Could bacterial infections be altering our DNA?

Scientists have discovered the genome of a bacterial parasite incorporated into the genome of its host species, according to a report published recently in Science.

The research, conducted at the University of Rochester and the J Craig Venter Institute, shows that lateral gene transfer — the movement of genes between unrelated species — may happen much more frequently between bacteria and multicellular organisms than scientists previously believed. Such large-scale heritable gene transfers may allow species to acquire new genes and functions extremely quickly, according to a principle investigator of the study, Jack Werren. If so, this could pose dramatic implications for evolution and disease control.

The results also have serious repercussions for genome-sequencing projects. Bacterial DNA is routinely discarded when scientists are assembling invertebrate genomes, yet these genes may very well be part of the organism's genome, and might even be responsible for functioning traits.

"It didn't seem possible at first," said Werren, Professor of Biology at the University of Rochester and a world-leading authority on the parasite, called Wolbachia.

"This parasite has implanted itself inside the cells of 70% of the world's invertebrates, co-evolving with them. And now, we've found at least one species where the parasite's entire or nearly entire genome has been absorbed and integrated into the host's. The host's genes actually hold the coding information for a completely separate species."

Wolbachia is considered one of the most prolific parasites in the world, a veritable pandemic for invertebrates. The bacterium invades a member of a species, most often an insect, and eventually makes its way into the host's eggs or sperm. Once there, the Wolbachia is ensured passage to the next generation of its host, and any genetic exchanges between it and the host also are much more likely to be passed on.

To determine how frequently gene exchanges happened between the parasite and the host, the researchers decided to systematically screen invertebrates. Julie Dunning-Hotopp at JCVI found evidence that some of the Wolbachia genes seemed to be fused to the genes of the fruitfly, Drosophila ananassae, as if they were part of the same genome.

Michael Clark, a research associate at Rochester, then fed the flies a simple antibiotic, to kill off the Wolbachia and isolate the fly's genome from that of the parasite's. To confirm the ananassae flies were indeed cured of the bacteria, Clark tested a few samples of DNA for the presence of several Wolbachia genes.

To his dismay, he found them.

"For several months, I thought I was just failing," said Clark. "I kept administering antibiotics, but every single Wolbachia gene I tested for was still there. I started thinking maybe the strain had grown antibiotic resistance. After months of this I finally went back and looked at the tissue again and there was no Wolbachia there at all."

Clark had cured the fly of the parasite, but a copy of the parasite's genome was still present in the fly's genome. He was able to determine that Wolbachia genes were present on the second chromosome of the insect.

Clark confirmed that the Wolbachia genes are inherited like "normal' insect genes in the chromosomes, and Dunning-Hotopp showed that some of the genes are "transcribed' in uninfected flies, meaning that copies of the gene sequence are made in cells that could be used to make Wolbachia proteins.

Werren believes the gene insertions are as a consequence of cells routinely repairing their damaged DNA. As cells go about their regular business, they can accidentally absorb bits of DNA into their nuclei, often sewing those foreign genes into their own DNA. But integrating an entire genome was definitely an unexpected find.

The team is now looking further into the huge insert found in the fruitfly, and whether it is providing a benefit.

"The chance that a chunk of DNA of this magnitude is totally neutral, I think, is pretty small, so the implication is that it has imparted some selective advantage to the host," said Werren.

"The question is, are these foreign genes providing new functions for the host? This is something we need to figure out."

While evolutionary biologists will certainly take note of this discovery, scientists conducting genome-sequencing projects around the world will also have to readjust their thinking.

Before this study, geneticists knew of examples where genes from a parasite had crossed into the host, but such an event was considered a rare anomaly except in very simple organisms. Bacterial DNA is very conspicuous in its structure, so if scientists came across bacterial DNA when sequencing more complex genomes, they would likely discard it assuming it to be merely contamination — perhaps a bit of bacteria in the gut of the animal, or on its skin.

But those genes may not be contamination. They may very well be in the host's own genome. This is exactly what happened with the original sequencing of the genome of the ananassae fruitfly — the huge Wolbachia insert was discarded from the final assembly, despite the fact that it is part of the fly's genome.

In the early days of the Human Genome Project, some studies appeared to show bacterial DNA residing in our own genome, but those were shown indeed to be caused by contamination. Wolbachia is not known to infect any vertebrates such as humans.

"Such transfers have happened before in the distant past," said Werren. "In our very own cells and those of nearly all plants and animals are mitochondria, special structures responsible for generating most of our cells' supply of chemical energy. These were once bacteria that lived inside cells, much like Wolbachia does today.

"Mitochondria still retain their own, albeit tiny, DNA, and most of the genes moved into the nucleus in the very distant past. Like wolbachia, they have passively exchanged DNA with their host cells. It's possible wolbachia may follow in the path of mitochondria, eventually becoming a necessary and useful part of a cell.

"In a way, wolbachia could be the next mitochondria," said Werren. "A hundred million years from now, everyone may have a wolbachia organelle."