Single-cell genome sequencing of protozoan parasites

• Published in: Trends in parasitology 2021-09, Vol.37 (9), p.803-814
• Main Authors: Dia, Aliou, Cheeseman, Ian H.
• Format: Article
• Language: English
• Subjects: Eukaryota - genetics; genetic diversity; Genetic Variation; Genome, Protozoan - genetics; Parasitology - methods; Single-Cell Analysis - methods; single-cell isolation; single-cell multi-omics; single-cell sequencing; whole-genome amplification
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2021.05.013

Despite considerable genetic variation within hosts, most parasite genome sequencing studies focus on bulk samples composed of millions of cells. Analysis of bulk samples is biased toward the dominant genotype, concealing cell-to-cell variation and rare variants. To tackle this, single-cell sequencing approaches have been developed and tailored to specific host–parasite systems. These are allowing the genetic diversity and kinship in complex parasite populations to be deciphered and for de novo genetic variation to be captured. Here, we outline the methodologies being used for single-cell sequencing of parasitic protozoans, such as Plasmodium and Leishmania spp., and how these tools are being applied to understand parasite biology. In many host–parasite systems an infected host may carry several different pathogen genotypes. Genetic variation is associated with the mechanism of evolutionary adaption.Single-cell genomics has emerged as a powerful method for deciphering the genetic diversity and complexity of pathogens within an infection and allowing the estimation of relatedness between haplotypes. Consequently, this has led to a better understanding of pathogen transmission and adaptation.With a single-cell approach, in addition to estimating the pre-existing genetic variants within an infection, it is also possible to track de novo mutations; this allows us to evaluate the relative contribution of each type of variation.Finally, combination of single-cell genomics with single-cell transcriptomics from the same cell will bring new light on understanding phenotypic adaptation traits driven by genetic variation.