like a symphony orchestra than a piccolo player," said Venter.

Venter helped map the human genome in 2001 and also created the first synthetic cell in 2010 with the present team. It demonstrated that genomes can be designed on a computer, made in a laboratory and transplanted into a cell to form a new, self-replicating organism. Arriving at the minimal cell in a trial and error method was the next task that took five years. But understanding the roles of genes has proved more difficult.

Microbiologist Clyde Hutchison, lead author of the study in the journal Science, said the goal is to figure out the functions of all the genes and make a computer model to predict how this life will evolve in different environments or with additional genes.

"It's important to realize there is no cell that exists where we know the functions of all the genes," Hutchison told Reuters.

Much like gene editing techniques like Crispr that have raised concerns of designer babies and unethical tampering with human embryos, the present work has also sent alarm bells ringing.

The environmental group Friends of the Earth point to the lack of government regulations in synthetic biology and gene editing technologies.

"Living organisms like bacteria are not machines to be rewired," said Dana Perls, an official of the group. "Not even the scientists know the biological function of 149 of these genes, which raises safety concerns. If we don't fully understand the science, it is more difficult to manage biosafety concerns."