Part Human, Part Virus

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A lot of people think of viruses and bacteria in our bodies as nothing more than pests. It’s certainly true that a lot of them do an excellent job of making us ill. But some viruses and bacteria merged with our ancestors over the course of billions of years, and if you were to have them removed from your body today, you’d die faster than if you’d gotten a massive dose of Ebola.

In order to breathe, we depend on sausage-shaped blobs in our cells called mitochondria. When I say we, I mean not just humans or animals, but a vast group of species known as eukaryotes, which also includes plants, fungi, algae, slime molds, and various amoeba-like creatures. Mitochondria use oxygen and other chemicals to create the fuel our cells use. When mitochondria were first discovered at the end of the 1800s, many scientists were struck by how much they looked like bacteria. Some even went so far as to say that they were bacteria–that somehow every cell in our body was invaded by oxygen-breathing microbes, providing them shelter in exchange for fuel.

Scientists already knew that other bacteria could live inside animals or plants. Some bacteria live inside cows, where they digest the tough tissues of the grass their hosts eat; the cows then eat some of the bacteria. Still, it was one thing to say that bacteria lived inside our bodies, and another to say that they lived inside our cells.

But meanwhile more bacteria-like things were turning up inside cells. Plants, for example, have a second set of blobs in their cells that they use to carry out photosynthesis. Known as chloroplasts, they capture incoming sunlight and use its energy to combine water and carbon dioxide into organic matter. And like mitochondria, chloroplasts bear a striking resemblance to bacteria. Some scientists became convinced that chloroplasts were, like mitochondria, a form of symbiotic bacteria–specifically, that they descended from cyanobacteria, the light-harnessing microbes that live in oceans and fresh water.

Until the early 1960s, the symbiotic theory sputtered in and out of the scientific fashion like a weak flame. But in the 1960s, scientists discovered that mitochondria and chloroplasts have genes of their own. They use their DNA to make their own proteins, and when they duplicate themselves, they make extra copies of their DNA, just as bacteria do. Yet scientists still lacked the tools for finding out exactly what sort of DNA mitochondria and chloroplasts carried. Skeptics suggested their genes had originated inside the nucleus, and at some point evolution had moved it into outlying shelters.

But in the mid-1970s two teams of microbiologists, one headed by Carl Woese of the University of Illinois, and the other by W. Ford Doolittle at Dalhousie University in Nova Scotia, showed that this was not so. They studied the genes inside the chloroplasts of some species of algae, and they found that they bore little resemblance to the genes in the algae’s nucleus. Chloroplast DNA, it turns out, is cyanobacteria DNA. In the late 1970s Doolittle’s team showed that mitochondria were also bacterial genes, and in the years that followed, other scientists zeroed in on exactly which kind of bacteria they belonged to. In 1998, Siv Andersson of Upsalla University in Sweden and her colleagues discovered the closest relative of mitochondria yet known: Rickettsia prowazekii, a vicious bacteria that causes typhus.

At some point in the distant past, the evidence now indicates, a long-lost oxygen-breathing bacterium gave rise to the ancestors of both Rickettsia and mitochondria. Both lineages were originally free-living microbes, feeding on the nutrients that surrounded them. At some point, each lineage began to live inside other organisms. The ancestors of Rickettsia evolved into a ruthless parasite that could plunge into its hosts and ravage them. But the bacteria that invaded our ancestors ended up in a kinder relationship. Proto-mitochondria may have hung around early eukaryotes to feed on their wastes, and the eukaryotes–which could not use oxygen for their metabolism–came to rely in turn on the wastes of the oxygen-breathing proto-mitochondria. Eventually the two species merged together, and the exchanges between them began to take place with a single cell.

Over time, mitochondria lost a lot of their genes. Although they had once been essential for the free-living ancestors of mitochondria, they now were useless, since their hosts could already take care of a lot of the work involved in staying alive. When these genes were accidentally cut out of the mitochondrial genome by a mutation, the mitochondria (and their hosts) did not suffer. Many other genes became incorporated into the DNA in the nucleus of eukaryotes. Even after these single-celled eukaryotes evolved into much more complex species–oak trees, truffles, people–mitochondria continued to play their essential role. (I go into more detail on all this in my book Evolution.)

The story does not stop here, though. Jonathan Filee and Patrick Forterre, two French biologists, have a paper in press in Trends in Microbiology reporting on some surprising results from their new studies of mitochondrial DNA. Some of the surviving genes in mitochondria produce enzymes whose job it is to build new mitochondrial DNA, as well as RNA, a single-stranded version of DNA that acts as a genetic messenger among other jobs. Unlike the rest of the genes in mitochondria, these DNA and RNA-building genes don’t resemble the corresponding genes of related bacteria. They are genes from viruses.

How did viruses contribute genes that are now essential for our survival? Filee and Forterre searched for the most closely related version of the virus genes in mitochondria. They found that the genes resembled DNA and RNA building genes from a large family of bacteria-infecting viruses called bacteriophages T3/T7. This was a surprising result at first, because T3/T7 viruses that were known at the time were a nasty bunch of parasites that invade bacteria, making a lot of new copies of themselves with the help of their of their hosts’ cellular machinery, and then explode out of the bacteria, leaving them to die.

But a continued search brought another surprise. The scientists found the genomes of some T3/T7 viruses stitched into the DNA of some free-living bacteria. So-called “cryptic” viruses are pretty common, and it’s likely that they are the result of defective genes that failed to make new copies of them. The invading virus’s DNA simply became a harmless part of its host’s genome. In many cases, the genes of cryptic viruses have suffered major damage from later mutations and many of their genes have been cut out of their host genomes altogether. But a few remnants still survive, and they’re enough to allow Filee and Forterre to get some clues to the origin of the virus genes in our own mitochondria.

Here’s the history as they now see it: the free-living, oxygen-breathing ancestors of mitochondria were infected with some nasty T3/T7 viruses. Most of the time the viruses were fatal. But some mutant tried to replicate itself inside a proto-mitochondrion and failed. Its genes were trapped in the genome of its host. Its host was able to reproduce, and one of its descendants took up residence inside the cell of a eukaryote. At some point after this merger, a mutation caused the virus’s DNA and RNA copying genes to come back online. They took over the job of making these molecules, and the mitochondria’s own genes for this job were later stripped out of its genome.

It’s a plausible hypothesis for a number of reasons. Filee and Forterre didn’t just pull the notion that viral genes can become active again out of a hat; this sort of viral resurrection has been documented in other species. Not only is the hypothesis plausible, but it’s a tantalizing as well. It suggests that we are chimeras built from the DNA of eukaryotes, bacteria, and viruses, all mixed together through a natural version of genetic engineering. Forterre even argues that these sorts of results are going to turn out to be the tip of the iceberg. Like many scientists, he believes that before life was based on DNA, the Earth was inhabited by RNA-based life. He argues that DNA was an invention of viruses of these RNA-based organisms, which the RNA-based organisms then seized for their own use. All this may not make you any fonder of the chickenpox you may have had as a kid, but it may at least give you a feeling of kinship.