Genomic scale analysis of lateral gene transfer in Apicomplexan parasites: insights into early eukaryotic evolution, host-pathogen interaction and drug target development

SUMMARY Early electron microscopy studies revealed the elaborate cellular features that define the unique adaptations of apicomplexan parasites. Among these were bulbous rhoptry (ROP) organelles and small, dense granules (GRAs), both of which are secreted during invasion of host cells. These early morphological studies were followed by the exploration of the cellular contents of these secretory organelles, revealing them to be comprised of highly divergent protein families with few conserved domains or predicted functions. In parallel, studies on host-pathogen interactions identified many host signaling pathways that were mysteriously altered by infection. It was only with the advent of forward and reverse genetic strategies that the connections between individual parasite effectors and the specific host pathways that they targeted finally became clear. The current repertoire of parasite effectors includes ROP kinases and pseudokinases that are secreted during invasion and that block host immune pathways. Similarly, many secretory GRA proteins alter host gene expression by activating host transcription factors, through modification of chromatin, or by inducing small noncoding RNAs. These effectors highlight novel mechanisms by which T. gondii has learned to harness host signaling to favor intracellular survival and will guide future studies designed to uncover the additional complexity of this intricate host-pathogen interaction.

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Horizontal Gene Transfers from Bacteria toEntamoebaComplex: A Strategy for Dating Events along Species Divergence

Journal of Parasitology Research ◽

10.1155/2016/3241027 ◽

2016 ◽

Vol 2016 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Miguel Romero ◽

R. Cerritos ◽

Cecilia Ximenez

Keyword(s):

Gene Transfer ◽

Horizontal Gene Transfer ◽

Entamoeba Histolytica ◽

Lateral Gene Transfer ◽

Adaptive Radiation ◽

Fossil Record ◽

Evolutionary History ◽

Divergence Time ◽

Eukaryotic Evolution ◽

History Of

Horizontal gene transfer has proved to be relevant in eukaryotic evolution, as it has been found more often than expected and related to adaptation to certain niches. A relatively large list of laterally transferred genes has been proposed and evaluated for the parasiteEntamoeba histolytica. The goals of this work were to elucidate the importance of lateral gene transfer along the evolutionary history of some members of the genusEntamoeba, through identifying donor groups and estimating the divergence time of some of these events. In order to estimate the divergence time of some of the horizontal gene transfer events, the dating of someEntamoebaspecies was necessary, following an indirect dating strategy based on the fossil record of plausible hosts. The divergence betweenE. histolyticaandE. nuttalliiprobably occurred 5.93 million years ago (Mya); this lineage diverged fromE. dispar9.97 Mya, while the ancestor of the latter separated fromE. invadens68.18 Mya. We estimated times for 22 transferences; the most recent occurred 31.45 Mya and the oldest 253.59 Mya. Indeed, the acquisition of genes through lateral transfer may have triggered a period of adaptive radiation, thus playing a major role in the evolution of theEntamoebagenus.

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Divergent features of the coenzyme Q:cytochrome c oxidoreductase complex in Toxoplasma gondii parasites

PLoS Pathogens ◽

10.1371/journal.ppat.1009211 ◽

2021 ◽

Vol 17 (2) ◽

pp. e1009211

Author(s):

Jenni A. Hayward ◽

Esther Rajendran ◽

Soraya M. Zwahlen ◽

Pierre Faou ◽

Giel G. van Dooren

Keyword(s):

Toxoplasma Gondii ◽

Drug Target ◽

Protein Composition ◽

Complex Iii ◽

Mitochondrial Electron Transport Chain ◽

Eukaryotic Evolution ◽

Mitochondrial Oxygen Consumption ◽

Apicomplexan Parasites ◽

Transport Chain ◽

Important Drug

The mitochondrion is critical for the survival of apicomplexan parasites. Several major anti-parasitic drugs, such as atovaquone and endochin-like quinolones, act through inhibition of the mitochondrial electron transport chain at the coenzyme Q:cytochrome c oxidoreductase complex (Complex III). Despite being an important drug target, the protein composition of Complex III of apicomplexan parasites has not been elucidated. Here, we undertake a mass spectrometry-based proteomic analysis of Complex III in the apicomplexan Toxoplasma gondii. Along with canonical subunits that are conserved across eukaryotic evolution, we identify several novel or highly divergent Complex III components that are conserved within the apicomplexan lineage. We demonstrate that one such subunit, which we term TgQCR11, is critical for parasite proliferation, mitochondrial oxygen consumption and Complex III activity, and establish that loss of this protein leads to defects in Complex III integrity. We conclude that the protein composition of Complex III in apicomplexans differs from that of the mammalian hosts that these parasites infect.

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Genome expansion in early eukaryotes drove the transition from lateral gene transfer to meiotic sex

eLife ◽

10.7554/elife.58873 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 1

Author(s):

Marco Colnaghi ◽

Nick Lane ◽

Andrew Pomiankowski

Keyword(s):

Gene Transfer ◽

Genome Size ◽

Lateral Gene Transfer ◽

Selective Pressure ◽

Environmental Dna ◽

Theoretical Models ◽

Deleterious Mutations ◽

Eukaryotic Evolution ◽

Haploid Population ◽

Recombination Length

Prokaryotes acquire genes from the environment via lateral gene transfer (LGT). Recombination of environmental DNA can prevent the accumulation of deleterious mutations, but LGT was abandoned by the first eukaryotes in favour of sexual reproduction. Here we develop a theoretical model of a haploid population undergoing LGT which includes two new parameters, genome size and recombination length, neglected by previous theoretical models. The greater complexity of eukaryotes is linked with larger genomes and we demonstrate that the benefit of LGT declines rapidly with genome size. The degeneration of larger genomes can only be resisted by increases in recombination length, to the same order as genome size – as occurs in meiosis. Our results can explain the strong selective pressure towards the evolution of sexual cell fusion and reciprocal recombination during early eukaryotic evolution – the origin of meiotic sex.

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The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites

10.1101/870949 ◽

2019 ◽

Cited By ~ 1

Author(s):

Feifei Xu ◽

Alejandro Jiménez-González ◽

Elin Einarsson ◽

Ásgeir Ástvaldsson ◽

Dimitra Peirasmaki ◽

...

Keyword(s):

Gene Transfer ◽

Virulence Factors ◽

Lateral Gene Transfer ◽

Cysteine Proteases ◽

Surface Antigens ◽

Giardia Intestinalis ◽

Host Pathogen Interactions ◽

Host Pathogen ◽

Giardia Muris

AbstractDiplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the G. muris – mouse pathosystem.Author summaryThe Giardia genus comprises eukaryotic single-celled parasites that infect many animals. The Giardia intestinalis species complex, which can colonize and cause diarrheal disease in humans and different animal hosts has been extensively explored at the genomic and cell biologic levels. Other Giardia species, such as the mouse parasite Giardia muris, have remained uncharacterized at the genomic level, hampering our understanding of in vivo host-pathogen interactions and the impact of host dependence on the evolution of the Giardia genus. We discovered that the G. muris genome encodes many of the same virulence factors as G. intestinalis. The G. muris genome has undergone genome contraction, potentially in response to a more defined infective niche in the murine host. We describe differences in metabolic and microbiome modulatory gene repertoire, mediated mainly by lateral gene transfer, that could be important for understanding infective success across the Giardia genus. Our findings provide new insights for the use of G. muris as a powerful model for exploring host-pathogen interactions in giardiasis.

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