PvGAMA reticulocyte binding activity: predicting conserved functional regions by natural selection analysis

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Abstract

Background

Adhesin proteins are used by Plasmodium parasites to bind and invade target cells. Hence, characterising molecules that participate in reticulocyte interaction is key to understanding the molecular basis of Plasmodium vivax invasion. This study focused on predicting functionally restricted regions of the P. vivax GPI-anchored micronemal antigen ( PvGAMA) and characterising their reticulocyte binding activity.

Results

The pvgama gene was initially found in P. vivax VCG-I strain schizonts. According to the genetic diversity analysis, PvGAMA displayed a size polymorphism very common for antigenic P. vivax proteins. Two regions along the antigen sequence were highly conserved among species, having a negative natural selection signal. Interestingly, these regions revealed a functional role regarding preferential target cell adhesion.

Conclusions

To our knowledge, this study describes PvGAMA reticulocyte binding properties for the first time. Conserved functional regions were predicted according to natural selection analysis and their binding ability was confirmed. These findings support the notion that PvGAMA may have an important role in P. vivax merozoite adhesion to its target cells.

Electronic supplementary material

The online version of this article (doi:10.1186/s13071-017-2183-8) contains supplementary material, which is available to authorized users.

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Most cited references 50

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Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology.

Wayne Delport, Art Poon, Simon D W Frost … (2010)

Datamonkey is a popular web-based suite of phylogenetic analysis tools for use in evolutionary biology. Since the original release in 2005, we have expanded the analysis options to include recently developed algorithmic methods for recombination detection, evolutionary fingerprinting of genes, codon model selection, co-evolution between sites, identification of sites, which rapidly escape host-immune pressure and HIV-1 subtype assignment. The traditional selection tools have also been augmented to include recent developments in the field. Here, we summarize the analyses options currently available on Datamonkey, and provide guidelines for their use in evolutionary biology. Availability and documentation: http://www.datamonkey.org.

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A random effects branch-site model for detecting episodic diversifying selection.

Sergei L. Kosakovsky Pond, Ben Murrell, Mathieu Fourment … (2011)

Adaptive evolution frequently occurs in episodic bursts, localized to a few sites in a gene, and to a small number of lineages in a phylogenetic tree. A popular class of "branch-site" evolutionary models provides a statistical framework to search for evidence of such episodic selection. For computational tractability, current branch-site models unrealistically assume that all branches in the tree can be partitioned a priori into two rigid classes--"foreground" branches that are allowed to undergo diversifying selective bursts and "background" branches that are negatively selected or neutral. We demonstrate that this assumption leads to unacceptably high rates of false positives or false negatives when the evolutionary process along background branches strongly deviates from modeling assumptions. To address this problem, we extend Felsenstein's pruning algorithm to allow efficient likelihood computations for models in which variation over branches (and not just sites) is described in the random effects likelihood framework. This enables us to model the process at every branch-site combination as a mixture of three Markov substitution models--our model treats the selective class of every branch at a particular site as an unobserved state that is chosen independently of that at any other branch. When benchmarked on a previously published set of simulated sequences, our method consistently matched or outperformed existing branch-site tests in terms of power and error rates. Using three empirical data sets, previously analyzed for episodic selection, we discuss how modeling assumptions can influence inference in practical situations.

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Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry.

Paal S. Andersen, Andrew P. Waters, Neil Hall … (2002)

The annotated genomes of organisms define a 'blueprint' of their possible gene products. Post-genome analyses attempt to confirm and modify the annotation and impose a sense of the spatial, temporal and developmental usage of genetic information by the organism. Here we describe a large-scale, high-accuracy (average deviation less than 0.02 Da at 1,000 Da) mass spectrometric proteome analysis of selected stages of the human malaria parasite Plasmodium falciparum. The analysis revealed 1,289 proteins of which 714 proteins were identified in asexual blood stages, 931 in gametocytes and 645 in gametes. The last two groups provide insights into the biology of the sexual stages of the parasite, and include conserved, stage-specific, secreted and membrane-associated proteins. A subset of these proteins contain domains that indicate a role in cell-cell interactions, and therefore can be evaluated as potential components of a malaria vaccine formulation. We also report a set of peptides with significant matches in the parasite genome but not in the protein set predicted by computational methods.

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Author and article information

Contributors

Luis A. Baquero: labs1990@gmail.com

Darwin A. Moreno-Pérez: darandmorper@gmail.com

Diego Garzón-Ospina: degarzon@gmail.com

Johanna Forero-Rodríguez: lady2007_10@hotmail.com

Heidy D. Ortiz-Suárez: danilyn.17@gmail.com

Manuel A. Patarroyo: mapatarr.fidic@gmail.com

Journal

Journal ID (nlm-ta): Parasit Vectors

Journal ID (iso-abbrev): Parasit Vectors

Title: Parasites & Vectors

Publisher: BioMed Central (London )

ISSN (Electronic): 1756-3305

Publication date (Electronic): 19 May 2017

Publication date PMC-release: 19 May 2017

Publication date Collection: 2017

Volume: 10

Electronic Location Identifier: 251

Affiliations

[1 ]ISNI 0000 0004 0629 6527, GRID grid.418087.2, Molecular Biology and Immunology Department, , Fundación Instituto de Inmunología de Colombia (FIDIC), ; Carrera 50 No. 26-20, Bogotá DC, Colombia

[2 ]ISNI 0000 0001 2205 5940, GRID grid.412191.e, PhD Programme in Biomedical and Biological Sciences, , Universidad del Rosario, ; Carrera 24 No. 63C-69, Bogotá DC, Colombia

[3 ]ISNI 0000 0001 2205 5940, GRID grid.412191.e, Basic Sciences Department, , School of Medicine and Health Sciences, Universidad del Rosario, ; Carrera 24 No. 63C-69, Bogotá DC, Colombia

Article

Publisher ID: 2183

DOI: 10.1186/s13071-017-2183-8

PMC ID: 5438544

PubMed ID: 28526096

SO-VID: 834b3bba-a469-440c-9889-ffcc4068f759

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 27 October 2016

Date accepted : 10 May 2017

Funding

Funded by: FundRef http://dx.doi.org/http://dx.doi.org/10.13039/100007637, Departamento Administrativo de Ciencia, Tecnología e Innovación;

Award ID: RC#0309-2013

Funded by: FundRef http://dx.doi.org/10.13039/100007637, Departamento Administrativo de Ciencia, Tecnología e Innovación;

Award ID: 0719-2013

Award ID: 0555-2015

Award Recipient : Johanna Forero-Rodríguez Heidy D. Ortiz-Suárez

Custom metadata

ScienceOpen disciplines: Parasitology

Keywords: adhesin protein,plasmodium vivax,genetic diversity,conserved functional region,reticulocyte binding activity

Data availability:

ScienceOpen disciplines: Parasitology

Keywords: adhesin protein, plasmodium vivax, genetic diversity, conserved functional region, reticulocyte binding activity

PvGAMA reticulocyte binding activity: predicting conserved functional regions by natural selection analysis

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Abstract

Background

Results

Conclusions

Electronic supplementary material

Related collections

Malaria vaccine development

Most cited references 50

Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology.

A random effects branch-site model for detecting episodic diversifying selection.

Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry.

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