Comparative genomics of Plasmodium yoelii nigeriensis N67 and N67C: genome-wide polymorphisms, differential gene expression, and drug resistance.

Autor: Wu J; Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD, 20852, USA., Oguz C; Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Teklemichael AA; Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD, 20852, USA., Xu F; Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD, 20852, USA., Stadler RV; Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD, 20852, USA., Lucky AB; Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan., Liu S; State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian, 361102, China., Kaneko O; Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, 852-8523, Japan., Lack J; Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA., Su XZ; Malaria Functional Genomics Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD, 20852, USA. xsu@niaid.nih.gov.
Jazyk: angličtina
Zdroj: BMC genomics [BMC Genomics] 2024 Nov 05; Vol. 25 (1), pp. 1035. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1186/s12864-024-10961-4
Abstrakt: Background: The study of rodent malaria parasites has significantly advanced our understanding of malaria parasite biology and host responses to parasite infections. There are four well-characterized rodent malaria parasite species (Plasmodium yoelii, P. chabaudi, P. berghei, and P. vinckei). Each species also has multiple strains that cause different disease phenotypes. P. yoelii nigeriensis N67C and N67, two isogenic parasites, are particularly intriguing as they differ in virulence and incite different immune responses in mice. The genome of the N67 parasite has been assembled recently, but not that of N67C. This study used PacBio HiFi sequencing data to assemble the N67C genome, compared the two genomes, and performed RNA sequencing to identify polymorphisms and differentially expressed genes (DEGs).
Results: The assembled N67C parasite genome consisted of 16 scaffolds and three contigs of approximately 22.5 Mb with 100% and 96.6% completeness based on well-characterized single-copy orthologs specific to the Apicomplexa phylum and the Plasmodium genus, respectively. A comparison between the annotated N67C and N67 genomes revealed 133 single nucleotide polymorphisms (SNPs) and 75 indels. Among the polymorphic sites, an S (N67) to N (N67C) amino acid substitution at position 114 (S114N) in the dihydrofolate reductase-thymidylate synthase (DHFR-TS) confers resistance to pyrimethamine in mice. Additionally, 60 differentially expressed single-copy genes (DEGs) were detected after comparing mRNA levels between the two parasites. Starting with the predicted and annotated 5,681 N67C and 5,749 N67 genes, we identified 4,641 orthogroups that included at least one gene from the four P. yoelii parasites (N67, N67C, 17X, and YM), whereas 758 orthogroups showed subspecies or strain-specific patterns.
Conclusion: The identification of polymorphic sites between the N67 and N67C genomes, along with the detection of the DEGs, may provide crucial insights into the variations in parasite drug responses and disease severity between these two isogenic parasites. The functional characterization of these genetic differences and candidate genes will deepen our understanding of disease mechanisms and pave the way for developing more effective control measures against malaria.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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