This just in: A key to living a long, healthy life is to avoid getting sick. The observation that worms live longer by avoiding harmful bacteria is not earth-shattering. But the basis of this life-extending behavior turns out to be riveting: A single genetic change in the tiny worm Caenorhabditis elegans compels some worms to stay away from harmful bacteria and others to eat the microorganisms, researchers report online January 15 in Science.
Immunity researcher Dennis Kim and his colleagues noticed that a population of worms recently isolated from their native Hawaiian habitat succumbed to infection much faster than a standard laboratory strain of the worms. Although the two populations are the same species, the worms’ DNA harbor rare differences caused by adaptation to different environments, says Kim, of the Massachusetts Institute of Technology. The disparity in survival could be explained by genetic differences, the researchers reasoned.
The Hawaiian C. elegans have a different version of a gene called npr-1 than do the common lab variety, Kim’s team discovered. The Hawaiian version of the gene — which encodes a protein similar to a human protein that senses signals from neurons — makes less of the protein. Lab C. elegans worms manipulated by scientists to have an npr-1 gene mutation that similarly hinders the protein’s production had the same susceptibility to the pathogenic bacteria as the Hawaiian worms, suggesting that this single gene was responsible for the behavior difference.
Previous studies have shown that npr-1 may have a role in kick-starting the immune system by turning on genes that encode infection-fighting proteins. Lab strain worms produce more npr-1 protein, which may make the worms better at warding off bacterial attacks. But Kim and his group found a different role for npr-1, one that prevents the worms becoming infected in the first place.
When the researchers replaced all the worms’ usually innocuous bacterial grub with a small lawn of harmful bacteria, the Hawaiian worms and the npr-1 mutant lab strain worms both gravitated to and ate the pathogenic bacteria, resulting in a high death rate. In contrast, the nonmutant lab strain worms avoided the bacteria and survived longer.
By marking the bacteria with green fluorescent protein, researchers could measure the amount of bacteria in the worms’ guts. . The guts of the Hawaiian worms and npr-1 mutant lab strain worms glowed bright green under the microscope, while the guts of the nonmutant lab strain worms did not.
Researchers next spread the harmful bacteria all over the worms’ habitat so that the bacteria were unavoidable. In this environment, Hawaiian and all lab strain worms had similar amounts of green bacteria in their guts. Importantly, the survival rate of the three worm populations, which had been different when the worms were able to avoid the bacteria, became indistinguishable.
Equal exposure to pathogens equalized the worms’ death rates. The results suggest that the aversion the nonmutant lab worms show to crawling on bacteria — enabled by the strain’s particular version of the npr-1 gene — is what ensured their survival, rather than the strengths of their immune systems.
The new work “convincingly shows” that npr-1 controls behavior that leads to enhanced survival, comments Jonathan Ewbank, a researcher at the Center of Immunology Marseille-Luminy in France who studies host-pathogen interactions. .
Kim posits that distinct populations of worms may encounter different pressures. Worms face a dilemma when they meet bacteria — to eat or to avoid. “There must be a balance,” says Kim. The risk of eating harmful bacteria that could cause infections in the worms is weighed against the threat of starvation.
Well-fed lab strains can afford to be choosy about what they eat, says Kim. On the other hand, the Hawaiian strain may do better to risk infection, but get a good meal. The new research shows how a naturally occurring mutation in a single gene can cause clear behavioral differences, which ultimately lead to different survival rates.
The npr-1 gene “allows the organism to weigh up the pros and cons of different environments, and presumably, survive,” says Ewbank.
