Genomic and transcriptomic evidence for descent from Plasmodium and loss of blood schizogony in Hepatocystis parasites from naturally infected red colobus monkeys

Abstract

Hepatocystis is a genus of single-celled parasites infecting monkeys, bats and squirrels. Although thought to descend from malaria parasites (Plasmodium spp.), Hepatocystis spp. are thought not to undergo replication in the bloodthe part of the Plasmodium life cycle which causes the symptoms of malaria. Furthermore, Hepatocystis is transmitted by midges, not mosquitoes. Comparative genomics of Hepatocystis and Plasmodium species therefore presents an opportunity to better understand some of the most important aspects of malaria parasite biology. We were able to generate a draft genome for Hepatocystis using DNA sequencing reads from the blood of a naturally infected red colobus monkey. We provide robust phylogenetic support for Hepatocystis as a sister group to Plasmodium parasites infecting rodents. We show transcriptomic support for a lack of replication in the blood and genomic support for a complete loss of a family of genes involved in red blood cell invasion. Our analyses highlight the rapid evolution of genes involved in parasite vector stages, revealing genes that may be critical for interactions between malaria parasites and mosquitoes.* including pseudogenes, duplications and partial genes, excluding non-coding RNA genes ** two small contigs have telomeric repeats (scaffold 2410 (5 telomeric repeats, scaffold 2364, 9 telomeric repeats))

Immunogenetic response to a malaria-like parasite in a wild primate

“…S3). This is consistent with expectations for chronic Hepatocystis infection, in which parasite life stages persist throughout the infection, potentially due to constant generation of new parasites rather than re-infection (Aunin et al, 2020).…”

“…The Ugandan red colobus monkey whole blood transcriptomic dataset was collected by Simons and colleagues (2019) as part of the effort to generate the red colobus monkey reference genome. The sampled individuals (N = 29) are from a habituated population in Kibale National Park, Uganda, where red colobus have been the subjects of many disease-related studies as a part of the the Kibale EcoHealth Project (Chapman et al, 2005(Chapman et al, , 2013Goldberg et al, 2008;Lauck et al, 2011;Simons et al, 2019;Aunin et al, 2020). To identify colobus monkey genes with expression correlated to Hepatocystis parasite levels, we aligned blood transcriptome reads to a concatenated host-parasite pseudo-reference genome (containing genomes of red colobus and Hepatocystis sp.)…”

“…1; Table S1). For Hepatocystis reads, we used published read counts for these samples (Aunin et al, 2020) excluding genes with expression in the top and bottom quartile to minimize the impact of genes with outlier expression.…”

“…Colobus genes that were down-regulated in response to Hepatocystis were not significantly enriched for these erythrocyte-related functional annotations (p = 1 for all). Although genes involved in interactions with red blood cells have been lost in Hepatocystis (Aunin et al, 2020), Hepatocystis has been 9/26 reported to induce anemia in primates (Garnham, 1966;Chang et al, 2011), which may mediate the link between parasitemia and these monkey RBC-related genes.…”

“…At least one species is able to host-switch between primate species (Thurber et al, 2013), but no human infections have been reported. Though nested within the Plasmodium genus as a sister taxon to bat-and rodent-infecting Plasmodium in particular (Galen et al, 2018), Hepatocystis parasites differ in their apparently lack of asexual replication in red blood cells and their use of midges as vectors (Aunin et al, 2020;Garnham, 1966).…”