Scientists Discover Hybrid Virus
Findings point to a virus with genes from RNA and DNA predecessors
1 June 2012 – Portland State University researchers have discovered a virus that may provide clues about the collective origin and evolutionary history of viruses – the most abundant organisms on earth.
The newly discovered virus is a medley of sequences from different types of genetic material representing a previously unknown combination. The genome of this hybrid virus sequence contains genes homologous to both previously identified RNA and DNA viruses. The identification of a hybrid virus sequence indicates that at some point in time, viruses with different types of genetic material were swapping genes.
Researchers from Portland State University traveled to northern California to collect samples from the muddy waters of Boiling Springs Lake (BSL), America’s largest hot spring with a low temperature of 52oC (125oF) and a pH of 2.5, about the same as lemon juice. No herbivores will venture into the lake to take advantage of the microbes living in the water, so the only predators of the purely microbial ecosystem are viruses. One of the microbes native to BSL, Sulfolobus solfataricus, is used in the lab of Dr. Kenneth Stedman, associate professor at Portland State University, as a model organism for eukaryotic DNA replication.
Identifying viruses that infect eukaryotes is of scientific interest because viruses are often used as laboratory tools to perform molecular manipulations of their hosts.
When Geoffrey Diemer, a graduate student in Dr. Stedman’s lab, analyzed the BSL samples for the viruses, he found none known to infect Sulfolobus. Diemer then used a metagenomics approach to genetically identify any and all viruses present. After building complete sequences for some of those vial genomes, Diemer began analyzing the approximately 500,000 sequences.
One of those sequences is from a circular, single-stranded DNA virus. The newly identified virus contains a gene that encodes rolling circle replicase (Rep), a protein involved in DNA replication that is common to viruses with circular genomes. This particular Rep is homologous to the Rep of Circoviridae, a group of DNA based viruses that infect birds and pigs. Additionally, and with no known precedent, Diemer recognized that the newly identified virus also contains a gene homologous to a gene from Tombusviruses that encodes capsid protein, the outer shell of the virion. Tombusviruses are single-stranded RNA viruses that infect plants. Because the newly identified virus possesses gene sequences similar to RNA viruses and DNA viruses, it earned the name Boiling Spring Lake RNA DNA Hybrid Virus, or BSL-RDHV.
Although BSL-RDHV was the first hybrid virus identified, it is not the only one of its kind. When Diemer searched the database of the Global Ocean Survey, or GOS, a program cataloging the genetic sequences of samples obtained from the world’s oceans, he identified three other hybrid sequences that had previously gone unnoticed in the huge database.
“It’s quite straightforward to find a sequence you’re looking for in the GOS database, but if you aren’t searching for something particular, it’s just raw data – no single sequence is going to jump up and say hello unless you’re looking for it. The BSL-RDHV sequence was easy to identify in our dataset because it was so strange and out of place,” Diemer said.
The existence of hybrid viruses in multiple locations, such as BSL and the sites of the GOS, is probably not due to convergent evolution, or reaching the same endpoint from different starting points. “The most likely scenario is that the hybridization of the DNA and RNA viruses occurred millions of years ago, which isn’t all that long on an evolutionary time-scale, and that the virus has since diverged in different environments,” Diemer said.
The evolution of viruses has been a troublesome area of study for researchers due to the frequency of gene swapping that occurs between different viruses. When viruses replicate inside the cells of their hosts, they sometimes pick up bits of their host’s genome and other times leave bits of their own genome. Those bits are maintained in future generations of both viruses and hosts. Eventually, other viruses will infect the same host, and may pick up genes left behind by other viruses. Alternatively, two viruses may infect the same host simultaneously and during replication of their genomes, they may pick up bits of each other’s genetic material.
However, all that swapping of genetic material was predicted to only occur between viruses that shared the same type of genetic material – either RNA or DNA. BSL-RDHV and the three GOS sequences indicate that prediction was inaccurate, highlighting the value of basic research endeavors such as Diemer’s. Evolutionary analysis indicates the simplest way RNA-based genes could have entered a DNA-based virus is likely the alternate method of swapping – that the viruses were able to infect the same cell at the same time and somehow their genomes were transcribed, recombined, and packaged into a single new viral particle.
Since both Circoviridae and Tombusviruses infect eukaryotic hosts, Stedman suspects BSL-RDHV also infects a eukaryotic host. “Trying to find the host is going to be a major focus for the future. Having that host-virus pair is really crucial, otherwise all we have is a sequence,” Stedman said.
Future studies involving BSL-RDHV may lead to greater characterization of viral evolution, more detailed understanding of the dynamics of the BSL ecosystem, and potentially tools for research into how DNA replicates.
The full report of BSL-RDHV’s discovery, “A novel virus genome discovered in an extreme environment suggests recombination between unrelated groups of RNA and DNA viruses” is published online in the 19 April 2012 issue of Biology Direct.