A new computational model suggests that certain mutations that block infection by the most dangerous species of malaria have not become widespread in people because of the parasite's effects on the immune system. Bridget Penman of the University of Warwick, U.K., and Sylvain Gandon of the CNRS and Montpellier University, France, present these findings in the open-access journal PLOS Computational Biology.
Malaria is a potentially lethal, mosquito-borne disease caused by parasites of the Plasmodium genus. Several protective adaptations to malaria have spread widely among humans, such as the sickle-cell mutation. Laboratory experiments suggest that certain other mutations could be highly protective against the most dangerous human-infecting malaria species, Plasmodium falciparum. However, despite being otherwise benign, these mutations have not become widespread.
To help clarify why some protective mutations may remain rare, Penman and colleagues developed a computational model that simulates the epidemiology of malaria infection, as well the evolution of protective mutations. Importantly, the model also incorporates mechanisms of adaptive immunity, in which the immune system "learns" to recognize and attack specific pathogens, such as P. falciparum.
Analysis of the model's predictions suggests that if people rapidly gain adaptive immunity to the severe effects of P. falciparum malaria, mutations capable of blocking P. falciparum infection are unlikely to spread among the population. The fewer the number of infections it takes for people to become immune to the severe effects of malaria, the less likely it is that malaria infection-blocking mutations will arise.
"Understanding why a potential human malaria adaptation has not succeeded could be just as important as understanding those which have succeeded," Penman says. "Our results highlight the need for further detailed genetic studies of populations living in regions impacted by malaria in order to better understand malaria-human interactions."
Ultimately, understanding how humans have adapted to malaria could help open up new avenues for treatment.
In your coverage please use this URL to provide access to the freely available article in PLOS Computational Biology: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1008181
Citation: Penman BS, Gandon S (2020) Adaptive immunity selects against malaria infection blocking mutations. PLoS Comput Biol 16(10): e1008181. https://doi.org/10.1371/journal.pcbi.1008181
Funding: Funding was provided to SG by the Leverhulme Trust (Visiting Profesorship VP2-2016-028) and by the Agence Nationale de la Recherche (ANR-17-CE35-0012). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: No authors have competing interests.
PLoS Computational Biology