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, amongst other hosts, monkeys, bats and squirrels. Although thought to have descended from malaria parasites (Plasmodium spp.), Hepatocystis spp. are thought not to undergo replication in the blood–the part of the Plasmodium life cycle which causes the symptoms of malaria. Furthermore, Hepatocystis is transmitted by biting 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 sp. using DNA sequencing reads from the blood of a naturally infected red colobus monkey. We provide robust phylogenetic support for Hepatocystis sp. 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. Hepatocystis parasites are single-celled organisms, closely related to the Plasmodium species which cause malaria. But Hepatocystis are distinct–unlike Plasmodium they 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 for Hepatocystis–the first time this data has ever been produced and analysed for this species. We compared genome sequences of Hepatocystis and Plasmodium, confirming that Hepatocystis is descended from Plasmodium. 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 in Hepatocystis. 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. Hepatocystis has a fascinating evolutionary story and is a powerful comparator for understanding malaria parasite biology.