The gene that causes cystic fibrosis may persist in human populations because, although two copies of it kill, having just one copy protects against tuberculosis, researchers say.

Researchers at Yale University in Connecticut, US, posed the question: why do people get cystic fibrosis? The lethal disease strikes people with mutations in both copies of a particular gene. Historically, such people died before reproductive age – so the mutant genes would be expected to have gradually died out.

Instead the genes have persisted for thousands of years, especially in people of European descent, of whom the disease strikes one in 3000, and 2% of people carry one mutant gene. Other racial groups have a far lower incidence.

So Europeans must have derived some advantage from one copy of the gene that made up for losing the people with two copies – possibly protection from disease, the researchers reasoned. Sickle cell anaemia is an example of such a disease that persists with high incidence in Africans, since having one copy of the gene protects against malaria.


Historical data

Previous studies into the potential benefit of a single cystic fibrosis (CF) mutation focused on cholera or typhoid, because these diseases involve the protein that is mutated in CF, but little evidence had been found.

In the new study, Eric Poolman and Alison Galvani have plugged data from historical death rates for cholera, typhoid and tuberculosis (TB) into a complex demographic model.

Cholera and typhoid simply did not kill enough people to explain the CF gene’s persistence, they found. Even if one CF gene gave total protection against either disease, this would not be enough selective advantage to push the gene to modern European levels.

Unparalleled epidemic

However, between 1600 and 1900, TB caused 20% of all deaths in Europe, an epidemic unparalleled elsewhere. The model showed that even if it gave only partial protection against TB, the CF gene would easily have reached its current levels in Europeans.

“The stage was set (in Europe) by the long-term presence of tuberculosis, which allowed CF mutations to establish themselves, albeit at some lower level. But then the TB pandemic starting in the seventeenth century allowed CF to really take off.” says Poolman.

By contrast, TB only became a major cause of death in India after 1800 – in which time a protective effect would give CF its modern incidence in India, of about one person in 40,000.

Global resurgence

CF patients and carriers of the gene have some resistance to TB. This could be because TB bacteria need a nutrient that CF patients do not make, Poolman and Galvani suggest.

The team calculates that CF rates will gradually fall where TB is controlled, although only at a rate of 0.1% per year.

But lack of adequate control has led to a global resurgence in TB. This week the World Health Organization warned that a “virtually untreatable”, extremely drug-resistant TB has spread worldwide, in some places accounting for one-fifth of new cases.

Journal reference: Journal of the Royal Society Interface (DOI:10.1098/rsif.2006.0154)