For what may be the first time, researchers have discovered a virus inside a host with a non-standard nuclear genetic code — one that differs from the standard genetic code that almost all living things use to produce proteins.
“The finding is significant because it shows that these viruses can overcome what appears to be an insurmountable change in the host genome,” said researcher Derek J. Taylor, professor of biological sciences at the University at Buffalo. “So the fact that we haven’t previously seen any viruses in these species with a modified genetic code may not be because the viruses can’t adapt to that shift. It may be that we haven’t looked hard enough.”
The study, titled “Virus-host co-evolution under a modified nuclear genetic code,” was published on March 5 in PeerJ, a peer-reviewed, open-access journal in which all articles are freely available. The article is available at https://peerj.com/articles/50/.
Taylor’s co-authors on the study are UB PhD candidate Matthew Ballinger, former UB postdoctoral researcher Shaun M. Bowman, and UB Professor Jeremy Bruenn, all in UB’s Department of Biological Sciences.
The team of scientists discovered the highly adapted virus — a totivirus — in the yeast species Scheffersomyces segobiensis (a distant relative of human pathogens in the genus Candida).
In most living things, the genetic code comprises 64 elements called codons, most of which instruct the body to produce a certain amino acid, the basic building block of a protein. In S. segobiensis, however, the genetic code has been modified: A codon known as the “C-U-G codon,” which usually stands for the amino acid leucine, stands instead for the amino acid serine (a change that can affect how proteins function).
It had been thought that such a radical change in the genome may help host species evade viruses, which rely on hosts’ genetic machinery to create new viral proteins and replicate.
However, the presence of the totivirus in S. segobiensis shows that viruses may be more nimble than previously thought, able to overcome even this enormous hurdle. Intriguingly, the totivirus the researchers discovered has only one of the C-U-G codons left in its genome, suggesting that it may have purged that sequence as it adapted to the yeast host.
While viruses have previously been shown to infect organelles known as mitochondria with a different genetic code, this appears to be the first time a virus has been found to use the modified nuclear code of a complex, cellular host, Taylor said. Whereas the origins of the mitochondrial viruses remain mysterious, the current study was able to reconstruct the origins of the novel yeast virus.
The research team found a variety of odd and interesting evidence pointing to a history of co-evolution between totiviruses and yeasts with the modified code. For instance, the modified yeasts appeared to have incorporated genetic material from totiviruses into their genomes on at least four occasions. In total, evidence was found of past, or present, viral infection in five lineages of yeasts with a modified genetic code.
In the yeast Scheffersomyces stipitis, the scientists even identified a former totivirus gene that the host is now using to produce a protein.
“It’s a non-retroviral RNA virus gene being kidnapped and expressed as a protein by a cellular host in the absence of a current viral infection” Taylor said. The function of this protein is unknown, but the result is further evidence of the unexpected co-evolution between viruses and hosts with modified nuclear code.