Yearlong COVID-19 Infection Reveals Within-Host Evolution of SARS-CoV-2 in a Patient With B-Cell Depletion.

B-cell-depleting therapies may lead to prolonged disease and viral shedding in individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this viral persistence raises concern for viral evolution. We report sequencing of early and late samples from a 335-day infection in an immunocompromised patient. The virus accumulated a unique deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts.

Ecological mechanism of climate-mediated selection in a rapidly evolving invasive species.

Recurring seasonal changes can lead to the evolution of phenological cues. For example, many arthropods undergo photoperiodic diapause, a programmed developmental arrest induced by short autumnal day length. The selective mechanisms that determine the timing of autumnal diapause initiation have not been empirically identified. We quantified latitudinal clines in genetically determined diapause timing of an invasive mosquito, Aedes albopictus, on two continents. We show that variation in diapause timing within and between continents is explained by a novel application of a growing degree day (GDD) model that delineates a location-specific deadline after which it is not possible to complete an additional full life cycle. GDD models are widely used to predict spring phenology by modelling growth and development as physiological responses to ambient temperatures. Our results show that the energy accumulation dynamics represented by GDD models have also led to the evolution of an anticipatory life-history cue in autumn.

Environmental Sources of Bacteria and Genetic Variation in Behavior Influence Host-Associated Microbiota.

In many organisms, host-associated microbial communities are acquired horizontally after birth. This process is believed to be shaped by a combination of environmental and host genetic factors. We examined whether genetic variation in animal behavior could affect the composition of the animal's microbiota in different environments. The freshwater crustacean Daphnia magna is primarily planktonic but exhibits variation in the degree to which it browses in benthic sediments. We performed an experiment with clonal lines of D. magna showing different levels of sediment-browsing intensity exposed to either bacteria-rich or bacteria-poor sediment or whose access to sediments was prevented. We found that the bacterial composition of the environment and genotype-specific browsing intensity together influence the composition of the Daphnia-associated bacterial community. Exposure to more diverse bacteria did not lead to a more diverse microbiome, but greater abundances of environment-specific bacteria were found associated with host genotypes that exhibited greater browsing behavior. Our results indicate that, although there is a great deal of variation between individuals, behavior can mediate genotype-by-environment interaction effects on microbiome composition.IMPORTANCE An animal's behavior can affect its risk of infection, but it is not well understood how behavior affects microbiome composition. The aquatic crustacean Daphnia exhibits genetic variation in the extent to which it browses in the sediment at the bottoms of ponds. We show that this behavior affects the Daphnia microbiome, indicating that genetic variation among individuals may affect microbiome composition and the movement of bacteria in different environments.

The microbiota of diapause: How host-microbe associations are formed after dormancy in an aquatic crustacean.

A critical question in symbiosis research is where and how organisms obtain beneficial microbial symbionts in different ecological contexts. Microbiota of juveniles are often derived directly from their mother or from the immediate environment. The origin of beneficial symbionts, however, is less obvious in organisms with diapause and dispersal stages, such as plants with dormant seeds and animals in ephemeral or strongly seasonal habitats. In these cases, parents and offspring are separated in time and space, which may affect opportunities for both vertical and horizontal transmission of symbionts. The planktonic crustacean Daphnia produces long-lasting resting eggs to endure winter freezing and summer droughts and requires microbiota for growth and reproduction. It is unknown how hatchlings from resting stages form associations with microbial consorts after diapause. Using natural samples of D. magna resting eggs after several years of storage, we show that the total bacterial community derived from both the exterior and interior of the eggs' ephippial cases is sufficiently beneficial to ensure normal Daphnia functioning in otherwise bacteria-free conditions. We do not find direct evidence that the required bacteria are of maternal origin, though sequencing reveals that the resting stage is accompanied by bacterial taxa previously found in association with adult animals. These findings suggest that although Daphnia are strongly dependent on environmental bacteria for normal functioning, host-bacteria associations are somewhat general and availability of specific bacteria is not a strong constraint on host ecology. Nevertheless, animals and microbes may be ecologically linked through co-dispersal.

Rethinking "mutualism" in diverse host-symbiont communities.

While examples of bacteria benefiting eukaryotes are increasingly documented, studies examining effects of eukaryote hosts on microbial fitness are rare. Beneficial bacteria are often called "mutualistic" even if mutual reciprocity of benefits has not been demonstrated and despite the plausibility of other explanations for these microbes' beneficial effects on host fitness. Furthermore, beneficial bacteria often occur in diverse communities, making mutualism both empirically and conceptually difficult to demonstrate. We suggest reserving the terms "mutualism" and "parasitism" for pairwise interactions where the relationship is largely independent of other species and can be verified by measuring the fitness effect experienced by both partners. In hosts with diverse microbial communities, we propose re-formulating some of the essential questions of symbiosis research - e.g. concerning specificity, transmission mode, and common evolutionary fates - as questions of community ecology and ecosystem function, allowing important biological interactions to be investigated without making assumptions about reciprocity. Understanding the fitness of host-associated bacteria is a crucial component of investigations into the role of microbes in eukaryote evolution.

Temperature-dependent benefits of bacterial exposure in embryonic development of Daphnia magna resting eggs.

The environments in which animals develop and evolve are profoundly shaped by bacteria, which affect animals both indirectly through their role in biogeochemical processes and directly through antagonistic or beneficial interactions. The outcomes of these activities can differ according to environmental context. In a series of laboratory experiments with diapausing eggs of the water flea Daphnia magna, we manipulated two environmental parameters, temperature and presence of bacteria, and examined their effect on development. At elevated temperatures (≥ 26 °C), resting eggs developing without live bacteria had reduced hatching success and correspondingly higher rates of severe morphological abnormalities compared with eggs with bacteria in their environment. The beneficial effect of bacteria was strongly reduced at 20 °C. Neither temperature nor the presence of bacteria affected directly developing parthenogenetic eggs. The mechanistic basis of this effect of bacteria on development is unclear, but these results highlight the complex interplay of biotic and abiotic factors influencing animal development after diapause.

Unidirectional evolutionary transitions in fungal mating systems and the role of transposable elements.

In the fungal kingdom, the evolution of mating systems is highly dynamic, varying even among closely related species. Rearrangements in the mating-type (mat) locus, which contains the major regulators of sexual development, are expected to underlie the transitions between self-sterility (heterothallism) and self-fertility (homothallism). However, both the genetic mechanisms and the direction of evolutionary transitions in fungal mating systems are under debate. Here, we present new sequences of the mat locus of four homothallic and one heterothallic species of the model genus Neurospora (Ascomycota). By examining the patterns of synteny among these sequences and previously published data, we show that the locus is conserved among heterothallic species belonging to distinct phylogenetic clades, while different gene arrangements characterize the four homothallic species. These results allowed us to ascertain a heterothallic ancestor for the genus, confirming the prediction of the dead-end theory on unidirectional transitions toward selfing. We show that at least four shifts from heterothallism to homothallism have occurred in Neurospora, three of which involve the acquisition of sequences of both mating types into the same haploid genome. We present evidence for two genetic mechanisms allowing these shifts: translocation and unequal crossover. Finally, we identified two novel retrotransposons and suggest that these have played a major role in mating-system transitions, by facilitating multiple rearrangements of the mat locus.

Within-host genetic diversity of SARS-CoV-2 in the context of large-scale hospital-associated genomic surveillance.

The COVID-19 pandemic has resulted in extensive surveillance of the genomic diversity of SARS-CoV-2. Sequencing data generated as part of these efforts can also capture the diversity of the SARS-CoV-2 virus populations replicating within infected individuals. To assess this within-host diversity of SARS-CoV-2 we quantified low frequency (minor) variants from deep sequence data of thousands of clinical samples collected by a large urban hospital system over the course of a year. Using a robust analytical pipeline to control for technical artefacts, we observe that at comparable viral loads, specimens from patients hospitalized due to COVID-19 had a greater number of minor variants than samples from outpatients. Since individuals with highly diverse viral populations could be disproportionate drivers of new viral lineages in the patient population, these results suggest that transmission control should pay special attention to patients with severe or protracted disease to prevent the spread of novel variants.

Bacterial diversity across individual lichens.

Symbioses are unique habitats for bacteria. We surveyed the spatial diversity of bacterial communities across multiple individuals of closely related lichens using terminal restriction fragment length polymorphism (T-RFLP) and pyrosequencing. Centers of lichens house richer, more consistent assemblages than species-poor and compositionally disparate lichen edges, suggesting that ecological succession plays a role in structuring these communities.

Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion.

BACKGROUND: B-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution. METHODS: Amplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs. Whole genome sequencing was performed on samples from the patient's original presentation and 10 months later. RESULTS: Over the course of almost a year, the virus accumulated a unique in-frame deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Also, minority variants that were identified in the early samples-reflecting the heterogeneity of the initial infection-were found to be fixed late in the infection. Remdesivir and high-titer convalescent plasma treatment were given, and the infection was eventually cleared after 335 days of infection. CONCLUSIONS: The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants. SUMMARY: We report an immunocompromised patient with persistent symptomatic SARS-CoV-2 infection for 335 days. During this time, the virus accumulated a unique in-frame deletion in the spike, and a complete deletion of ORF7b and ORF8 which is the first report of its kind in an immunocompromised patient.

Animal-Microbe Interactions in the Context of Diapause.

Dormancy and diapause are key adaptations in many organisms, enabling survival of temporarily or seasonally unsuitable environmental conditions. In this review, we examine how our understanding of programmed developmental and metabolic arrest during diapause intersects with the increasing body of knowledge about animal co-development and co-evolution with microorganisms. Host-microbe interactions are increasingly understood to affect a number of metabolic, physiological, developmental, and behavioral traits and to mediate adaptations to various environments. Therefore, it is timely to consider how microbial factors might affect the expression and evolution of diapause in a changing world. We examine how a range of host-microbe interactions, from pathogenic to mutualistic, may have an impact on diapause phenotypes. Conversely, we examine how the discontinuities that diapause introduces into animal host generations can affect the ecology of microbial communities and the evolution of host-microbe interactions. We discuss these issues as they relate to physiology, evolution of development, local adaptation, disease ecology, and environmental change. Finally, we outline research questions that bridge the historically distinct fields of seasonal ecology and host-microbe interactions.

UV radiation induces a gene's dual functionality.

A protein and noncoding RNA encoded by the same gene have opposing roles in the response to UV radiation-induced damage.

Guanidine throws the riboswitch.

A bacterial riboswitch responds to endogenously produced guanidine.

Microbiome-dependent recombination shapes the host antibody repertoire.

Secreted IgD concentration depends on the presence of microbiota.

Sources of variation: Animal microbiota.

The diverse effects of microbiota on animal physiology contribute to experimental variability.

Ferroptosis-like cell death in plants.

Heat stress induces a form of cell death in plants that is morphologically and biochemically similar to ferroptosis in animal cells.

When silencing mRNA, position matters.

The mechanism of posttranscriptional silencing by an RNA-binding protein depends on the position of the protein-binding sequence in the mRNA.

Recovering rRNA processing after heat shock.

NF-κB repressing factor controls localization and activation of an rRNA processing protein in heat stress response.

Autophagy and vitamin D.

Vitamin D receptor represses basal autophagy in breast tissue, which is derepressed by vitamin D, slowing cancer progression.

NLS protects DNA damage protein.

A single motif targets a protein to the nucleus and directs its deubiquitylation, promoting high-fidelity DNA damage repair.