Coevolution of Age-Structured Tolerance and Virulence.

Hosts can evolve a variety of defences against parasitism, including resistance (which prevents or reduces the spread of infection) and tolerance (which protects against virulence). Some organisms have evolved different levels of tolerance at different life-stages, which is likely to be the result of coevolution with pathogens, and yet it is currently unclear how coevolution drives patterns of age-specific tolerance. Here, we use a model of tolerance-virulence coevolution to investigate how age structure influences coevolutionary dynamics. Specifically, we explore how coevolution unfolds when tolerance and virulence (disease-induced mortality) are age-specific compared to when these traits are uniform across the host lifespan. We find that coevolutionary cycling is relatively common when host tolerance is age-specific, but cycling does not occur when tolerance is the same across all ages. We also find that age-structured tolerance can lead to selection for higher virulence in shorter-lived than in longer-lived hosts, whereas non-age-structured tolerance always leads virulence to increase with host lifespan. Our findings therefore suggest that age structure can have substantial qualitative impacts on host-pathogen coevolution.

Rapid bacteria-phage coevolution drives the emergence of multiscale networks.

Interactions between species catalyze the evolution of multiscale ecological networks, including both nested and modular elements that regulate the function of diverse communities. One common assumption is that such complex pattern formation requires spatial isolation or long evolutionary timescales. We show that multiscale network structure can evolve rapidly under simple ecological conditions without spatial structure. In just 21 days of laboratory coevolution, Escherichia coli and bacteriophage Φ21 coevolve and diversify to form elaborate cross-infection networks. By measuring ~10,000 phage-bacteria infections and testing the genetic basis of interactions, we identify the mechanisms that create each component of the multiscale pattern. Our results demonstrate how multiscale networks evolve in parasite-host systems, illustrating Darwin's idea that simple adaptive processes can generate entangled banks of ecological interactions.

Aspiration-driven co-evolution of cooperation with individual behavioral diversity.

In evolutionary game, aspiration-driven updates and imitation updates are the two dominant game models, and individual behavior patterns are mainly categorized into two types: node player and link player. In more recent studies, the mixture strategy of different types of players has been proven to improve cooperation substantially. Motivated by such a co-evolution mechanism, we combine aspiration dynamics with individual behavioral diversity, where self-assessed aspirations are used to update imitation strategies. In this study, the node players and the link players are capable to transform into each other autonomously, which introduces new features to cooperation in a diverse population as well. In addition, by driving all the players to form specific behavior patterns, the proposed mechanism achieves a survival environment optimization of the cooperators. As expected, the interaction between node players and link players allows the cooperator to avoid the invasion of the defector. Based on the experimental evaluation, the proposed work has demonstrated that the co-evolution mechanism has facilitated the emergence of cooperation by featuring mutual transformation between different players. We hope to inspire a new way of thinking for a promising solution to social dilemmas.

Molecular mechanisms of adaptive evolution in wild animals and plants.

Wild animals and plants have developed a variety of adaptive traits driven by adaptive evolution, an important strategy for species survival and persistence. Uncovering the molecular mechanisms of adaptive evolution is the key to understanding species diversification, phenotypic convergence, and inter-species interaction. As the genome sequences of more and more non-model organisms are becoming available, the focus of studies on molecular mechanisms of adaptive evolution has shifted from the candidate gene method to genetic mapping based on genome-wide scanning. In this study, we reviewed the latest research advances in wild animals and plants, focusing on adaptive traits, convergent evolution, and coevolution. Firstly, we focused on the adaptive evolution of morphological, behavioral, and physiological traits. Secondly, we reviewed the phenotypic convergences of life history traits and responding to environmental pressures, and the underlying molecular convergence mechanisms. Thirdly, we summarized the advances of coevolution, including the four main types: mutualism, parasitism, predation and competition. Overall, these latest advances greatly increase our understanding of the underlying molecular mechanisms for diverse adaptive traits and species interaction, demonstrating that the development of evolutionary biology has been greatly accelerated by multi-omics technologies. Finally, we highlighted the emerging trends and future prospects around the above three aspects of adaptive evolution.

Interactomics: Dozens of Viruses, Co-evolving With Humans, Including the Influenza A Virus, may Actively Distort Human Aging.

Some viruses (e.g., human immunodeficiency virus 1 and severe acute respiratory syndrome coronavirus 2) have been experimentally proposed to accelerate features of human aging and of cellular senescence. These observations, along with evolutionary considerations on viral fitness, raised the more general puzzling hypothesis that, beyond documented sources in human genetics, aging in our species may also depend on virally encoded interactions distorting our aging to the benefits of diverse viruses. Accordingly, we designed systematic network-based analyses of the human and viral protein interactomes, which unraveled dozens of viruses encoding proteins experimentally demonstrated to interact with proteins from pathways associated with human aging, including cellular senescence. We further corroborated our predictions that specific viruses interfere with human aging using published experimental evidence and transcriptomic data; identifying influenza A virus (subtype H1N1) as a major candidate age distorter, notably through manipulation of cellular senescence. By providing original evidence that viruses may convergently contribute to the evolution of numerous age-associated pathways through co-evolution, our network-based and bipartite network-based methodologies support an ecosystemic study of aging, also searching for genetic causes of aging outside a focal aging species. Our findings, predicting age distorters and targets for anti-aging therapies among human viruses, could have fundamental and practical implications for evolutionary biology, aging study, virology, medicine, and demography.

Coevolution of HTLV-1-HBZ, Tax, and proviral load with host IRF-1 and CCNA-2 in HAM/TSP patients.

Background HTLV-1-associated myelopathy (HAM/TSP) is a progressive neurodegenerative inflammatory condition of HTLV-1 infection. Viral-host interactions are a significant contributor to the symptoms of HTLV-1-associated diseases. Therefore, in this study, the expression of the main regulatory viral factors and proviral load (PVL) and two host transcription molecules were evaluated in HAM/TSP patients. Materials and methods The study population included 17 HAM/TSP patients, 20 asymptomatic carriers (ACs), and 19 healthy controls (HCs). RNA and DNA were extracted from PBMCs for assessment of the gene expressions and PVL assessment using RT-qPCR and TaqMan method. Results HTLV-1-PVL was higher in HAM/TSPs (395.80 ± 99.69) than ACs (92.92 ± 29.41) (P = 0.001). The Tax expression in HAM/TSPs (7.8 ± 5.7) was strongly higher than ACs (0.06 ± 0.04) (P = 0.02), while HTLV-1-HBZ was only increased around three times in HAM/TSPs (3.17), compared to ACs (1.20) and not significant. The host IRF1 expression in HAM/TSPs (0.4 ± 0.31) was higher than ACs (0.09 ± 0.05) (P = 0.02) and also HCs (0.16 ± 0.07) (P = 0.5), but lower in ACs than HCs (p = 0.01). Although, in HAM/TSPs (0.13 ± 0.09) and ACs (0.03 ± 0.02) CCNA-2 expression was statistically fewer than HCs (0.18 ± 0.06) (P = 0.03, P = 0.001, respectively), in HAM/TSP was higher than ACs (P = 0.1), but did not meet a 95% confidence interval. Conclusion The study showed that HTLV-1-PVL and Tax, along with host IRF-1, could be considered biomarkers in HAM/TSP development. Furthermore, IRF-1, as an essential transcription factor, can be considered a pivotal target in HAM/TSPs treatment.

The phylogenetic and evolutionary analyses of detoxification gene families in Aphidinae species.

Detoxification enzymes play significant roles in the interactions between insects and host plants, wherein detoxification-related genes make great contributions. As herbivorous pests, aphids reproduce rapidly due to parthenogenesis. They are good biological materials for studying the mechanisms that allow insect adaptation to host plants. Insect detoxification gene families are associated with insect adaptation to host plants. The Aphidinae is the largest subfamily in the Aphididae with at least 2483 species in 256 genera in 2 tribes: the Macrosiphini (with 3/4 of the species) and the Aphidini. Most aphid pests on crops and ornamental plants are Aphidinae. Members of the Aphidinae occur in nearly every region of the world. The body shape and colour vary significantly. To research the role that detoxification gene families played in the process of aphid adaptation to host evolution, we analyzed the phylogeny and evolution of these detoxification gene families in Aphidinae. In general, the P450/GST/CCE gene families contract, whereas the ABC/UGT families are conserved in Aphidinae species compared to these families in other herbivorous insects. Genus-specific expansions of P450 CYP4, and GST Delta have occurred in the genus Acyrthosiphon. In addition, the evolutionary rates of five detoxification gene families in the evolution process of Aphidinae are different. The comparison of five detoxification gene families among nine Aphidinae species and the estimated relative evolutionary rates provided herein support an understanding of the interaction between and the co-evolution of Aphidinae and plants.

Discovery and Evolutionary Analysis of a Novel Bat-Borne Paramyxovirus.

Paramyxoviruses are a group of RNA viruses, such as mumps virus, measles virus, Nipah virus, Hendra virus, Newcastle disease virus, and parainfluenza virus, usually transmitted by airborne droplets that are predominantly responsible for acute respiratory diseases. In this paper, we identified a novel paramyxovirus belonging to genus Jeilongvirus infecting 4/112 (3.6%) bats from two trapping sites of Hainan Province of China. In these animals, the viral RNA was detected exclusively in kidney tissues. This is the first full-length Jeilongvirus genome (18,095 nucleotides) from bats of genus Hipposideros, which exhibits a canonical genome organization and encodes SH and TM proteins. Results, based on phylogenic analysis and genetic distances, indicate that the novel paramyxovirus formed an independent lineage belonging to genus Jeilongvirus, representing, thus, a novel species. In addition, the virus-host macro-evolutionary analysis revealed that host-switching was not only a common co-phylogenetic event, but also a potential mechanism by which rats are infected by bat-origin Jeilongvirus through cross-species virus transmission, indicating a bat origin of the genus Jeilongvirus. Overall, our study broadens the viral diversity, geographical distribution, host range, and evolution of genus Jeilongvirus.

The legacy of the extinct Neotropical megafauna on plants and biomes.

Large mammal herbivores are important drivers of plant evolution and vegetation patterns, but the extent to which plant trait and ecosystem geography currently reflect the historical distribution of extinct megafauna is unknown. We address this question for South and Central America (Neotropical biogeographic realm) by compiling data on plant defence traits, climate, soil, and fire, as well as on the historical distribution of extinct megafauna and extant mammal herbivores. We show that historical mammal herbivory, especially by extinct megafauna, and soil fertility explain substantial variability in wood density, leaf size, spines and latex. We also identified three distinct regions (''antiherbiomes''), differing in plant defences, environmental conditions, and megafauna history. These patterns largely matched those observed in African ecosystems, where abundant megafauna still roams, and suggest that some ecoregions experienced savanna-to-forest shifts following megafauna extinctions. Here, we show that extinct megafauna left a significant imprint on current ecosystem biogeography.

Temporal specific coevolution of Hsp70 and co-chaperone stv expression in Drosophila melanogaster under selection for heat tolerance.

Heat shock proteins (Hsps) have long been candidates for ecological adaptation given their unequivocal role in mitigating cell damage from heat stress, but linking Hsps to heat tolerance has proven difficult given the complexity of thermal adaptation. Experimental evolution has been utilized to examine direct and correlated responses to selection for increased heat tolerance in Drosophila, often focusing on the major Hsp family Hsp70 and/or the master regulator HSF as a selection response, but rarely on other aspects of the heat shock complex. We examined Hsp70 and co-chaperone stv isoform transcript expression in Australian D. melanogaster lines selected for static heat tolerance, and observed a temporal and stv isoform specific, coordinated transcriptional selection response with Hsp70, suggesting that increased chaperone output accompanied increased heat tolerance. We hypothesize that the coordinated evolutionary response of Hsp70 and stv may have arisen as a correlated response resulting from a shared regulatory hierarchy. Our work highlights the complexity and specificity of the heat shock response in D. melanogaster. The selected lines examined also showed correlated responses for other measures of heat tolerance, and the coevolution of Hsp70 and stv provide new avenues to examine the common mechanisms underpinning direct and correlated phenotypic responses to selection for heat tolerance.

Inferring predator-prey interaction in the subterranean environment: a case study from Dinaric caves.

Predator-prey interactions are among the most important biotic interactions shaping ecological communities and driving the evolution of defensive traits. These interactions and their effects on species received little attention in extreme and remote environments, where possibilities for direct observations and experimental manipulation of the animals are limited. In this paper, we study such type of environment, namely caves of the Dinarides (Europe), combining spatial and phylogenetic methods. We focused on several species of Niphargus amphipods living in phreatic lakes, as some of them use the dorsal spines as putative morphological defensive traits. We predicted that these spines represent a defense strategy against the olm (Proteus anguinus), a top predator species in the subterranean waters. We tested for spatial overlap of the olm and Niphargus species and showed that spined species live in closer proximity to and co-occur more frequently with the olm than non-spined species. Modeling of the evolution of the spines onto Niphargus phylogeny implies coevolution of this trait in the presence of olm. We conclude that these spines likely evolved as defensive traits in a predator-prey arms race. Combining multiple analyses, we provide an example for a methodological framework to assess predator-prey interactions when in-situ or laboratory observations are not possible.

Neofunctionalization of an ancient domain allows parasites to avoid intraspecific competition by manipulating host behaviour.

Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite's manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system.

Complex evolutionary history of felid anelloviruses.

Anellovirus infections are highly prevalent in mammals, however, prior to this study only a handful of anellovirus genomes had been identified in members of the Felidae family. Here we characterise anelloviruses in pumas (Puma concolor), bobcats (Lynx rufus), Canada lynx (Lynx canadensis), caracals (Caracal caracal) and domestic cats (Felis catus). The complete anellovirus genomes (n = 220) recovered from 149 individuals were diverse. ORF1 protein sequence similarity network analysis coupled with phylogenetic analysis, revealed two distinct clusters that are populated by felid-derived anellovirus sequences, a pattern mirroring that observed for the porcine anelloviruses. Of the two-felid dominant anellovirus groups, one includes sequences from bobcats, pumas, domestic cats and an ocelot, and the other includes sequences from caracals, Canada lynx, domestic cats and pumas. Coinfections of diverse anelloviruses appear to be common among the felids. Evidence of recombination, both within and between felid-specific anellovirus groups, supports a long coevolution history between host and virus.

Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences.

Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second increases STA-2 levels in the nucleus, modifies the nucleolus, and, potentially as a consequence of a host surveillance mechanism, causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.

Bene"fit" Assessment in Pollination Coevolution: Mechanistic Perspectives on Hummingbird Bill-Flower Matching.

One of the reasons why flowering plants became the most diverse group of land plants is their association with animals to reproduce. The earliest examples of this mutualism involved insects foraging for food from plants and, in the process, pollinating them. Vertebrates are latecomers to these mutualisms, but birds, in particular, present a wide variety of nectar-feeding clades that have adapted to solve similar challenges. Such challenges include surviving on small caloric rewards widely scattered across the landscape, matching their foraging strategy to nectar replenishment rate, and efficiently collecting this liquid food from well-protected chambers deep inside flowers. One particular set of convergent traits among plants and their bird pollinators has been especially well studied: the match between the shape and size of bird bills and ornithophilous flowers. Focusing on a highly specialized group, hummingbirds, we examine the expected benefits from bill-flower matching, with a strong focus on the benefits to the hummingbird and how to quantify them. Explanations for the coevolution of bill-flower matching include (1) that the evolution of traits by bird-pollinated plants, such as long and thin corollas, prevents less efficient pollinators (e.g., insects) from accessing the nectar and (2) that increased matching, as a result of reciprocal adaptation, benefits both the bird (nectar extraction efficiency) and the plant (pollen transfer). In addition to nectar-feeding, we discuss how interference and exploitative competition also play a significant role in the evolution and maintenance of trait matching. We present hummingbird-plant interactions as a model system to understand how trait matching evolves and how pollinator behavior can modify expectations based solely on morphological matching, and discuss the implications of this behavioral modulation for the maintenance of specialization. While this perspective piece directly concerns hummingbird-plant interactions, the implications are much broader. Functional trait matching is likely common in coevolutionary interactions (e.g., in predator-prey interactions), yet the physical mechanisms underlying trait matching are understudied and rarely quantified. We summarize existing methods and present novel approaches that can be used to quantify key benefits to interacting partners in a variety of ecological systems.

The private life of malaria parasites: Strategies for sexual reproduction.

Malaria parasites exhibit a complex lifecycle, requiring extensive asexual replication in the liver and blood of the vertebrate host, and in the haemocoel of the insect vector. Yet, they must also undergo a single round of sexual reproduction, which occurs in the vector's midgut upon uptake of a blood meal. Sexual reproduction is obligate for infection of the vector and thus, is essential for onwards transmission to new hosts. Sex in malaria parasites involves several bottlenecks in parasite number, making the stages involved attractive targets for blocking disease transmission. Malaria parasites have evolved a suite of adaptations ("strategies") to maximise the success of sexual reproduction and transmission, which could undermine transmission-blocking interventions. Yet, understanding parasite strategies may also reveal novel opportunities for such interventions. Here, we outline how evolutionary and ecological theories, developed to explain reproductive strategies in multicellular taxa, can be applied to explain two reproductive strategies (conversion rate and sex ratio) expressed by malaria parasites within the vertebrate host.

Is the ZIKV Congenital Syndrome and Microcephaly Due to Syndemism with Latent Virus Coinfection?

The emergence of the Zika virus (ZIKV) mirrors its evolutionary nature and, thus, its ability to grow in diversity or complexity (i.e., related to genome, host response, environment changes, tropism, and pathogenicity), leading to it recently joining the circle of closed congenital pathogens. The causal relation of ZIKV to microcephaly is still a much-debated issue. The identification of outbreak foci being in certain endemic urban areas characterized by a high-density population emphasizes that mixed infections might spearhead the recent appearance of a wide range of diseases that were initially attributed to ZIKV. Globally, such coinfections may have both positive and negative effects on viral replication, tropism, host response, and the viral genome. In other words, the possibility of coinfection may necessitate revisiting what is considered to be known regarding the pathogenesis and epidemiology of ZIKV diseases. ZIKV viral coinfections are already being reported with other arboviruses (e.g., chikungunya virus (CHIKV) and dengue virus (DENV)) as well as congenital pathogens (e.g., human immunodeficiency virus (HIV) and cytomegalovirus (HCMV)). However, descriptions of human latent viruses and their impacts on ZIKV disease outcomes in hosts are currently lacking. This review proposes to select some interesting human latent viruses (i.e., herpes simplex virus 2 (HSV-2), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), human parvovirus B19 (B19V), and human papillomavirus (HPV)), whose virological features and co-exposition with ZIKV may provide evidence of the syndemism process, shedding some light on the emergence of the ZIKV-induced global congenital syndrome in South America.

Cardenolides, toxicity, and the costs of sequestration in the coevolutionary interaction between monarchs and milkweeds.

For highly specialized insect herbivores, plant chemical defenses are often co-opted as cues for oviposition and sequestration. In such interactions, can plants evolve novel defenses, pushing herbivores to trade off benefits of specialization with costs of coping with toxins? We tested how variation in milkweed toxins (cardenolides) impacted monarch butterfly (Danaus plexippus) growth, sequestration, and oviposition when consuming tropical milkweed (Asclepias curassavica), one of two critical host plants worldwide. The most abundant leaf toxin, highly apolar and thiazolidine ring-containing voruscharin, accounted for 40% of leaf cardenolides, negatively predicted caterpillar growth, and was not sequestered. Using whole plants and purified voruscharin, we show that monarch caterpillars convert voruscharin to calotropin and calactin in vivo, imposing a burden on growth. As shown by in vitro experiments, this conversion is facilitated by temperature and alkaline pH. We next employed toxin-target site experiments with isolated cardenolides and the monarch's neural Na+/K+-ATPase, revealing that voruscharin is highly inhibitory compared with several standards and sequestered cardenolides. The monarch's typical >50-fold enhanced resistance to cardenolides compared with sensitive animals was absent for voruscharin, suggesting highly specific plant defense. Finally, oviposition was greatest on intermediate cardenolide plants, supporting the notion of a trade-off between benefits and costs of sequestration for this highly specialized herbivore. There is apparently ample opportunity for continued coevolution between monarchs and milkweeds, although the diffuse nature of the interaction, due to migration and interaction with multiple milkweeds, may limit the ability of monarchs to counteradapt.

Coevolution underlies GPCR-G protein selectivity and functionality.

G protein-coupled receptors (GPCRs) regulate diverse physiological events, which makes them as the major targets for many approved drugs. G proteins are downstream molecules that receive signals from GPCRs and trigger cell responses. The GPCR-G protein selectivity mechanism on how they properly and timely interact is still unclear. Here, we analyzed model GPCRs (i.e. HTR, DAR) and Gα proteins with a coevolutionary tool, statistical coupling analysis. The results suggested that 5-hydroxytryptamine receptors and dopamine receptors have common conserved and coevolved residues. The Gα protein also have conserved and coevolved residues. These coevolved residues were implicated in the molecular functions of the analyzed proteins. We also found specific coevolving pairs related to the selectivity between GPCR and G protein were identified. We propose that these results would contribute to better understandings of not only the functional residues of GPCRs and Gα proteins but also GPCR-G protein selectivity mechanisms.

Trivial and nontrivial error sources account for misidentification of protein partners in mutual information approaches.

The problem of finding the correct set of partners for a given pair of interacting protein families based on multi-sequence alignments (MSAs) has received great attention over the years. Recently, the native contacts of two interacting proteins were shown to store the strongest mutual information (MI) signal to discriminate MSA concatenations with the largest fraction of correct pairings. Although that signal might be of practical relevance in the search for an effective heuristic to solve the problem, the number of MSA concatenations with near-native MI is large, imposing severe limitations. Here, a Genetic Algorithm that explores possible MSA concatenations according to a MI maximization criteria is shown to find degenerate solutions with two error sources, arising from mismatches among (i) similar and (ii) non-similar sequences. If mistakes made among similar sequences are disregarded, type-(i) solutions are found to resolve correct pairings at best true positive (TP) rates of 70%-far above the very same estimates in type-(ii) solutions. A machine learning classification algorithm helps to show further that differences between optimized solutions based on TP rates are not artificial and may have biological meaning associated with the three-dimensional distribution of the MI signal. Type-(i) solutions may therefore correspond to reliable results for predictive purposes, found here to be more likely obtained via MI maximization across protein systems having a minimum critical number of amino acid contacts on their interaction surfaces (N > 200).