âIf you pick a random species of insect and look inside its cells, thereâs a 40 percent chance that youâll find bacteria called Wolbachia. And if you look at Wolbachia carefully, youâll almost certainly find a virus called WO, lying in wait within its DNA. And if you look at WO carefully, as Seth and Sarah Bordenstein, from Vanderbilt University, have done, youâll find parts of genes that look like they come from animalsâincluding a toxin gene that makes the bite of the black widow spider so deadly.â
âLetâs start with the bacteria. The various strains of Wolbachia are masters at infecting insects, spiders, woodlice, and other arthropods. Since their hosts are the most numerous and diverse animals in the world, Wolbachia must surely be one of the most successful microbes around. Sometimes, it manipulates the sex lives of its hosts, transforming males into females or even killing them outright. Sometimes, it provides benefits like vitamins or resistance to viruses. The latter skill is important to us, since Wolbachiaâs presence can prevent mosquitoes from spreading the viruses behind dengue fever, Zika, yellow fever, and other important diseases.â
âThis master infector gets infected, in turn, by WO. WO is a bacteriophage, or phage for shortâa virus that specializes in infecting bacteria. It can actively make many copies of itself within Wolbachia, eventually bursting out with fatal results. Alternatively, it can insinuate its DNA into Wolbachiaâs genome, literally becoming part of its host. As the bacterium reproduces, it copies its genome and so copies WO.â
âWO can also switch between these two strategies. If two strains of Wolbachia infect the same insect, WO can awaken and violently burst out of one strain, only to infiltrate the other and gently conceal itself. No surprise then that it is present in the vast majority of Wolbachia strainsâa nigh-omnipresent virus lurking in the genome of one of the planetâs most widespread microbes.â
âFor example, the virus contained part of the gene for latrotoxinâthe chemical in black widow spider venom. The toxin punches holes through the cells of victims, causing their innards to leak fatally outwards. âThere hasnât been another case of a latrotoxin being found outside of spiders,â says Seth.â
âItâs possible that the spiders got the latrotoxin gene from the virus, or that the two evolved their copies independently. But by comparing the various versions of latrotoxin, the Bordensteins think that itâs most likely that the virus got the gene from spiders. It certainly had the right opportunity, since Wolbachia, its host microbe, does indeed infect black widows. The phage could have picked up spider DNA directly from the creatureâs own cells. Or Wolbachia could have picked up spider DNA and then transferred it to the phage. Or other as-yet-unidentified viruses and bacteria could have acted as intermediaries.â
âWhatever the route, this is an unprecedented find. Hereâs why. All living things fall into three major groups or âdomainsâ: the bacteria, the microbes weâre most familiar with; the archaea, a more obscure group of microbes; and the eukaryotes, which includes all animals and other visible, many-celled creatures. For viruses, these domains are like Hogwarts housesâeach has its own, and thereâs no crossover. Ebola, Zika, and influenza can lay us low, but they pose no threat to bacteria. Conversely, phages infect bacteria but donât infiltrate the cells of animals or other eukaryotes. This fidelity is reflected in their genes. Viruses that infect eukaryotes can sometimes pick up eukaryotic DNA, but phages do not. That is, except for WO.â
âWhatâs more, it looks like WO has grabbed bits of DNA from various animal genes and merged them into new ones. âViruses do this,â says Sarah. âItâs like a buffet. They take bits from different genes and put them together to form this super gene.ââ
âThe Bordensteins think that these chimeric genes help WO to succeed at its doubly difficult lifestyle. It can use the standard toolkit of phage genes to break out of Wolbachia, but it then finds itself in an animal cell. If it stays, it must contend with the animalâs immune system. If it wants to leave, it has to pierce an animal membrane. âOnce it gets out, it needs some way of cloaking itself, or counterattacking, or evading animal defenses,â says Sarah. Perhaps it does all of that with the help of its eukaryotic acquisitions, which seem to be involved in producing toxins, interacting with the immune system, forcing cells to self-destruct, and other relevant functions.â
âDoes this mean that the phage is actually infecting animal cells? It depends on what you count as infection. âI wouldnât personally go that far,â says Seth, âbut I think you could bend the language that way.â Thatâs certainly how Elizabeth McGraw, a Wolbachia specialist at Monash University, sees it. âItâs the first report of a virus infecting multiple domains of life,â she says. By picking up animal genes, WO has become âa Frankenphage that may be better at infecting animals than its ancestors that contained only phage genes.ââ
âThe phageâs abilities might also be useful to Wolbachia. This bacterium is extraordinarily good at manipulating the sex lives of its hosts, and scientists have identified several potential genes behind its skills. But the Bordensteins have found that some of these manipulation genes arenât part of Wolbachiaâs own genomeâinstead, they belong to WO. The couple are in the process of publishing their results; if theyâre right, then hereâs a bacterium that manipulates animals using animal genes found in a virus.â
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