Homopolymer tract organization in the human malarial parasite Plasmodium falciparum and related Apicomplexan parasites

Abstract

BackgroundHomopolymeric tracts, particularly poly dA.dT, are enriched within the intergenic sequences of eukaryotic genomes where they appear to act as intrinsic regulators of nucleosome positioning. A previous study of the incomplete genome of the human malarial parasite Plasmodium falciparum reports a higher than expected enrichment of poly dA.dT tracts, far above that anticipated even in this highly AT rich genome. Here we report an analysis of the relative frequency, length and spatial arrangement of homopolymer tracts for the complete P. falciparum genome, extending this analysis to twelve additional genomes of Apicomplexan parasites important to human and animal health. In addition, using nucleosome-positioning data available for P. falciparum, we explore the correlation of poly dA.dT tracts with nucleosome-positioning data over key expression landmarks within intergenic regions.ResultsWe describe three apparent lineage-specific patterns of homopolymeric tract organization within the intergenic regions of these Apicomplexan parasites. Moreover, a striking pattern of enrichment of overly long poly dA.dT tracts in the intergenic regions of Plasmodium spp. uniquely extends into protein coding sequences. There is a conserved spatial arrangement of poly dA.dT immediately flanking open reading frames and over predicted core promoter sites. These key landmarks are all relatively depleted in nucleosomes in P. falciparum, as would be expected for poly dA.dT acting as nucleosome exclusion sequences.ConclusionsPrevious comparative studies of homopolymer tract organization emphasize evolutionary diversity; this is the first report of such an analysis within a single phylum. Our data provide insights into the evolution of homopolymeric tracts and the selective pressures at play in their maintenance and expansion.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-15-848) contains supplementary material, which is available to authorized users.

The nucleosome landscape ofPlasmodium falciparumreveals chromatin architecture and dynamics of regulatory sequences

“…Indeed we do observe local GC-content changes often accompanying the well-positioned nucleosomes at landmarks sites (Figure 3A , lower panel), which could potentially cause the observed positioning. Furthermore, combinations of polyA and/or polyT tracks were previously reported to influence local chromatin organization next to the ATG, STOP and TSS in both Dictyostelium and Plasmodium genomes ( 21 , 43 ). In addition, we observe enrichment of polyA/T tracks next to the splice junction and at the TTSs (Figure 3B ) showing that they are commonly associated with all landmark features and hence likely contribute to nucleosome positioning at these sites.…”

“…Long polymeric AAAAAA- or TTTTTT-stretches have also been claimed to possess nucleosome-repelling properties due to their intrinsic stiffness ( 2 ). A specific combination of polyA and polyT tracks has indeed been found to be a common feature of transcriptional or translational start and translational end sites in P. falciparum ( 43 ) and in D. discoideum ( 21 ). In our data, we also find clear enrichment of these sequences next to transcription start, splice and transcriptional termination sites.…”

23 Genome-wide and positional homopolymeric tract enrichment at promoter-exon boundaries and exclusion of nucleosomes inPlasmodiumspp. and related parasites

“…Previous studies of the incomplete genome of the human malarial parasite Plasmodium falciparum, reported a high enrichment of long poly dA.dT tracts, far above that expected for this AT rich genome (Dechering et al, 1998;Zhou et al, 2004). We report an analysis of the relative frequency, length and spatial arrangement of homopolymer tracts for the complete P. falciparum genome, extending this analysis to 12 additional Apicomplexan parasite genomes (Russell et al, 2014). Using nucleosome positioning data available for P. falciparum, we explore the correlation of poly dA.dT tracts with nucleosome positioning over key expression landmarks within intergenic regions.…”

Peer Review #3 of "The relationship between protein domains and homopeptides in the Plasmodium falciparum proteome (v0.2)"

“…LCRs can be classified into three distinct types, including a high G+C type that is linked to recombination hotspots (Zilversmit et al 2010). There is a pattern of enrichment of long intergenic poly(AT) tracts in Plasmodium species, some of which are immediately adjacent to genes and run into them (Russell et al 2014). Although asparagine is preferred in LCRs of Pf, a different residue type with AT-rich codons (lysine) is more prominent in the CVK group, which is a set of four primate-infecting plasmodia (Chaudhry et al 2018).…”