Plants and Animals

Scientists Build Synthetic Bacteria With Just 473 Genes

March 24, 2016 | by Robin Andrews

Photo credit: Only 473 genes are required for simple bacterial life to exist. Gio.tto/Shutterstock

What is the minimum requirement for life to exist? This is a hugely complex question, and researchers from almost every scientific field are working around the clock to attempt to at least partially answer it. One team, led by synthetic biologists at the J. Craig Venter Institute in La Jolla, California, appear to have come up with an answer.

As revealed in their groundbreaking study in the journal Science this week, by building a bacterial genetic sequence in a laboratory setting, they have identified just 473 genes that are essential for the simplest kind of independent bacterial life to exist. This information will now allow scientists to investigate the core functions inherent to almost all life on Earth with unprecedented insight.

“This bacterium contains only the genes necessary for life, and consists of just 473 genes,” Dr. Valda Vinson, deputy editor of Science, said in a press conference. “[This] gives us a versatile tool for investigating the core functions of life. But beyond this, the development of the methodology
could be applied to the construction of any cell – of a cell with any desired properties.”

The genome is the entire genetic sequence of a living thing. The chemistry, behavior, and reproduction of every cell is entirely determined by these collections of genes, many of which belong to species-specific cells, allowing them to thrive in the environment that they've evolved in. Significantly, however, some of these genes are considered essential for cell growth and reproduction, and researchers have been trying for decades to determine precisely which genes these are.

Syn3.0, the lab-made minimal genome within growing bacterial cells. The scale bar is one micron in length. Hutchison III et al./Science

Finding these would be a veritable “holy grail” of biology, giving researchers a blueprint for the “operating software” present in the cells of nearly every lifeform. Researchers think that the best way to uncover this so-called minimal genome is to look at very simplistic bacterial cells, and the Mycoplasma group has so far proven to be the perfect candidate.

One particular species, M. genitalium, has the smallest known genome of any living bacteria that can independently replicate. As a pioneering study in 1995 revealed, only 525 genes are found within each of these bacteria. (Smaller genomes exist, but these are found in bacteria that require a host.)

Not all of these genes are essential for M. genitalium to live and replicate, however, and researchers have been attempting to pinpoint the vital genes ever since. Fortunately, the science of genetics has made leaps and bounds in the last few decades; nowadays, genes aren’t just described, but synthesized in laboratories. The building blocks for DNA have long been known, and now researchers can physically construct it using chemistry techniques.

What the vital 473 genes are used for. The “unassigned” genes appear to be vital but their functions aren’t yet determined. Hutchison III et al./Science

The fast-growing M. myocoides, a closely related cousin of M. genitalium, was chosen for this particular study. Based on the real-life cell, the team synthetically constructed multiple versions of what they thought its minimal genome may be. They then implanted various fragments of it into another bacterial cousin, M. capricolum, and each individual gene’s possible essentiality was analyzed.

After an exhaustive investigation, the team came to the conclusion that just 473 genes are always required for simple bacterial life to exist. Without them, basic cellular functions required to preserve genetic information would simply not be possible.

Remarkably, the functions that these genes control are present in almost all life on Earth. Far from just helping researchers understand how life on Earth has evolved, this sought-after genetic blueprint may also reveal how it could begin. The authors of the study note that “as the detailed genetic requirements for life are discovered, it will become possible to design whole genomes from first principles, build them… and then bring them to life.”

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