Researchers sequence dark matter of life

Researchers have developed a new method to sequence and analyze the dark matter of life -- the genomes of thousands of bacteria species previously beyond scientists' reach, from microorganisms that produce antibiotics and biofuels to microbes living in the human body. Scientists from UC San Diego, the J. Craig Venter Institute and Illumina Inc., published their findings in the Sept. 18 online issue of the journal Nature Biotechnology. The breakthrough will enable researchers to assemble virtually complete genomes from DNA extracted from a single bacterial cell. By contrast, traditional sequencing methods require at least a billion identical cells, grown in cultures in the lab. The study opens the door to the sequencing of bacteria that cannot be cultured -- the lion's share of bacterial species living on the planet.

"This part of life was completely inaccessible at the genomic level," said Pavel Pevzner, a computer science professor at the Jacobs School of Engineering at UC San Diego and a pioneer of algorithms for modern DNA sequencing technology.

Pevzner, in collaboration with UC San Diego mathematics professor Glenn Tesler and computer science postdoctoral researcher Hamidreza Chitsaz, developed an algorithm that dramatically improves the performance of software used to sequence DNA produced from a single bacterial cell. These programs traditionally recover 70 percent of genes.

"The new assembly algorithm captures 90 percent of genes from a single cell. Admittedly, it is not 100 percent. But it's almost as good as it gets for modern sequencing technologies: today biologists typically capture 95 percent of genes but they need to grow a billion cells to accomplish it," said Tesler.

Bacteria play a vital role in human health. They make up about 10 percent of the weight of the human body and can be found anywhere from the stomach to the mouth. Some, like E. coli, can wreak havoc. Others help us digest. Yet others, recent studies have found, can change the way we behave by, for example, tricking us into eating more than we need. That's why it is crucial to analyze bacteria's genomes, which in turn help scientists understand bacteria's behavior.

Modern sequencing machines require DNA from one billion bacterial cells to produce a complete genome. Biologists usually grow the required amount of bacteria in cultures in the lab. That is how they obtained enough DNA to sequence E. coli. But a wide majority of bacteria -- 99.9 percent according to some estimates -- cannot be cultured in the lab because they live in specific conditions and environments that are hard to reproduce, for example in symbiosis with other bacteria or on an animal's skin.