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Cow by Daniel Schwen; Horned viper by Mircea Nita

How a quarter of the cow genome came from snakes

Genomes are often described as recipe books for living things. If that’s the case, many of them badly need an editor. For example, around half of the human genome is made up of bits of DNA that have copied themselves and jumped around, creating vast tracts of repetitive sequences. The same is true for the cow genome, where one particular piece of DNA, known as BovB, has run amok. It’s there in its thousands. Around a quarter of a cow’s DNA is made of BovB sequences or their descendants.

BovB isn’t restricted to cows. If you look for it in other animals, as Ali Morton Walsh from the University of Adelaide did, you’ll find it in elephants, horses, and platypuses. It lurks among the DNA of skinks and geckos, pythons and seasnakes. It’s there in purple sea urchin, the silkworm and the zebrafish.

The obvious interpretation is that BovB was present in the ancestor of all of these animals, and stayed in their genomes as they diversified. If that’s the case, then closely related species should have more similar versions of BovB. The cow version should be very similar to that in sheep, slightly less similar to those in elephants and platypuses, and much less similar to those in snakes and lizards.

But not so. If you draw BovB’s family tree, it looks like you’ve entered a bizarre parallel universe where cows are more closely related to snakes than to elephants, and where one gecko is more closely related to horses than to other lizards.

This is because BovB isn’t neatly passed down from parent to offspring, as most pieces of animal DNA are. This jumping gene not only hops around genomes, but between them.

This type of “horizontal gene transfer” (HGT) is an everyday event for bacteria, which can quickly pick up important abilities from each other by swapping DNA. Such trades are supposedly much rarer among more complex living things, but every passing year brings new examples of HGT among animals. For example, in 2008, Cedric Feschotte (now at the University of Utah) discovered a group of sequences that have jumped between several mammals, an anole lizard, and a frog. He called them Space Invaders.

The Space Invaders belong to a group of jumping genes called DNA transposons. They jump around by cutting themselves out of their surrounding DNA, and pasting themselves in somewhere new. They’re also relatively rare—they make up just 2 to 3 percent of our genome. BovB belongs to a different class of jumping genes called retrotransposons. They move through a copy-and-paste system rather than a cut-and-paste one, so that every jump produces in a new copy of the gene. For that reason, they spread like wildfire.

BovB was first discovered in the genomes of cows and other cud-chewing mammals in the 1980s, and seemed to be a signature of that group. Then, in the 1990s, Dusan Kordis and Franc Gubensek detected an extremely similar version of BovB amid the genes of the horned viper. It looked like this piece of DNA had jumped between species. Now, with complete genomes of the cow and other animals at hand, Walsh has more fully mapped BovB’s voyage through the animal kingdom.

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A family tree of BovB sequences

Early on during its travels, BovB split into two major lineages. One group has made its way between a single lizard – the Lord Howe Island gecko –and the horse, the egg-laying platypus and echidna from Australia, and African mammals like the elephant and hyrax. The other group started off in lizards and snakes, and jumped from there into ruminants like cows and sheep, and marsupials like possums and wallabies.

To make sure that their results were real, the team took care to avoid contaminating samples from one animal with the DNA of another. Several different laboratories were involved, and no single one of them was responsible for collecting or processing all the samples. And if contaminated samples were producing phantom sightings of BovB, there’s no reason why those sightings would cluster in particular groups, like lizards or marsupials.

To the team, the best explanation for these bizarre patterns is that BovB jumped between species, and it must have done so at least 9 times during its history—far more than the one or two jumps that other scientists had envisaged.

How did it manage? Walsh found a huge clue when she discovered BovB in the genomes of two tick species, both of which suck the blood of lizards and snakes. Other related ticks bite mammals too, so it’s possible that by biting their way through the animal kingdom, these bloodsuckers inoculated fresh branches of the tree of life with jumping genes.

Many scientists who work in this field have suggested that parasites, including worms, bugs, and viruses, could act as vehicles for hitchhiking genes. Indeed, in their very first paper on the BovB, Kordis and Gubensek said that ticks might be spreading the gene between animals. “It’s a scenario that remains hard to prove, but [Walsh’s] data are as close to a smoking gun as can be in the field,” says Feschotte.

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A tick, by the CDC. Not quite the same species as the one that Walsh identified, but closely related.

Once it lands in a fresh genome, BovB’s ability to spread throughout its new home seems to vary greatly from one animal to another. Between 10 and 11 percent of the cow genome consists of BovB,and a further 14 to 15 percent are descendants of this jumping gene. BovB accounts for 15 percent of a sheep’s and 11 percent of an elephant’s, but horses, sea urchins and zebrafish only have a few copies each.  “Some genomes seem to have provided really favourable environments for BovB to take off, such as ruminants, but others have not, such as the horse,” says David Adelson, who led the study. “I don’t yet have a hypothesis to test to explore this.”

“BovB appears to have no function other than its own replication,” says Adelson. In one case, it seems to have been incorporated into a cow gene, but otherwise, these sequences don’t seem to do anything. Nonetheless, they’re often so common that they must have had some influence.

“The inescapable conclusion from this and a plethora of other recent studies is that horizontal DNA transfer has been a powerful engine of animal genome evolution, much like it is in bacteria,” says Feschotte. “The main difference being that while bacteria swap genes, animals swap transposons.” Adelson adds: “Despite public concern over the transfer of genetic material to create genetically modified organisms, it appears that Mother Nature has been quietly shuffling genomes for some time.”

Reference: Walsh, Kortschak, Gardner, Bertozzi & Adelson. 2012. Widespread horizontal transfer of retrotransposons. PNAS http://dx.doi.org/10.1073/pnas.1205856110

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