+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites



Comparative genome-wide analysis and evolutionary history of haemoglobin-processing and haem detoxification enzymes in malarial parasites



Malaria Journal 15: 51



Malaria parasites have evolved a series of intricate mechanisms to survive and propagate within host red blood cells. Intra-erythrocytic parasitism requires these organisms to digest haemoglobin and detoxify iron-bound haem. These tasks are executed by haemoglobin-specific proteases and haem biocrystallization factors that are components of a large multi-subunit complex. Since haemoglobin processing machineries are functionally and genetically linked to the modes of action and resistance mechanisms of several anti-malarial drugs, an understanding of their evolutionary history is important for drug development and drug resistance prevention. Maximum likelihood trees of genetic repertoires encoding haemoglobin processing machineries within Plasmodium species, and with the representatives of Apicomplexan species with various host tropisms, were created. Genetic variants were mapped onto existing three-dimensional structures. Genome-wide single nucleotide polymorphism data were used to analyse the selective pressure and the effect of these mutations at the structural level. Recent expansions in the falcipain and plasmepsin repertoires are unique to human malaria parasites especially in the Plasmodium falciparum and P. reichenowi lineage. Expansion of haemoglobin-specific plasmepsins occurred after the separation event of Plasmodium species, but the other members of the plasmepsin family were evolutionarily conserved with one copy for each sub-group in every Apicomplexan species. Haemoglobin-specific falcipains are separated from invasion-related falcipain, and their expansions within one specific locus arose independently in both P. falciparum and P. vivax lineages. Gene conversion between P. falciparum falcipain 2A and 2B was observed in artemisinin-resistant strains. Comparison between the numbers of non-synonymous and synonymous mutations suggests a strong selective pressure at falcipain and plasmepsin genes. The locations of amino acid changes from non-synonymous mutations mapped onto protein structures revealed clusters of amino acid residues in close proximity or near the active sites of proteases. A high degree of polymorphism at the haemoglobin processing genes implicates an imposition of selective pressure. The identification in recent years of functional redundancy of haemoglobin-specific proteases makes them less appealing as potential drug targets, but their expansions, especially in the human malaria parasite lineages, unequivocally point toward their functional significance during the independent and repetitive adaptation events in malaria parasite evolutionary history.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 057458043

Download citation: RISBibTeXText

PMID: 26821618

DOI: 10.1186/s12936-016-1097-9


Related references

Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites. Proceedings of the National Academy of Sciences of the United States of America 115(36): E8450-E8459, 2018

Comparative genome analysis of six malarial parasites using codon usage bias based tools. Bioinformation 8(24): 1230-1239, 2013

Genome-wide survey and evolutionary analysis of trypsin proteases in apicomplexan parasites. Genomics, Proteomics and Bioinformatics 8(2): 103-112, 2010

A genome-wide analysis of coatomer protein (COP) subunits of apicomplexan parasites and their evolutionary relationships. Bmc Genomics 20(1): 98, 2019

The GH3 family in plants: genome wide analysis in rice and evolutionary history based on EST analysis. Gene 371(2): 279-290, 2006

Genome-Wide Evolutionary Analysis of Natural History and Adaptation in the World's Tigers. Current Biology 28(23): 3840-3849.E6, 2018

Mechanism of malarial haem detoxification inhibition by chloroquine. Biochemical Journal 355(Pt 2): 333-338, 2001

Genome-wide identification and comparative evolutionary analysis of the Dof transcription factor family in physic nut and castor bean. Peerj 7: E6354, 2019

Genome-wide comparative and evolutionary analysis of Calmodulin-binding Transcription Activator (CAMTA) family in Gossypium species. Scientific Reports 8: 5573, 2018

Identification of a Salmonella ancillary copper detoxification mechanism by a comparative analysis of the genome-wide transcriptional response to copper and zinc excess. Microbiology 160(Pt 8): 1659-1669, 2015

A genome-wide analysis of array-based comparative genomic hybridization (CGH) data to detect intra-species variations and evolutionary relationships. Plos One 4(11): E7978, 2010

A genome-wide comparative evolutionary analysis of herpes simplex virus type 1 and varicella zoster virus. Plos One 6(7): E22527, 2011

Genome-wide analysis of UDP-glycosyltransferase super family in Brassica rapa and Brassica oleracea reveals its evolutionary history and functional characterization. Bmc Genomics 18(1): 474, 2018

Genome-wide analysis of myxobacterial two-component systems: genome relatedness and evolutionary changes. Bmc Genomics 16: 780, 2016

Large differences in the genome organization of different plant Trypanosomatid parasites (Phytomonas spp.) reveal wide evolutionary divergences between taxa. Infection, Genetics and Evolution 9(2): 235-240, 2009