Multi-Host Evolution of Avian Malaria in the Wild – EVOMALWILD

In recent years, the emergence or re-emergence of animal and human infectious diseases has been increasingly documented around the world. Ecosystem alterations, and movements of infected people and animals, provide new opportunities for host-parasite mixing, and can drive the introduction of both known and novel parasite genotypes to previously unaffected hosts. Understanding the evolution of multi-host pathogens is therefore essential to predict and ultimately prevent the evolutionary emergence of new infectious diseases.

Malaria parasites infecting not only humans, but also hundreds of other terrestrial vertebrate species, including mammals, reptiles and birds. The similarity of their respective life cycles, plus the generalist nature of many of their dipteran vectors, favours frequent host switches between species. Understanding how Plasmodium species have evolved contrasting exploitation strategies in different vertebrate hosts is therefore key to unravel the evolution and the epidemiology of this disease.

The epidemiology and evolution of multi-host pathogens has attracted a lot of theoretical interest, but studies that combine empirical work in the field, with experimental work in the laboratory are sorely lacking, largely due to the lack of a suitable model system. We propose to use avian Plasmodium, one of the most diverse and abundant vertebrate malarias in nature, to study the genetic and phenotypic diversity underlying multi-host dynamics both in the wild and in controlled laboratory experiments. This work will contrast the dynamics of specialist and generalist Plasmodium lineages to understand and predict the epidemiology and evolution of avian malaria. Three complementary approaches will be developed during this project:

TASK 1 - We will monitor changes in genetic diversity of avian malaria infections across space and time in the wild (i) in several different wild bird species and (ii) in their main mosquito vectors. We will develop a multi-strain, multi-host epidemiological model, which will provide a theoretical framework to infer time-dependent fitness measures for each of the malaria lineages monitored in our study sites.
TASK 2 - We will characterize the phenotypic diversity (virulence and transmission) of different Plasmodium lineages in multiple hosts. Carefully controlled laboratory experiments will allow us to quantify the genetic variance-covariance matrix of malaria phenotypes among multiple hosts. We will investigate within-host competition between different Plasmodium lineages in birds and in mosquitoes. This will allow us to evaluate the genetic constraints acting on malaria evolution in different hosts.
TASK 3 – We will obtain whole genome sequences of the avian Plasmodium lineages circulating in multiple hosts. This will allow us to reconstruct historical population size of these different lineages but also to explore the genomic basis of avian Plasmodium adaptations to multiple host species. In addition, we will carry out the transcriptomic analysis of several Plasmodium lineages in different hosts, focusing, in particular on genes involved in erythrocyte invasion that have been linked to host specificity in human malaria.

Understanding the evolutionary dynamics of Plasmodium in multiple hosts is an essential step towards the development of sustainable control strategies against malaria. This project provides a unique opportunity to combine empirical, experimental, genomic and transcriptomic approaches to monitor, to model and ultimately to predict the dynamics of malaria in the wild.