he answer: 473. The question: What is the fewest number of genes necessary for life?
That may sound like the DNA version of “How many angels can dance on the head of a pin?” but in a study published in Science on Thursday genetics pioneer J. Craig Venter and colleagues argue that the answer — and the research behind it — not only sheds light on fundamental questions such as what makes something alive, but also has practical implications for genome editing.
You’ll want to know:
The study is the culmination of a two-decades-long effort to see if nature included any unnecessary genes in Mycoplasma genitalium, a bacterium whose 525 genes give it the fewest of any known organism.
In 2010, Venter’s team built a Mycoplasma genome from off-the-shelf parts, stuck it into a different bacterium whose own DNA had been removed, and got the synthetic cell, called Syn 1.0, to grow and reproduce. They then guessed what a minimal genome for Syn 1.0 might contain, built it in eight segments, and began adding, removing, and shortening segments until they identified the essentials.
They ended up with 473 genes and a working cell, Syn 3.0. (Syn 2.0 didn’t work out.)
Why it matters:
Knowing how few genes, and which ones, are needed to run life’s processes is a cool finding in basic biology. But for Venter, it was “very, very humbling” that his team couldn’t figure out the function of 149 of the genes, he told reporters. That suggests there are undiscovered reactions essential for life.
Subbing genes into and out of Syn 1.0 also showed that DNA that seemed to have one essential function did something else depending on which other genes were present. That undermines what Venter called a “gene-centered” view, exemplified by claims that gene X causes disease Y.
Instead, a “disease gene” in one genome might be a healthy gene in another, and genome-editing techniques such as CRISPR might never work to understand the genetic basis of, let alone treat, common complex diseases. “It’s vastly premature to think about editing the human genome until we know a whole lot more,” Venter said.
What they’re saying:
“Very profound,” an “impressive feat,” “a big leap forward,” and “a tour de force” were only some of the encomiums from scientists not associated with the study, as gathered by the Genetic Expert News Service.
But keep in mind:
The 473 genes are not the minimal genome. They are a minimal genome. If Venter’s team grew the bacteria in different conditions, or settled for slower growth — the population of bugs with 473 genes doubles every three hours — they’d have a different set.
This is an advance in the field of synthetic biology, whose prize is coming into view: using off-the-shelf chemicals to create a living cell.