Genome Surprise: Guinea Pigs Have Ebola!

By Brandon Keim • July 29, 2010 • 2:28 pm

The ebola virus is one of the nastiest pathogens known to man. It corrodes blood vessels and stops clotting, leaving most of its human victims bleeding to death through their pores. And guinea pigs — along with opossums, wallabies and insect-eating bats — have it in their genes.

A genomic hunt for virus genes traced sequences to Ebola and the closely related Marburg virus in no fewer than six vertebrate species. Echoes of the less-gruesome borna virus family appeared in 13 species, including humans. The genes appear to have been mixed in about 40 million years ago, and have stuck around ever since.

“Some of these sequences have been conserved,” and that’s almost certainly not a coincidence, said cell biologist Ann Marie Skalka of the Fox Chase Cancer Center. “We speculate that some of these must have provided an evolutionary advantage.”

Skalka specializes in RNA viruses, which unlike most common viruses are made from single strands of primitive genetic material, rather than DNA.

Common viruses, better known as retroviruses, insert their DNA into the genomes of infected cells. They hijack its function and, should the cell survive, leave pieces of themselves behind. Retroviral leftovers have accumulated for hundreds of millions of years in animal genomes; they account for about 8 percent of the human.

RNA viruses, however, were long thought to leave no leftovers. They float outside a cell’s chromosomes, hijacking its machinery from afar and ostensibly leaving genomes intact. But that assumption proved wrong.

In 2007, Israeli scientists studying a bee-infecting RNA virus noticed that some colonies were unusually resistant. When they analyzed the bees’ genomes, they found fragmented gene sequences resembling those from the virus. The match wasn’t exact; instead, the fragments seemed to date from some ancestral infection.

The findings spurred Skalka to compare more animal genomes to other RNA virus sequences. She wasn’t alone: While writing the latest paper, published July 29 in Public Library of Science Pathogens, researchers from the University of Texas published a landmark finding of ancient borna virus genes in the human genome.

While those findings stole the thunder from the latest study, Skalka’s work has now expanded the evidence for genomic RNA viral fossils across the animal kingdom. “We were amazed at how many we found,” she said.

Skalka’s team found evidence of 80 ancient RNA viral jumps in 19 of 48 vertebrate genomes, from lampreys to cows and humans. With two exceptions — genes from the little-known Midway virus in zebrafish, and Tamana bat virus genes in a fish called the Medaka — the genes came from borna viruses or filoviruses, a family containing the dread Ebola and Marburg.

In addition to the aforementioned guinea pigs, insect-eating bats, opossums and wallabies, shrews and palm-sized primates called tarsiers contained filovirus fragments. Among the species joining humans in carrying borna virus fragments are cows, lemurs and mice.

How these gene fragments jumped from viruses to vertebrates is a matter of speculation. Skalka suspects that malfunctioning machinery in sperm or egg cells could have copied RNA virus genes, then slipped them into chromosomes later duplicated during reproduction.

Also speculative is what these viral fragments did — or still do, given their conspicuous lack of random mutations that gather in unused genes — for their unwitting recipients.

In the Israeli bees, the RNA virus genes appear to be protective; they may act like a vaccine, or jam invading viruses with almost-but-not-quite-alike proteins. That could also be the case with humans, who are generally resistant to borna virus infection, and other animals flagged by the study.

“You could imagine that the proteins made by these genes would look like the virus proteins, but they’re not exactly the same. And if these funny proteins are there, maybe they muck up the works,” said Skalka, who plans to focus her research on fragments in the human genome. “There would be a real advantage to that.”

According to Ian Lipkin, a genetic epidemiologist at Columbia University, Skalka’s “elegant study” underscores the complicated, species-spanning nature of our bodies.

“The more we delve into genomics the more we become uncertain as to who and what we are,” said Lipkin. “Fragments of retroviruses represent up to 10 percent of the human genome. The number of bacteria on and in our bodies outnumber human cells by 10 to 1. These are not silent passengers.”

Images: 1) An ebola virus particle./University of Waterloo. 2) A phylogenetic tree of vertebrates with approximate dates of borna (circle) and ebola (triangle) virus insertions./PLoS Pathogens.

From: http://www.wired.com/wiredscience/2010/07/ebola-in-genomes/