678 15 FEBRUARY 2019 • VOL 363 ISSUE 6428 sciencemag.org SCIENCE
PHOTO: ROB SUISTED/NATURE’S PIC IMAGESHow rabbits escaped a deadly
virus—at least for now
Same genetic changes found in rabbits on two continents
EVOLUTIONR
esearchers have written another chap-
ter in the textbook case of an arms
race between a host and its pathogen.
The main characters in this 70-year
seesaw drama are the voracious Eu-
ropean rabbit (Oryctolagus cuniculus)
and a virus deliberately released in France
and Australia to kill off the rabbits and
protect fields and pastures. Working with
museum specimens collected decades ago,
a team has discovered that rabbits on two
continents evolved the same genetic changes
to beat back the virus—before the virus itself
changed and regained the upper hand.
The find is a striking example of how evolu-
tion sometimes repeats itself, and it may hold
clues to how human im-
mune systems respond—
or don’t—to pathogens.
The rabbit work, pub-
lished online this week
in Science, “provides key
new information on one
of the greatest stories in
evolution,” says Edward
Holmes, an evolutionary
biologist at the Univer-
sity of Sydney in Aus-
tralia who studies the
biocontrol virus.
In Australia, a few
dozen European rabbits
introduced in the mid-1800s for hunters
did what the animals famously do. They
multiplied until hundreds of millions were
chowing down on crops. So, in 1950, after
a smallpoxlike virus found in South Ameri-
can rabbits turned out to kill the European
relative, Australian authorities released the
virus into the wild, cutting the rabbit popu-
lation by 99%. A few years later, the virus,
called myxoma, was released in France and
eventually spread to the United Kingdom.
The result was “an opportunity to trace
host-pathogen arms races right in front of
our eyes,” says Jia Liu, a biologist at the Uni-
versity of Arkansas for Medical Sciences in
Little Rock. Within a decade, rabbit num-
bers were on the rise again as some evolved
resistance to this deadly infection and the
virus itself became less deadly.
To understand the rabbit’s adaptations,Joel Alves, now an evolutionary biologist
at the University of Oxford in the United
Kingdom, evolutionary geneticist Francis
Jiggins at the University of Cambridge
in the United Kingdom, and colleagues
tracked down specimens of U.K., Australian,
and French O. cuniculus collected by muse-
ums prior to the virus’s introduction. They
sequenced all the genes and other DNA
that might influence the body’s immune
defenses and compared the results with
sequences from modern rabbits living in
the same places. The comparisons revealed
changes in many genes, usually a shift in the
frequency of particular versions, or alleles,
of a gene. Strikingly, half of the changes
were shared by the rabbits in all three
countries—evidence of parallel evolution.
One allele shift affected
the rabbits’ interferon, a
protein released by im-
mune cells that sounds
the alarm about a viral at-
tack and helps trigger an
immune response. Com-
pared with preinfection
rabbits, modern rabbits
make an interferon that
is better at responding to
the biocontrol virus, the
researchers found when
they added different ver-
sions of the protein to
rabbit cell lines.
The virus has not stood still. In 2017,
Holmes and his colleagues reported that in
the 1970s the virus developed a greater ability
to suppress the rabbit’s immune responses.
That change, as well as the natural emer-
gence of another rabbit-killing virus, has
caused populations to decline again. But in
contrast to the parallel evolution in rabbits,
myxoma viruses in the various locations took
different genetic paths to regaining potency.
Andrew Read, an evolutionary micro-
biologist at Pennsylvania State University
in State College, suggests the viral counter-
attack “is a cautionary tale” for researchers
aiming to take charge of the evolutionary
arms race by introducing biocontrol agents
or making crops or livestock more resistant
to disease. “One should be careful about evo-
lution and counterevolution,” he says. “The
rabbit hasn’t won.” jBy Elizabeth PennisiThe European rabbit devastated crops
and pastures in Australia and elsewhere.improved, reaching 79% in 2012 and 2013.
But in 2014, then-President Viktor
Yanukovych was ousted after violent protests,
Russia annexed Crimea, and armed conflict
broke out in eastern Ukraine. Paralyzed,
the government failed to order measles vac-
cine until late 2015. Because of shortages, in
2016, Ukraine vaccinated only 42% of its in-
fants. And that year, just 31% of 6-year-olds
received the recommended second measles
shot—one of the lowest rates in the world.
“If you have a high rate of unvaccinated
children, you will face this kind of outbreak,”
says Vusala Allahverdiyeva, a physician who
is a technical officer in WHO’s Kyiv office.
There are other problems, too. Authori-
ties have grappled with basic challenges.
Investigating an outbreak of 90 cases in
children in a mountainous region in west-
ern Ukraine in 2018, MOH found the chil-
dren had been vaccinated at a clinic that
experienced frequent power outages and
had no generator. (The vaccine must be
stored at less than 8°C to be effective.)
A faulty vaccine may also have played a
role. According to MOH, more than 20,
of those infected in 2018 were adults who
would have been vaccinated decades ago
with a Russian vaccine that was dropped
in 2001. The ministry is trying to identify
whether that vaccine was less effective in
some years, with an eye to revaccinating
those who received it.
MOH has been striving to catch up. It is
now procuring the vaccine more cheaply
through UNICEF; sending mobile vaccina-
tion brigades from school to school in Lviv, a
hard-hit area; and preparing to provide cash
incentives to Ukraine’s underpaid physicians
to vaccinate all children in their practices.
In 2017, the country’s coverage rebounded to
93% of infants and 91% of 6-year-olds.
But because of Ukraine’s large pool of
unvaccinated or undervaccinated people,
the epidemic roars on. “We need to start
thinking outside the box,” Suprun says.
For instance, UNICEF is working with the
government on a campaign urging grand-
parents, who often care for young children
in Ukraine, to get their charges vaccinated.
The Ukrainian outbreak caps a year in
which measles cases surged around the
globe. As of mid-January, WHO had received
reports of more than 229,000 measles cases
in 2018. The global number is expected to
rise by the time it is finalized in June, but
it’s already a 32% increase from 2017.
“The root cause of the measles outbreaks
... is a failure to adequately vaccinate,” says
Katrina Kretsinger, the lead measles ex-
pert at WHO headquarters. “Many people
in many countries remain susceptible, and
large pockets of susceptible persons can
lead to large outbreaks.” j
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