August 31, 2007

Life and Awe: The Goosebumps are in the Details

Every so often, some plucky researcher out there in the world of science discovers something that provides me with a goosebumps moment. It's often someone who isn't well-known and it frequently happens by accident. Such a moment occurred when I heard about a discovery made by a research associate named Michael Clark at the University of Rochester. He and principle investigator Jack Werren discovered that the bacterium Wolbachia has found a great way of passing along its genome while allowing a multicellular organism — an insect — to do much of the work of reproduction.

Lateral gene transference, the passing of genetic material from one living thing to another, unrelated species, is not unknown. There's extremely good evidence that it occurred in the deep evolutionary past; both the chloroplasts in photosynthetic plants and the mitochondria found in the cells of most living things almost certainly started out as free-living organisms themselves. The ancestors of todays chloroplasts were on the same branches of the tree of life as cyanobacteria and mitochondria are descended from a simple bacterium related to the one that causes ricketts. Both organelles still contain their own DNA, remnants of the genomes of their ancestral, free-living progenitors. These were incorporated into eukaryotes when life hadn't yet evolved beyond the complexity of single-celled organisms and ever since they've been with us, evolving as we evolve.

We also see lateral gene transference with viruses. Much of what we think of as our own uniquely human DNA isn't really human DNA at all. Viruses reproduce by inserting their genomes into those of other organisms, hijacking the replicative machinery to produce copies of themselves thereafter. It's an extremely effective means of insuring that their genes are preserved for all time. Every living thing on earth carries bits of DNA from both viruses that infected them directly and from those that infected their ancestors. One of the ways we can chart evolutionary history, in fact, is by looking at viral DNA still present in the genetic material of various related organisms because when one species splits into two, both descendants bring the stuff along for the ride. If we look at any pair of species, we can see whether they split before or after their ancestors were first infected by a given virus, and so it's possible to build up a mosaic of such data for use as a measurement of relatedness through time. Every one of us carries a fossil record around with us in the very cells of our bodies. To me, that's fascinating stuff.

We haven't seen bacteria before, as far as I know, that insert their genomes into multicellular organisms, however. As far as has been known, such machinations had long been a province exclusively of viruses. Clark and Werren's discovery, however, changes that hypothesis and opens up the possibility that there's a whole piece of the story of how life evolves that we'd been overlooking until now. It stands to become one of the most important discoveries in biology in the last 30 years, I think, and perhaps more than that. We'll see where it goes, but in the meantime:

One species' entire genome discovered inside another's

Whole-genome transfer raises questions about evolution, sequencing

Scientists at the University of Rochester and the J. Craig Venter Institute have discovered a copy of the entire genome of a bacterial parasite residing inside the genome of its host species.

The finding, reported in today’s Science, suggests 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, posing dramatic implications for evolution.

Such large-scale heritable gene transfers may allow species to acquire new genes and functions extremely quickly, says Jack Werren, a principle investigator of the study.

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,” says 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 percent of the world’s invertebrates, coevolving 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 may be the most prolific parasite in the world—a “pandemic,” as Werren calls it. 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.

Since Wolbachia typically live within the reproductive organs of their hosts, Werren reasoned that gene exchanges between the two would frequently pass on to subsequent generations. Based on this and an earlier discovery of a Wolbachia gene in a beetle by the Fukatsu team at the University of Tokyo, Japan, the researchers in Werren’s lab and collaborators at J. Craig Venter Institute (JCVI) 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 brought a colony of ananassae into Werren’s lab to look into the mystery. To isolate the fly’s genome from the parasite’s, Clark fed the flies a simple antibiotic, killing the Wolbachia. To confirm the ananassae flies were indeed cured of the wolbachia, 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,” says 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. Clark was able to see 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 doesn’t believe that the Wolbachia “intentionally” insert their genes into the hosts. Rather, it is 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.

Werren and Clark are 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 of some selective advantage to the host,” says Werren. “The question is, are these foreign genes providing new functions for the host" This is something we need to figure out..."

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 sequencing a nematode genome, for example, come across bacterial DNA, they would likely discard it, reasonably assuming that it was merely contamination—perhaps a bit of bacteria in the gut of the animal, or on its skin...
Amazing stuff here, and knowledge that may set in motion a true shift in the way we look at life and its changes over time. Not that I think any of them will ever see this, but I congratulate those involved with this work and thank them for this discovery — and for the little thrill I've just had from reading about this. What a great way to start off the morning; I hadn't even finished my coffee yet!

Sphere: Related Content