Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria

Abstract

BackgroundMicroarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a ‘just-in-time’ cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. However, direct analysis of transcription in P. falciparum blood-stage parasites obtained from the blood of infected patients suggests that parasite gene expression may be modulated by factors present in the in vivo environment of the host. The aim of this study was to examine changes in gene expression of the rodent malaria parasite, Plasmodium yoelii 17X, while varying the in vivo setting of replication.MethodsUsing P. yoelii 17X parasites replicating in vivo, differential gene expression in parasites isolated from individual mice, from independent infections, during ascending, peak and descending parasitaemia and in the presence and absence of host antibody responses was examined using P. yoelii DNA microarrays. A genome-wide analysis to identify coordinated changes in groups of genes associated with specific biological pathways was a primary focus, although an analysis of the expression patterns of two multi-gene families in P. yoelii, the yir and pyst-a families, was also completed.ResultsAcross experimental conditions, transcription was surprisingly stable with little evidence for distinct transcriptional states or for consistent changes in specific pathways. Differential gene expression was greatest when comparing differences due to parasite load and/or host cell availability. However, the number of differentially expressed genes was generally low. Of genes that were differentially expressed, many involved biologically diverse pathways. There was little to no differential expression of members of the yir and pyst-a multigene families that encode polymorphic proteins associated with the membrane of infected erythrocytes. However, a relatively large number of these genes were expressed during blood-stage infection regardless of experimental condition.ConclusionsTaken together, these results indicate that 1) P. yoelii gene expression remains stable in the presence of a changing host environment, and 2) concurrent expression of a large number of the polymorphic yir and pyst-a genes, rather than differential expression in response to specific host factors, may in itself limit the effectiveness of host immune responses.

Comparative single-cell transcriptional atlases of Babesia species reveal conserved and species-specific expression profiles

“…Interestingly, there are visible points of transition in the peak expression time that seem to match well with cell division cycle phases, indicating that shifts in peak expression govern the progression of the cell division cycle. This “just-in-time” expression pattern profile is also seen in other parasite species [ 23 , 24 , 64 – 66 ], supporting the notion that replication cycle genes are organized into clusters of co-expressed/co-regulated genes that may be functionally related. A heatmap of 377 conserved replication cycle DEGs across all species ( Fig 4C ) ordered by their progression in B .…”

Variant surface antigens of malaria parasites: functional and evolutionary insights from comparative gene family classification and analysis

“…More recently, RBC membrane localization of a pyst-a homolog (PBANKA_083680) has also been demonstrated in P. berghei [51]. Pyst-a genes are concurrently expressed in large numbers without evidence of differential expression in response to different host environments [52], suggesting that altering expression of pyst-a gene family members is not an immune evasion strategy of the parasite. Using bioinformatics sequence and structural analysis we predict the existence of a StAR-related lipid-transfer (START) domain in pyst-a proteins (Figure 2).…”

Comparative single-cell transcriptional atlases ofBabesiaspecies reveal conserved and species-specific expression profiles

“…The heatmaps show that clusters of marker genes peak at similar times with peak-time expression gradually shifting through the replication cycle. This "just-in-time expression" pattern profile is also seen in other parasite species(23,24,(66)(67)(68), indicating that replication cycle genes are organized into clusters of coexpressed/co-regulated genes that may be functionally related. Heatmap of 377 conserved replication cycle markers across all species (Fig 4A) ordered by their progression in B. divergens adapted to either human or bovine RBCs show a more similar progression pattern compared to B. bovis or B. bigemina (Fig SI 4), as also seen with the UMAP projection (Fig 1).…”