Single-genome sequencing reveals within-host evolution of human malaria parasites

Cell Host Microbe. 2021 Oct 13;29(10):1496-1506.e3. doi: 10.1016/j.chom.2021.08.009. Epub 2021 Sep 6.

Abstract

Population genomics of bulk malaria infections is unable to examine intrahost evolution; therefore, most work has focused on the role of recombination in generating genetic variation. We used single-cell sequencing protocol for low-parasitaemia infections to generate 406 near-complete single Plasmodium vivax genomes from 11 patients sampled during sequential febrile episodes. Parasite genomes contain hundreds of de novo mutations, showing strong signatures of selection, which are enriched in the ApiAP2 family of transcription factors, known targets of adaptation. Comparing 315 P. falciparum single-cell genomes from 15 patients with our P. vivax data, we find broad complementary patterns of de novo mutation at the gene and pathway level, revealing the importance of within-host evolution during malaria infections.

Keywords: Parasite mutations; Plasmodium falciparum; Plasmodium vivax; de-novo mutations; genetic diversity; malaria; malaria low parasitaemia; parasite relatedness; single-cell sequencing; within-host evolution.

MeSH terms

  • Animals
  • Evolution, Molecular
  • Genetic Variation
  • Genome, Protozoan*
  • Humans
  • Malaria, Vivax / genetics
  • Malaria, Vivax / parasitology*
  • Mutation
  • Plasmodium vivax / cytology
  • Plasmodium vivax / genetics*
  • Plasmodium vivax / metabolism
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Single-Cell Analysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Protozoan Proteins
  • Transcription Factors