Do breakout haplotypes drive parasitemia spikes in avian malaria?

Abstract During an infection, the genetic composition of the pathogen population in the host might range from clonal to genetically diverse, depending on the genetic variation of the inoculum, mutation events, genetic drift, and host selection during the course of the infection. Variation in the genetic diversity of avian malaria parasites, both within and between individual hosts, is not well documented. To shed light on this, we used avian malaria to investigate how changes in the predominant haplotype varied between infection events and also within single infections over time. This was done by experimentally inoculating nine birds with the blood of one bird infected with Plasmodium relictum (lineage SGS1), and sequencing 1.03 Mb (13%) of the parasite exome before and after peak infection. In each infected bird, different haplotypes became established and changed in relative frequency over time. Several birds did not effectively suppress parasitemia, and we identified exclusive non-synonymous SNPs in gene families with functions related to immune evasion and host cell invasion in those infections, suggesting that some haplotypes might be harder for some individual hosts to suppress than others. We speculate that these haplotypes existed at low relative frequencies in the donor bird, but only increased in frequency (i.e., became runaway haplotypes) in a subset of susceptible host individuals. Alternatively, those SNPs might represent novel mutations that appeared independently in only a subset of host individuals. Deeper sequencing of the initial inoculum and the infections in all host individuals would be required to distinguish between these two hypotheses.