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Retroviral Remnants in Sloth Genome Offer Clues to Viral-Mammalian Co-Divergence

NEW YORK (GenomeWeb News) – Retroviral footprints in the two-toed sloth genome hint at co-divergence between these viruses and mammals.

A team of British and Danish researchers used genomic, phylogenetic, and biogeographic analyses to track the evolutionary history of a type of retroviruses called foamy viruses in mammals. They found many foamy virus-like sequences in the genome of the two-toed sloth, Choloepus hoffmanni that they believe go back more than 100 million years. The research, which appears online today in Science, suggests mammals did not start being infected with foamy viruses recently, but co-diverged with these viruses.

"The descendants of foamy viruses that infected ancestral mammals … have persisted in a surprisingly unchanged form until today," senior author Oliver Pybus, a zoology researcher at the University of Oxford, and his co-authors wrote, "supporting the idea that evolutionary constraint can maintain viral genomic conservation over many millions of years despite exceptionally high short-term rates of mutation."

Retroviruses, in general, are RNA viruses that are reverse-transcribed to DNA before being integrated into their host's genome. Because they insert themselves into the genetic code, these viruses can leave traces in the host genome, the researchers explained.

Pybus and his co-workers focused on foamy viruses, which were not previously detected in the viral "fossil records" of mammalian genomes. The team screened as many mammalian genomes as they could get their hands on. But they only found foamy virus insertions in one genome: that of the two-toed sloth.

The team dubbed the viral sequences "sloth endogenous foamy virus," or SloEFV. Their analysis uncovered hundreds of these elements in the two-toed sloth genome, though just 72 of these still had 1,000 or more bases of coding sequences. And the coding regions that remained were rife with stop codons, insertions, deletions, and frame shift mutations.

The SloEFV grouped phylogenetically with modern-day foamy viruses, the team noted. When the researchers came up with a 11,500 or so base consensus genome for SloEFV, they also found that it aligned — and shared characteristic features — with current foamy viruses.

Because the sloth belongs to a basal mammalian group that diverged from other mammals roughly 105 million years ago, the researchers estimate that foamy viruses were present in mammalian ancestors for more than 100 million years.

Based on such findings, the team speculated that mammals and foamy viruses have been co-evolving since the first mammalian species, co-diverging "across an entire geological era."

"Our analysis highlights the role of evolutionary constraint in maintaining viral genome structure and indicates that accessory genes and mammalian mechanisms of innate immunity are the products of macroevolutionary conflict played out over a geological time scale," they wrote.

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