In the first evidence that natural selection favors an individual's infection tolerance, researchers from Princeton University in the U.S. and the University of Edinburgh in the U.K. have found that an animal's ability to endure an internal parasite strongly influences its reproductive success. Reported in the journal PLoS Biology, the finding could provide the groundwork for boosting the resilience of humans and livestock to infection, an announcement from Princeton said.
The researchers used 25 years of data on a population of wild sheep living on an island in northwest Scotland to assess the evolutionary importance of infection tolerance. They first examined the relationship between each sheep's bodyweight and its level of infection with nematodes, parasitic worms that thrive in the gastrointestinal tract of sheep. The level of infection was determined by the number of nematode eggs per gram of the animal's feces.
While all of the animals lost weight as a result of nematode infection, the degree of weight loss varied widely: an adult female sheep with the maximum egg count of 2,000 eggs per gram of feces might lose as little as 2% or as much as 20% of her bodyweight, the announcement said. The researchers then tracked the number of offspring produced by each of nearly 2,500 sheep and found that sheep with the highest tolerance to nematode infection produced the most offspring, while sheep with lower parasite tolerance left fewer descendants.
To measure individual differences in parasite tolerance, the researchers used statistical methods that could be extended to studies of disease epidemiology in humans, said senior author Andrea Graham, an assistant professor of ecology and evolutionary biology at Princeton. Medical researchers have long understood that people with similar levels of parasite infection can experience very different symptoms. However, biologists are just beginning to appreciate the evolutionary importance of this individual variation.
Graham and her colleagues used the wealth of information collected over many years on the Soay sheep living on the island of Hirta, about 100 miles west of Scotland's mainland. These sheep provide a unique opportunity to study the effects of parasites, weather, vegetation changes and other factors on a population of wild animals. Brought to the island by people about 4,000 years ago, the sheep have run wild since the last permanent human inhabitants left Hirta in 1930. By keeping a detailed pedigree, the researchers of the St. Kilda Soay Sheep Project can trace any individual's ancestry back to the beginning of the project in 1985, and, conversely, can count the number of descendants left by each individual.
"This island is way out in the North Atlantic, where the sun doesn't shine much," she said. "So tolerant individuals might be the ones who are better able to compete for food or better able to assimilate protein and other useful nutrients from the limited forage."
Tolerant animals might invest energy in gut repair, but would then be expected to incur costs. Graham and her colleagues identified a similar evolutionary tradeoff in a 2010 study that compared immune-response levels and reproductive success in female Soay sheep. They found that animals with strong antibody responses produced fewer offspring each year, but also lived longer. The team has not yet been able to detect costs of parasite tolerance in the sheep, but such costs could help explain variation in tolerance if the most-tolerant animals were at a disadvantage under particular conditions.
While the PLoS Biology findings provide strong evidence that natural selection favors infection tolerance, they do raise questions, such as how the tolerance is generated and why variation might persist from one generation to the next despite the reproductive advantage of tolerance, Graham said. The data in this study did not permit the researchers to detect a genetic component to tolerance. If genetics do play a role, she suspects multiple genes may interact with environmental factors to determine tolerance; ongoing research will help to tease apart these possibilities.
Understanding the genetic underpinnings of nematode tolerance could someday guide efforts to boost tolerance in livestock by identifying and selectively breeding those animals that exhibit a heightened parasite tolerance, said David Schneider, an associate professor of microbiology and immunology at Stanford University.
In people and domesticated animals, intestinal parasites are becoming increasingly resistant to the drugs used to treat infections, Graham said.