How viruses played a role in human evolution.

The constant battle between pathogens and their hosts
has long been recognized as a key driver of evolution,
but until now scientists have not had the tools to look
at these patterns globally across species and genomes.
In a new study, researchers apply big-data analysis to
reveal the full extent of viruses' impact on the evolution
of humans and other mammals.
Their findings suggest an astonishing 30 percent of all protein
adaptations since humans' divergence with chimpanzees have been
driven by viruses.
"When you have a pandemic or an epidemic at some point in
evolution, the population that is targeted by the virus either
adapts, or goes extinct. We knew that, but what really
surprised us is the strength and clarity of the pattern we
found," said David Enard, Ph.D., a postdoctoral fellow at
Stanford University and the study's first author. "This is the
first time that viruses have been shown to have such a strong
impact on adaptation."
The study was recently published in the journal eLife and will
be presented at The Allied Genetics Conference, a meeting hosted
by the Genetics Society of America, on July 14.
Proteins perform a vast array of functions that keep our cells
ticking. By revealing how small tweaks in protein shape and
composition have helped humans and other mammals respond to
viruses, the study could help researchers find new therapeutic
leads against today's viral threats.
"We're learning which parts of the cell have been used to fight
viruses in the past, presumably without detrimental effects on
the organism," said the study's senior author, Dmitri Petrov,
Ph.D., Michelle and Kevin Douglas Professor of Biology and
Associate Chair of the Biology Department at Stanford. "That
should give us an insight on the pressure points and help us find
proteins to investigate for new therapies."
Previous research on the interactions between viruses and proteins
has focused almost exclusively on individual proteins that are
directly involved in the immune response -- the most logical place
you would expect to find adaptations driven by viruses. This is
the first study to take a global look at all types of proteins.
"The big advancement here is that it's not only very specialized
immune proteins that adapt against viruses," said Enard.
"Pretty much any type of protein that comes into contact with
viruses can participate in the adaptation against viruses. It turns
out that there is at least as much adaptation outside of the
immune response as within it."
The team's first step was to identify all the proteins that are
known to physically interact with viruses. After painstakingly
reviewing tens of thousands of scientific abstracts, Enard culled
the list to about 1,300 proteins of interest. His next step was
to build big-data algorithms to scour genomic databases and
compare the evolution of virus-interacting proteins to that of
other proteins.
The results revealed that adaptations have occurred three times as
frequently in virus-interacting proteins compared with other
proteins.
"We're all interested in how it is that we and other organisms
have evolved, and in the pressures that made us what we are,"
said Petrov. "The discovery that this constant battle with
viruses has shaped us in every aspect -- not just the few
proteins that fight infections, but everything -- is profound. All
organisms have been living with viruses for billions of years;
this work shows that those interactions have affected every part
of the cell."
Viruses hijack nearly every function of a host organism's cells in
order to replicate and spread, so it makes sense that they would
drive the evolution of the cellular machinery to a greater extent
than other evolutionary pressures such as predation or
environmental conditions. The study sheds light on some
longstanding biological mysteries, such as why closely-related
species have evolved different machinery to perform identical
cellular functions, like DNA replication or the production of
membranes. Researchers previously did not know what
evolutionary force could have caused such changes. "This paper is
the first with data that is large enough and clean enough to
explain a lot of these puzzles in one fell swoop," said Petrov.
The team is now using the findings to dig deeper into past viral
epidemics, hoping for insights to help fight disease today. For
example, HIV-like viruses have swept through the populations
of our ancestors as well as other animal species at multiple
points throughout evolutionary history. Looking at the effects of
such viruses on specific populations could yield a new
understanding of our constant war with viruses -- and how we
might win the next big battle.
Credit:genetics society of America.