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

Author summary Hepatocystisparasites are single-celled organisms, closely related to thePlasmodiumspecies which cause malaria. ButHepatocystisare distinct-unlikePlasmodiumthey are thought not to replicate in the blood and cause little or no disease in their mammalian hosts. They are transmitted from one host to the next, not by mosquitoes, but by biting midges. In this study we generated a genome sequence forHepatocystis-the first time this data has ever been produced and analysed for this species. We compared genome sequences ofHepatocystisandPlasmodium, confirming thatHepatocystisis descended fromPlasmodium. We strengthened support for the absence of replication in the blood and, in line with this finding, discovered that genes involved in interaction with red blood cells have been lost inHepatocystis. Our analyses revealed rapid evolution of genes which are active when the parasite is in the insect vector, highlighting those which might be important for understanding interaction between malaria parasites and mosquitoes.Hepatocystishas a fascinating evolutionary story and is a powerful comparator for understanding malaria parasite biology. Hepatocystisis a genus of single-celled parasites infecting, amongst other hosts, monkeys, bats and squirrels. Although thought to have descended from malaria parasites (Plasmodiumspp.),Hepatocystisspp. are thought not to undergo replication in the blood-the part of thePlasmodiumlife cycle which causes the symptoms of malaria. Furthermore,Hepatocystisis transmitted by biting midges, not mosquitoes. Comparative genomics ofHepatocystisandPlasmodiumspecies 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 forHepatocystissp. using DNA sequencing reads from the blood of a naturally infected red colobus monkey. We provide robust phylogenetic support forHepatocystissp. as a sister group toPlasmodiumparasites 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.