Forever in New Genes

/ by Maggie Wittlin /

The never-ending genetic sequence baffles scientists

Think you can sequence the entire genome of group B strep? No? Good! You can’t, at least according to a recent paper published in the Proceedings of the National Academy of Sciences. Intriguingly, your inability isn’t so much a function of your lack of equipment, nor your cluelessness about the sequencing process. Rather, you can’t sequence this genome because it contains a potentially infinite number of genes.

A group of researchers at The Institute for Genomic Research in Rockville, MD, sequenced eight strains of group B Streptococcus. This isn’t the “flesh-eating strep” that keeps you from your morning-shower rendition of “Strangers in the Night”&mdsah;that’s group A. Group B strep is associated with meningitis in newborns and is the number-one cause of human neonatal infection. Even after sequencing several strains of the strep, the researchers observed that every newly-sequenced strain possessed genes not seen in previous strains, and so introduced more genes into the collective genome.

Hervé Tettelin, the paper’s lead author, said their data indicated that no matter how many new strains of the strep they analyzed, with every new strain they would find an average of 33 new genes. The researchers aren’t betting their first-borns on the number 33—their data supports an average of anywhere from 22 to 42 new genes per strain;. But the chance that they will reach a point where the average addition is zero genes per strain is less than .06 percent, according to their analysis. This implies that the strep has an open genome, and that the size of the genome will grow with every new strain.

Tettelin said that the genes unique to any one strain are probably acquired from other species.

“They look foreign compared to the rest of the genome,” he said.

Tettelin said the bacteria are good at obtaining new genes horizontally, from other bacteria, without the process of sexual reproduction.

Dr. Michael Cieslewicz, a doctor at Children’s Hospital Boston, the third author of the paper, said that the existence of an open genome means that the bacteria is versatile, robust and able to thrive under a variety of conditions.

“One implication of the vast genetic diversity found in [group B strep] is that there maybe many potential virulence factors that have not yet been identified that may provide [the strep] with the ability to invade and colonize new niches in the environment,” Cieslewicz said in an e-mail exchange.

Open genomes have huge ramifications for vaccine developers, forcing them to account for the protean abilities and vast biochemical diversity of even a single species of bacteria. Tettelin said that if vaccine developers realize they’re dealing with an open genome, they should study as many strains as possible.

Not every species of bacteria has an infinite genome. Tettelin cited anthrax as an example of a species that, with four strains, can be fully sequenced. But the story doesn’t end with group B strep; group A (the flesh-eating one) also appears to have an open genome. Countless other bacteria have not been sequenced exhaustively enough to determine whether their genomes are open or closed.

George Bennett, a professor of biochemistry and cell biology at Rice University, said that the findings of the study are consistent with the nature of bacteria. According to Bennett, “Bacteria in general are pretty adaptable as far as getting new genes in and having individual differences among closely related strains or isolates in a particular grouping.”

Yet Bennett was somewhat skeptical of the idea of a completely open genome.

“Infinite? That may be overdoing it a bit,” he said. “Maybe if you sequenced a hundred thousand strains or so you might begin having diminishing returns. But it would be a very large number.”

Originally published September 26, 2005

Tags complexity genetics research

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