Life

The inner workings of a supposedly simple bacterial cell have turned out to be much more sophisticated than expected.

An in-depth "blueprint" of an apparently minimalist species has revealed details that challenge preconceptions about how genes operate. It also brings closer the day when it may be possible to create artificial life.

Mycoplasma pneumoniae, which causes a form of pneumonia in people, has just 689 genes, compared with 25,000 in humans and 4000 or more in most other bacteria. Now a study of its inner workings has revealed that the bacterium has uncanny flexibility and sophistication, allowing it to react fast to changes in its diet and environment.

"There were a lot of surprises," says Peer Bork, joint head of the structural and computational biology unit at the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany. "Although it's a very tiny genome, it's much more complicated than we thought."

Master controllor

The biggest shock was that the organism gets by with just eight gene "switches", or transcription factors, compared with more than 50 in other bacteria such as Escherichia coli. Transcription factors are generally thought of as the key components enabling living things to respond to environmental conditions by switching genes on and off.

So how does the cell get by with so few "master controllers"? One possibility is that stretches of "antisense RNA" – basically genes copied back to front – stand in for the transcription factors as gene switches.

An even more intriguing possibility is that chemicals thought to serve as food – such as the sugar-like substance glycerol – are signalling messengers in their own right, helping to fine-tune what the cell does and how it reacts to changes in its environment.

Family surprise

Another unexpected discovery was that bacterial genes grouped together in clumps or families called "operons" don't work as had been thought. The assumption was that if there are four genes in an operon they always work in unison, but the new analyses show that only one, or perhaps two, operate at any one time.

Even more surprising, the proteins the genes make don't necessarily always couple with their nearest neighbours – again contrary to previous assumptions. Instead, they often join up with proteins originating from other, distant operons, vastly increasing the bacterium's flexibility and versatility when faced with a changed environment.

"What we've learned is that if you want to understand any cell and the protein complexes it makes, you can't infer what happens from the order the genes are in," says Anne-Claude Gavin, also at EMBL, who co-led the project.

The protein analysis also revealed that the bacterium compensates for having so few proteins by employing each one in a multitude of functions. "There's lots of moonlighting going on, as each protein has lots of jobs to do," says Bork.

Motor position

The researchers produced a "CT scan" of the bacterium, which shows the positions of some its major molecular "motors", such as ribosome protein factories (see image, above). The image was created by taking an electron tomograph of the bacterium itself.

This initially revealed no more than indistinct blobs. But by using profiles of electron density of similar molecular machines, taken from the scientific literature, and superimposing them on the tomograph image, the researchers were able to identify which blobs were which motors.

The hope is that when the resolution of such images is eventually increased, many of the smaller motors will also be identified, Bork says.

It may even one day be possible to monitor what is going on in real time, establishing exactly how the genes and proteins work together. If this can be achieved, it could help researchers build artificial organisms.

Journal references: Science, DOI: 10.1126/science.1176951 (how M. pneumoniae's 700 genes are coordinated and controlled); DOI: 10.1126/science.1177263 (how the bacterium extracts energy and building materials from food); DOI: 10.1126/science.1176343 (how proteins made by the 689 genes are bolted together to perform functions)

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