Evolution of Resistance to Avian Malaria Infection in an Endemic Hawaiian Honeycreeper

Malaria parasites in the genus Plasmodium are ubiquitous infectious agents. Most avian species effectively manage infection and experience limited population effects, with a notable exception in the Hawaiian Islands. Since Hawaiian honeycreepers evolved over ~7 million years without blood parasites, the introduction of Plasmodium relictum had devastating consequences-including widespread extinctions and extirpations. However, honeycreeper species have been differentially affected by malaria. Using whole genome sequences for 35 O'ahu 'amakihi (Chlorodrepanis flava), we conducted a genome-wide association study to identify single nucleotide polymorphisms (SNPs) correlated with avian malaria infection. Infection status was determined using real-time PCR on blood samples. We identified 582 SNPs associated with malaria infection. Annotations included long ncRNAs, genes associated with transcription regulation, apoptosis, T-cell and complement activation, autophagosome assembly and transport, and intracellular calcium flux. By identifying genes regulating intracellular calcium ions, a key signaling molecule in Plasmodium replication, our work shows that host limitations on parasite replication may not solely depend on the adaptive immune response. Host responses can also involve restricting intracellular components essential for completion of parasite life cycles. This adds to a growing wildlife disease literature indicating a broad range of mechanisms of disease resistance rather than common pathways.