Long-Read Genome Assembly and Gene Model Annotations for the Rodent Malaria ParasitePlasmodium yoelii17XNL

Abstract

AbstractMalaria causes over 200 million infections and over 600 thousand fatalities each year, with most cases attributed to a human-infectiousPlasmodiumspecies,Plasmodium falciparum. Many rodent-infectiousPlasmodiumspecies, likePlasmodium berghei, Plasmodium chabaudi, andPlasmodium yoelii, have been used as genetically tractable model species that can expedite studies of this pathogen. In particular,P. yoeliiis an especially good model for investigating the mosquito and liver stages of parasite development because key attributes closely resemble those ofP. falciparum. Because of its importance to malaria research, in 2002 the 17XNL strain ofP. yoeliiwas the first rodent malaria parasite to be sequenced. While sequencing and assembling this genome was a breakthrough effort, the final assembly consisted of >5000 contiguous sequences that impacted the creation of annotated gene models. While other important rodent malaria parasite genomes have been sequenced and annotated since then, including the relatedP. yoelii17X strain, the 17XNL strain has not. As a result, genomic data for 17X has become thede factoreference genome for the 17XNL strain while leaving open questions surrounding possible differences between the 17XNL and 17X genomes. In this work, we present a high-quality genome assembly forP. yoelii17XNL using HiFi PacBio long-read DNA sequencing. In addition, we use Nanopore long-read direct RNA-seq and Illumina short-read sequencing of mixed blood stages to create complete gene models that include not only coding sequences but also alternate transcript isoforms, and 5’ and 3’ UTR designations. A comparison of the 17X and this new 17XNL assembly revealed biologically meaningful differences between the strains due to the presence of coding sequence variants. Taken together, our work provides a new genomic and gene expression framework for studies with this commonly used rodent malaria model species.