Hitchhiking virus confirms saga of ancient human migration

October 21, 2013

MADISON, Wis. -- A study of the full genetic code of a common human virus offers a dramatic confirmation of the "out-of-Africa" pattern of human migration, which had previously been documented by anthropologists and studies of the human genome.

The virus under study, herpes simplex virus type 1 (HSV-1), usually causes nothing more severe than cold sores around the mouth, says Curtis Brandt, a professor of medical microbiology and ophthalmology at the University of Wisconsin-Madison. Brandt is senior author of the study, now online in the journal PLOS ONE.

When Brandt and co-authors Aaron Kolb and Cécile Ané compared 31 strains of HSV-1 collected in North America, Europe, Africa and Asia, "the result was fairly stunning," says Brandt.

"The viral strains sort exactly as you would predict based on sequencing of human genomes. We found that all of the African isolates cluster together, all the virus from the Far East, Korea, Japan, China clustered together, all the viruses in Europe and America, with one exception, clustered together," he says.

"What we found follows exactly what the anthropologists have told us, and the molecular geneticists who have analyzed the human genome have told us, about where humans originated and how they spread across the planet."

Geneticists explore how organisms are related by studying changes in the sequence of bases, or "letters" on their genes. From knowledge of how quickly a particular genome changes, they can construct a "family tree" that shows when particular variants had their last common ancestor.

Studies of human genomes have shown that our ancestors emerged from Africa roughly 150,000 to 200,000 years ago, and then spread eastward toward Asia, and westward toward Europe.

Scientists have previously studied herpes simplex virus type 1 by looking at a single gene, or a small cluster of genes, but Brandt notes that this approach can be misleading. "Scientists have come to realize that the relationships you get back from a single gene, or a small set of genes, are not very accurate."

The PLOS ONE study used high-capacity genetic sequencing and advanced bioinformatics to analyze the massive amount of data from the 31 genomes.

The technology of simultaneously comparing the entire genomes of related viruses could also be useful in exploring why certain strains of a virus are so much more lethal than others. In a tiny percentage of cases, for example, HSV-1 can cause a deadly brain infection, Brandt notes.

"We'd like to understand why these few viruses are so dangerous, when the predominant course of herpes is so mild. We believe that a difference in the gene sequence is determining the outcome, and we are interested in sorting this out," he says.

For studies of influenza virus in particular, Brandt says, "people are trying to come up with virulence markers that will enable us to predict what a particular strain of virus will do."

The researchers broke the HSV-1 genome into 26 pieces, made family trees for each piece and then combined each of the trees into one network tree of the whole genome, Brandt says. "Cécile Ané did a great job in coming up with a new way to look at these trees, and identifying the most probable grouping." It was this grouping that paralleled existing analyses of human migration.

The new analysis could even detect some intricacies of migration. Every HSV-1 sample from the United States except one matched the European strains, but one strain that was isolated in Texas looked Asian. "How did we get an Asian-related virus in Texas?" Kolb asks. Either the sample had come from someone who had travelled from the Far East, or it came from a native American whose ancestors had crossed the "land bridge" across the Bering Strait roughly 15,000 years ago.

"We found support for the land bridge hypothesis because the date of divergence from its most recent Asian ancestor was about 15,000 years ago. Brandt says. "The dates match, so we postulate that this was an Amerindian virus."

Herpes simplex virus type 1 was an ideal virus for the study because it is easy to collect, usually not lethal, and able to form lifelong latent infections. Because HSV-1 is spread by close contact, kissing or saliva, it tends to run in families. "You can think of this as a kind of external genome," Brandt says.

Furthermore, HSV-1 is much simpler than the human genome, which cuts the cost of sequencing, yet its genome is much larger than another virus that also has been used for this type of study. Genetics often comes down to a numbers game; larger numbers produce stronger evidence, so a larger genome produces much more detail.

But what really jumped out of the study, Brandt says, "was clear support for the out-of-Africa hypothesis. Our results clearly support the anthropological data, and other genetic data, that explain how humans came from Africa into the Middle East and started to spread from there."

The correspondence with anthropology even extends, as before, to the details. In the virus, as in human genomes, a small human population entered the Middle East from Africa. "There is a population bottleneck between Africa and the rest of the world; very few people were involved in the initial migration from Africa," Brandt says. "When you look at the phylogenetic tree from the virus, it's exactly the same as what the anthropologists have told us."
-end-
The PLOS ONE paper is available at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0076267. These studies were supported by grants from the National Institutes of Health: R01EY07336 and R01EY018597.

--David Tenenbaum, 608-265-8549, djtenenb@wisc.edu

University of Wisconsin-Madison

Related Genome Articles from Brightsurf:

Genome evolution goes digital
Dr. Alan Herbert from InsideOutBio describes ground-breaking research in a paper published online by Royal Society Open Science.

Breakthrough in genome visualization
Kadir Dede and Dr. Enno Ohlebusch at Ulm University in Germany have devised a method for constructing pan-genome subgraphs at different granularities without having to wait hours and days on end for the software to process the entire genome.

Sturgeon genome sequenced
Sturgeons lived on earth already 300 million years ago and yet their external appearance seems to have undergone very little change.

A sea monster's genome
The giant squid is an elusive giant, but its secrets are about to be revealed.

Deciphering the walnut genome
New research could provide a major boost to the state's growing $1.6 billion walnut industry by making it easier to breed walnut trees better equipped to combat the soil-borne pathogens that now plague many of California's 4,800 growers.

Illuminating the genome
Development of a new molecular visualisation method, RNA-guided endonuclease -- in situ labelling (RGEN-ISL) for the CRISPR/Cas9-mediated labelling of genomic sequences in nuclei and chromosomes.

A genome under influence
References form the basis of our comprehension of the world: they enable us to measure the height of our children or the efficiency of a drug.

How a virus destabilizes the genome
New insights into how Kaposi's sarcoma-associated herpesvirus (KSHV) induces genome instability and promotes cell proliferation could lead to the development of novel antiviral therapies for KSHV-associated cancers, according to a study published Sept.

Better genome editing
Reich Group researchers develop a more efficient and precise method of in-cell genome editing.

Unlocking the genome
A team led by Prof. Stein Aerts (VIB-KU Leuven) uncovers how access to relevant DNA regions is orchestrated in epithelial cells.

Read More: Genome News and Genome Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.