New Gene Sequencing Technique Opens the Doors for Studying Elusive Bacteria

By Veronique Greenwood | September 19, 2011 1:49 pm

bacteria
If bacteria can’t grow in a Petri dish, sequencing them is difficult.

What’s the News: Want the genome of a bacterium you found in your belly button? Or, for that matter, of a bacterium producing a promising new antibiotic? Well, unless you can get it to thrive in a Petri dish and create a billion sister cells for analysis, you’re out of luck.

But sequencing the genomes of notoriously finicky bacteria, like those on skin, could be on the horizon with a new procedure that bypasses the Petri dish step. Pairing a new algorithm with an earlier technique, scientists from the Venter Institute and their collaborators can now get all that information from a single cell.

How the Heck:

  • The team has been working on sequencing the genomes of single cells for a while and had developed a technique that, instead of requiring a billion cells, simply replicates fragments of the genome of a single cell over and over in a test tube until there’s a billion-cells’ worth of DNA.
  • But the replication is haphazard: some fragments are replicated many times while only one or two copies exist of others. This meant that legitimate sections of the genome could be discarded as random noise.
  • Now the team has created an algorithm that compensates for that by hanging on to the least-replicated sections. Adding it to their previous method, they sequenced the genome of a single E. coli cell and found that the technique produced a sequence with 91% percent accuracy. That’s comparable to the 95% accuracy promised by the billion-cell route.
  • Next they took on the genome of a marine bacterium that had never before been sequenced, a kind of deltaproteobacterium. Looking at its genes, they were able to deduce how it moves and in what environments it would thrive.

What’s the Context:

  • There are more bacterial cells in the human body than there are human cells, living in bustling colonies in our guts, skin, and elsewhere. And in recent years, we’ve realized that the bacterial menageries on and in our bodies play roles in everything from digestion to emotion.
  • Growing up bacteria harvested from stool samples or cheek swabs and sequencing the genomes of our “microbiomes” is an exciting prospect—by examining the genes of our symbiotic bacteria we can begin to learn how they influence mood, for instance, work on a molecular level, and why humans seem to fall into one of three types, similar to blood types, when it comes to gut bacteria.
  • Also, the natural world, especially the ocean and the soil, contains thousands and thousands of bacterial species that scientists hope to mine for useful new compounds.
  • But many bacteria—as many as 99.9 percent of the species in the world, in fact—are so exquisitely tuned to their environments that they can’t survive once they’re removed. Thus, whatever is grown in a Petri dish may not capture many of the species we might want to study, whether the intent is finding new drug candidates produced by marine bacteria or understanding the ecology of our eyebrows.
  • This accurate single-cell sequencing technique is a perfect match for those organisms, and we can expect further papers from this group detailing what they find in everything from sea water to soil to human skin.

Reference: Hamidreza Chitsaz, et al. Efficient de novo assembly of single-cell bacterial genomes from short-read data sets. Nature Biotechnology, 2011; DOI: 10.1038/nbt.1966

Image courtesy of IRRI images / flickr

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