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.

Summary

This work began when I did a BLAST search for a malaria parasite gene, and saw a closely matching gene that claimed to be from a monkey. When I investigated further I found that this “monkey genome” contained substantial contamination from a genus of parasite called Hepatocystis that had been lurking in the monkey’s blood. The identification of the first substantial genomic data from this genus, which I initially described in a blog post, triggered a collaborative project between the originators of the data, former colleagues at the Sanger Institute, and myself to characterise this genome revealing the genomic basis of this parasite’s unique biology.

Publication
PLoS Pathogens
Theo Sanderson
Theo Sanderson
Sir Henry Wellcome Fellow

Biologist developing tools to scale malaria reverse genetics.