Scientists create bacterium with fewest number of genes

Researchers report the making of a living, replicating and stable cell that uses the minimum number of genes — 437 — to be considered biologically ‘alive.’

A technician performs a gene sequencing procedure at J. Craig Venter Institute. - File photo: Reuters

42, according to The Hitchhiker’s Guide To The Galaxy , is the answer to the “ultimate question of Life, the Universe, and Everything” but a team of biologists has shown that a better answer, to the ultimate question of life at least, maybe 473.

In Friday’s edition of the journal Science , researchers J. Craig Venter and Clyde Hutchinson and colleagues at the Venter Institute, California, report the making of a living, replicating and stable cell that uses the minimum number of genes — 473 — to be considered biologically ‘alive.’ In the natural world, no living organism is ever known to possess fewer than 1000 genes. The knowledge gained from this creation may be foundational to understand how organisms can be created from scratch.

Ever since the human genome — the complete sequence of genes that make up human DNA — was deciphered at the turn of the century, researchers have tried to understand the precise functions of these 25,000 genes and the way they network with other pieces of DNA in the cell to keep it functional.

Their efforts dovetail with the fundamental question of whether there is a minimum number of genes without which a cell would be dead. That question is also of immense practical interest as there is an entire subfield — called synthetic biology — that’s modifying bacteria and other microorganisms at the level of genes to make organic machines that can be employed to, for instance, clear oil spills and industrial enzymes. To build complex organisms would mean having a fine-grained understanding of why some genes are more essential than others. Scientists have sought to study bacteria of the

Mycoplasma genus — as it has relatively few genes and multiplies quite quickly — to analyse the relationship between genes and the chemical pathways they make.

From Syn 1.0 to Syn 3.0 In 2010, Mr. Venter and his team built and booted up the first self-replicating, synthetic bacterial cell (called Syn 1.0) through the sole chromosome (the storehouse of a cell’s DNA) of Mycoplasma mycoides — a bacterium with a relatively small genome — and transplanted it into Mycoplasma capricolum , from which they had previously extracted the DNA.

The hollowed-out

capricolum was re-programmed to behave like a

mycoides ; proof that genomes can be designed in the computer, chemically made in the lab, and transplanted into a recipient cell to produce a new, self-replicating cell controlled only by the synthetic genome. For its present work, the team reviewed scientific literature on the functions of each of the genes of Syn 1.0 and tried to remove every gene that didn’t seem essential. That, however, didn’t yield a stable cell.

Simultaneously, another team — through trial and error — sliced and diced the genome of Syn 1.0 and then identified which of its original 901 genes could be done away with. The final product of this stable cell with 473 genes is Syn 3.0. Intriguingly, they cannot yet explain why 149 of Syn 3.0’s 473 genes are essential to the survival of their test bacterium. “The JCVI-syn3.0 platform (as the software version of the test bacterium version is called) represents a versatile tool for investigating the core functions of life,” the authors said in their paper.

The next step would be to add genes, one by one, to this stripped-down genome and then see its effects on the constitution of the cell. “We are not claiming that this is the ultimate minimal genome,” Mr. Venter told Science .

Describing the research as a “huge contribution”, Mukund Thattai, a synthetic biologist at the Bengaluru-based National Centre for Biological Sciences, said the paper was significant because it showed up significant gaps in science’s understanding of how something as fundamental as a cell worked. He said that a reading of the paper revealed the ambition and effort that is required to build artificial genomes and test their viability. But, he cautioned, this did not mean that science was closer to making so-called artificial life in the laboratory. “Finding a precise answer to making a so-called minimal genome is an extremely important theoretical question…there is still too much unknown.”

This article has been corrected for a factual error.