Comparative analysis of low complexity regions in Plasmodia

Chaudhry, Sophia; Lwin, N.; Phelan, Doug; Escalante, Ananías A.; Battistuzzi, Fabia U.

doi:10.1038/s41598-017-18695-y

Cited by 26 publications

(23 citation statements)

References 63 publications

(72 reference statements)

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“…2008). Recent studies have found that regions of low complexity tend to remain unchanged over evolutionary time and that composition preferences in the region are unrelated to compositional biases observed in the rest of the genome (Chaudhry et al. 2018).…”

Section: Discussionmentioning

confidence: 99%

Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.

Castillo

Nelson

Lyons

2019

Genome Biology and Evolution

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Plasmodium parasites are valuable models to understand how nucleotide composition affects mutation, diversification, and adaptation. No other observed eukaryotes have undergone such large changes in genomic Guanine–Cytosine (GC) content as seen in the genus Plasmodium (∼30% within 35–40 Myr). Although mutational biases are known to influence GC content in the human-infective Plasmodium vivax and Plasmodium falciparum ; no study has addressed how different gene functional classes contribute to genus-wide compositional changes, or if Plasmodium GC content variation is driven by natural selection. Here, we tested the hypothesis that certain gene processes and functions drive variation in global GC content between Plasmodium species. We performed a large-scale comparative genomic analysis using the genomes and predicted genes of 17 Plasmodium species encompassing a wide genomic GC content range. Genic GC content was sorted and divided into ten equally sized quantiles that were then assessed for functional enrichment classes. In agreement that selection on gene classes may drive genomic GC content, trans-membrane proteins were enriched within extreme GC content quantiles (Q1 and Q10). Specifically, variant surface antigens, which primarily interact with vertebrate immune systems, showed skewed GC content distributions compared with other trans-membrane proteins. Although a definitive causation linking GC content, expression, and positive selection within variant surface antigens from Plasmodium vivax , Plasmodium berghei , and Plasmodium falciparum could not be established, we found that regardless of genomic nucleotide composition, genic GC content and expression were positively correlated during trophozoite stages. Overall, these data suggest that, alongside mutational biases, functional protein classes drive Plasmodium GC content change.

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Section: Discussionmentioning

confidence: 99%

Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.

Castillo

Nelson

Lyons

2019

Genome Biology and Evolution

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“…berghei ) revealed conserved locations for these insertions, while their sizes and sequences vary significantly (S1 Fig). The insertion located in the anticodon-binding domain is characterized by single amino acid repeats [33]. Indeed, this insertion is composed of 30% asparagine residues.…”

Section: Resultsmentioning

confidence: 99%

“…Plasmodium aaRSs are longer than their homologs because they contain many peculiar, sequence-repetitive insertions [3]. Neither the synthesis nor the functions of these insertions are understood [33]; the presence of long single amino acid repeats often reduces the solubility of the recombinant protein, but they cannot be removed under penalty of obtaining an inactive protein ( e . g , [47]).…”

Section: Discussionmentioning

confidence: 99%

Plasmodium apicoplast tyrosyl-tRNA synthetase recognizes an unusual, simplified identity set in cognate tRNATyr

et al. 2018

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The life cycle of Plasmodium falciparum, the agent responsible for malaria, depends on both cytosolic and apicoplast translation fidelity. Apicoplast aminoacyl-tRNA synthetases (aaRS) are bacterial-like enzymes devoted to organellar tRNA aminoacylation. They are all encoded by the nuclear genome and are translocated into the apicoplast only after cytosolic biosynthesis. Apicoplast aaRSs contain numerous idiosyncratic sequence insertions: An understanding of the roles of these insertions has remained elusive and they hinder efforts to heterologously overexpress these proteins. Moreover, the A/T rich content of the Plasmodium genome leads to A/U rich apicoplast tRNA substrates that display structural plasticity. Here, we focus on the P. falciparum apicoplast tyrosyl-tRNA synthetase (Pf-apiTyrRS) and its cognate tRNATyr substrate (Pf-apitRNATyr). Cloning and expression strategies used to obtain an active and functional recombinant Pf-apiTyrRS are reported. Functional analyses established that only three weak identity elements in the apitRNATyr promote specific recognition by the cognate Pf-apiTyrRS and that positive identity elements usually found in the tRNATyr acceptor stem are excluded from this set. This finding brings to light an unusual behavior for a tRNATyr aminoacylation system and suggests that Pf-apiTyrRS uses primarily negative recognition elements to direct tyrosylation specificity.

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“…There is just one small change with enrichments of glutamate homopeptides in protein domains becoming significant (Table S4). Comparisons were also made with proteomes of P. yoelii, a malaria parasite of rodents, and P. vivax, a member of the CVK group of primate-infecting plasmodia (Chaudhry et al, 2018). P. yoelii has an overall approximately even predominance of N and K homopeptides, and P. vivax has predominance of K homopeptides rather than of N homopeptides (Table S4).…”

Section: Comparison Of Trends In Other Plasmodiamentioning

confidence: 99%

“…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 ). As well as being sites of polymorphic variation themselves ( Chaudhry et al, 2018 ), Pf LCRs are linked to increased single-nucleotide polymorphism in their vicinity ( Haerty & Golding, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

The relationship between protein domains and homopeptides in the Plasmodium falciparum proteome

Wang

Yang

Harrison

2020

PeerJ

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The proteome of the malaria parasite Plasmodium falciparum is notable for the pervasive occurrence of homopeptides or low-complexity regions (i.e., regions that are made from a small subset of amino-acid residue types). The most prevalent of these are made from residues encoded by adenine/thymidine (AT)-rich codons, in particular asparagine. We examined homopeptide occurrences within protein domains in P. falciparum. Homopeptide enrichments occur for hydrophobic (e.g., valine), or small residues (alanine or glycine) in short spans (<5 residues), but these enrichments disappear for longer lengths. We observe that short asparagine homopeptides (<10 residues long) have a dramatic relative depletion inside protein domains, indicating some selective constraint to keep them from forming. We surmise that this is possibly linked to co-translational protein folding, although there are specific protein domains that are enriched in longer asparagine homopeptides (≥10 residues) indicating a functional linkage for specific poly-asparagine tracts. Top gene ontology functional category enrichments for homopeptides associated with diverse protein domains include “vesicle-mediated transport”, and “DNA-directed 5′-3′ RNA polymerase activity”, with various categories linked to “binding” evidencing significant homopeptide depletions. Also, in general homopeptides are substantially enriched in the parts of protein domains that are near/in IDRs. The implications of these findings are discussed.

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Comparative analysis of low complexity regions in Plasmodia

Cited by 26 publications

References 63 publications

Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.

Tail Wags the Dog? Functional Gene Classes Driving Genome-Wide GC Content in Plasmodium spp.

Plasmodium apicoplast tyrosyl-tRNA synthetase recognizes an unusual, simplified identity set in cognate tRNATyr

The relationship between protein domains and homopeptides in the Plasmodium falciparum proteome

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