Explore the vast range of titles available.

Virtually all plants and animals, including humans, are home to symbiotic microorganisms. Symbiotic interactions can be neutral, harmful or have beneficial effects on the host organism. However, growing evidence suggests that microbial symbionts can evolve rapidly, resulting in drastic transitions along the parasite–mutualist continuum. In this Review, we integrate theoretical and empirical findings to discuss the mechanisms underpinning these evolutionary shifts, as well as the ecological drivers and why some host–microorganism interactions may be stuck at the end of the continuum. In addition to having biomedical consequences, understanding the dynamic life of microorganisms reveals how symbioses can shape an organism’s biology and the entire community, particularly in a changing world.Symbiotic interactions can be neutral, harmful or have beneficial effects for host organisms. In this Review, Drew, Stevens and King discuss the evolutionary transitions of host–microorganism symbioses along the parasite–mutualist continuum, the mechanisms underlying evolutionary changes, the selective pressures involved and common empirical approaches for studying them.

Supplementation with micronutrients, including vitamins, iron and zinc, is a key strategy to alleviate child malnutrition. However, association of gastrointestinal disorders with iron has led to ongoing debate over their administration. To better understand their impact on gut microbiota, we analyse the bacterial, protozoal, fungal and helminth communities of stool samples collected from a subset of 80 children at 12 and 24 months of age, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan (ClinicalTrials.gov identifier NCT00705445). We show that while bacterial diversity is reduced in supplemented children, vitamins and iron (as well as residence in a rural setting) may promote colonization with distinct protozoa and mucormycetes, whereas the addition of zinc appears to ameliorate this effect. We suggest that the risks and benefits of micronutrient interventions may depend on eukaryotic communities, potentially exacerbated by exposure to a rural setting. Larger studies are needed to evaluate the clinical significance of these findings and their impact on health outcomes. Micronutrient supplements are key to global efforts to address child malnutrition. Here, in a cohort of children, previously enrolled into a large cluster randomized controlled trial of micronutrient supplementation in Pakistan, Popovic et al . find that vitamins and iron increase carriage of protozoa and fungi in the gut, potentially disrupting the bacterial microbiome.

Studies in diverse biological systems have indicated that host–parasite co-evolution is responsible for the extraordinary genetic diversity seen in some genomic regions, such as major histocompatibility (MHC) genes in jawed vertebrates and resistance genes in plants. This diversity is believed to evolve under balancing selection on hosts by parasites. However, the mechanisms that link the genomic signatures in these regions to the underlying co-evolutionary process are only slowly emerging. We still lack a clear picture of the co-evolutionary concepts and of the genetic basis of the co-evolving phenotypic traits in the interacting antagonists. Emerging genomic tools that provide new options for identifying underlying genes will contribute to a fuller understanding of the co-evolutionary process.Host–parasite co-evolution is expected to leave signatures of selection in the genome of both antagonists. Ebert and Fields discuss what is known about these signatures, how they relate to co-evolutionary processes and how they can help identify the genes underlying the co-evolving phenotypes.

Controlled human malaria infections (CHMI) are a valuable tool to study parasite gene expression in vivo under defined conditions. In previous studies, virulence gene expression was analyzed in samples from volunteers infected with the Plasmodium falciparum (Pf) NF54 isolate, which is of African origin. Here, we provide an in-depth investigation of parasite virulence gene expression in malaria-naïve European volunteers undergoing CHMI with the genetically distinct Pf 7G8 clone, originating in Brazil. Differential expression of var genes, encoding major virulence factors of Pf, PfEMP1s, was assessed in ex vivo parasite samples as well as in parasites from the in vitro cell bank culture that was used to generate the sporozoites (SPZ) for CHMI (Sanaria PfSPZ Challenge (7G8)). We report broad activation of mainly B-type subtelomeric located var genes at the onset of a 7G8 blood stage infection in naïve volunteers, mirroring the NF54 expression study and suggesting that the expression of virulence-associated genes is generally reset during transmission from the mosquito to the human host. However, in 7G8 parasites, we additionally detected a continuously expressed single C-type variant, Pf7G8_040025600, that was most highly expressed in both pre-mosquito cell bank and volunteer samples, suggesting that 7G8, unlike NF54, maintains expression of some previously expressed var variants during transmission. This suggests that in a new host, the parasite may preferentially express the variants that previously allowed successful infection and transmission. Trial registration: ClinicalTrials.gov - NCT02704533 ; 2018-004523-36

Malaria infection involves an obligatory, yet clinically silent liver stage 1 , 2 . Hepatocytes operate in repeating units termed lobules, exhibiting heterogeneous gene expression patterns along the lobule axis 3 , but the effects of hepatocyte zonation on parasite development at the molecular level remain unknown. Here we combine single-cell RNA sequencing 4 and single-molecule transcript imaging 5 to characterize the host and parasite temporal expression programmes in a zonally controlled manner for the rodent malaria parasite Plasmodium berghei ANKA. We identify differences in parasite gene expression in distinct zones, including potentially co-adaptive programmes related to iron and fatty acid metabolism. We find that parasites develop more rapidly in the pericentral lobule zones and identify a subpopulation of periportally biased hepatocytes that harbour abortive infections, reduced levels of Plasmodium transcripts and parasitophorous vacuole breakdown. These ‘abortive hepatocytes’, which appear predominantly with high parasite inoculum, upregulate immune recruitment and key signalling programmes. Our study provides a resource for understanding the liver stage of Plasmodium infection at high spatial resolution and highlights the heterogeneous behaviour of both the parasite and the host hepatocyte. Single-cell RNA sequencing and single-molecule RNA transcript imaging have been used to characterize spatially and temporally resolved mouse liver and parasite expression programmes during infection with the rodent malaria parasite Plasmodium berghei ANKA.

Obligate intracellular Apicomplexa parasites share a unique invasion mechanism involving a tight interaction between the host cell and the parasite surfaces called the moving junction (MJ). The MJ, which is the anchoring structure for the invasion process, is formed by secretion of a macromolecular complex (RON2/4/5/8), derived from secretory organelles called rhoptries, into the host cell membrane. AMA1, a protein secreted from micronemes and associated with the parasite surface during invasion, has been shown in vitro to bind the MJ complex through a direct association with RON2. Here we show that RON2 is inserted as an integral membrane protein in the host cell and, using several interaction assays with native or recombinant proteins, we define the region that binds AMA1. Our studies were performed both in Toxoplasma gondii and Plasmodium falciparum and although AMA1 and RON2 proteins have diverged between Apicomplexa species, we show an intra-species conservation of their interaction. More importantly, invasion inhibition assays using recombinant proteins demonstrate that the RON2-AMA1 interaction is crucial for both T. gondii and P. falciparum entry into their host cells. This work provides the first evidence that AMA1 uses the rhoptry neck protein RON2 as a receptor to promote invasion by Apicomplexa parasites.

Lateral gene transfers (LGT), species to species transmission of genes by means other than direct inheritance from a common ancestor, have played significant role in shaping prokaryotic genomes and are involved in gain or transfer of important biological processes. Whether LGT significantly contributed to the composition of an animal genome is currently unclear. In nematodes, multiple LGT are suspected to have favored emergence of plant-parasitism. With the availability of whole genome sequences it is now possible to assess whether LGT have significantly contributed to the composition of an animal genome and to establish a comprehensive list of these events. We generated clusters of homologous genes and automated phylogenetic inference, to detect LGT in the genomes of root-knot nematodes and found that up to 3.34% of the genes originate from LGT of non-metazoan origin. After their acquisition, the majority of genes underwent series of duplications. Compared to the rest of the genes in these species, several predicted functional categories showed a skewed distribution in the set of genes acquired via LGT. Interestingly, functions related to metabolism, degradation or modification of carbohydrates or proteins were substantially more frequent. This suggests that genes involved in these processes, related to a parasitic lifestyle, have been more frequently fixed in these parasites after their acquisition. Genes from soil bacteria, including plant-pathogens were the most frequent closest relatives, suggesting donors were preferentially bacteria from the rhizosphere. Several of these bacterial genes are plasmid-borne, pointing to a possible role of these mobile genetic elements in the transfer mechanism. Our analysis provides the first comprehensive description of the ensemble of genes of non-metazoan origin in an animal genome. Besides being involved in important processes regarding plant-parasitism, genes acquired via LGT now constitute a substantial proportion of protein-coding genes in these nematode genomes.

Genes hitch a lift The horizontal transfer (HT) of genetic material between non-mating species, common in bacteria, is increasingly being recognized as a significant force in eukaryotic evolution. Most instances of HT described so far in metazoans involve mobile genetic elements — mainly transposons — but the mechanisms enabling this exchange between widely divergent species are unknown. Gilbert et al . now show that transposable elements spread between disparate species by hitch-hiking in the genomes of parasites shared by these species. Specifically, Rhodnius prolixus , an insect that feeds on the blood of tetrapods and which is the vector of Chagas disease in humans, carries four distinct transposon families in its genome that can invade the genomes of a range of tetrapods including the opossum and squirrel monkey. One of these transposon families is also present in the pond snail Lymnaea stagnalis , a vector of trematodes infecting many vertebrates. 'Horizontal gene transfer' refers to the passage of genetic material between non-mating species. Transposable elements (transposons) may be especially prone to horizontal gene transfer, but the mechanisms by which they can spread across diverged species have been elusive. Here it is shown that transposons can spread by hitchhiking in the genomes of parasites. The amount of DNA that can be transferred in this way underscores the impact of horizontal gene transfer on genome evolution. Horizontal transfer (HT), or the passage of genetic material between non-mating species, is increasingly recognized as an important force in the evolution of eukaryotic genomes 1 , 2 . Transposons, with their inherent ability to mobilize and amplify within genomes, may be especially prone to HT 3 , 4 , 5 , 6 , 7 . However, the means by which transposons can spread across widely diverged species remain elusive. Here we present evidence that host–parasite interactions have promoted the HT of four transposon families between invertebrates and vertebrates. We found that Rhodnius prolixus , a triatomine bug feeding on the blood of various tetrapods and vector of Chagas’ disease in humans, carries in its genome four distinct transposon families that also invaded the genomes of a diverse, but overlapping, set of tetrapods. The bug transposons are ∼98% identical and cluster phylogenetically with those of the opossum and squirrel monkey, two of its preferred mammalian hosts in South America. We also identified one of these transposon families in the pond snail Lymnaea stagnalis , a cosmopolitan vector of trematodes infecting diverse vertebrates, whose ancestral sequence is nearly identical and clusters with those found in Old World mammals. Together these data provide evidence for a previously hypothesized role of host–parasite interactions in facilitating HT among animals 3 , 7 . Furthermore, the large amount of DNA generated by the amplification of the horizontally transferred transposons supports the idea that the exchange of genetic material between hosts and parasites influences their genomic evolution.

Abstract Understanding the genomic basis of infectious disease is a fundamental objective in co-evolutionary theory with relevance to healthcare, agriculture, and epidemiology. Models of host-parasite co-evolution often assume that infection requires specific combinations of host and parasite genotypes. Co-evolving host and parasite loci are, therefore, expected to show associations that reflect an underlying infection/resistance allele matrix, yet little evidence for such genome-to-genome interactions has been observed among natural populations. We conducted a study to search for this genomic signature across 258 linked host (Daphnia magna) and parasite (Pasteuria ramosa) genomes. Our results show a clear signal of genomic association between multiple epistatically interacting loci in the host genome, and a family of genes encoding for collagen-like protein in the parasite genome. These findings are supported by laboratory-based infection trials, which show strong correspondence between phenotype and genotype at the identified loci. Our study provides clear genomic evidence of antagonistic co-evolution among wild populations.

Background MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression in organisms ranging from viruses to mammals. There is great relevance in understanding how miRNAs regulate genes involved in the growth, development, and maturation of the many parasitic worms (helminths) that together afflict more than 2 billion people. Results Here, we describe the miRNAs expressed by each of the predominant intra-mammalian development stages of Fasciola hepatica , a foodborne flatworm that infects a wide range of mammals worldwide, most importantly humans and their livestock. A total of 124 miRNAs were profiled, 72 of which had been previously reported and three of which were conserved miRNA sequences described here for the first time. The remaining 49 miRNAs were novel sequences of which, 31 were conserved with F. gigantica and the remaining 18 were specific to F. hepatica. The newly excysted juveniles express 22 unique miRNAs while the immature liver and mature bile duct stages each express 16 unique miRNAs. We discovered several sequence variant miRNAs (IsomiRs) as well as miRNA clusters that exhibit strict temporal expression paralleling parasite development. Target analysis revealed the close association between miRNA expression and stage-specific changes in the transcriptome; for example, we identified specific miRNAs that target parasite proteases known to be essential for intestinal wall penetration (cathepsin L3). Moreover, we demonstrate that miRNAs fine-tune the expression of genes involved in the metabolic pathways that allow the parasites to move from an aerobic external environment to the anerobic environment of the host. Conclusions These results provide novel insight into the regulation of helminth parasite development and identifies new genes and miRNAs for therapeutic development to limit the virulence and pathogenesis caused by F. hepatica .