BMC Biology最新文献

Background: Early in the coronavirus disease 2019 (COVID-19) pandemic, Sunda pangolins (Manis javanica) involved in the illegal wildlife trade in mainland China were identified as hosts of severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Although it is unconfirmed whether pangolins or other traded wildlife served as intermediate hosts for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the trafficking of pangolins presents a clear risk for transmission of viruses with zoonotic and epizootic potential regardless. We have investigated the origins of pangolin carcasses seized in Hong Kong and have evaluated their potential exposure to SARSr-CoVs, other coronaviruses, and paramyxoviruses, aiming to address a gap in our knowledge with regard to the role of wildlife trade in the maintenance and emergence of pathogens with zoonotic and epizootic potential.

Results: Using a combination of virological and wildlife forensics tools, we investigated 89 Sunda pangolin carcasses seized by Hong Kong authorities during anti-smuggling operations in the territory conducted in 2013 (n = 1) and 2018 (n = 88). Swabs, organ tissues, blood, and other body fluids were collected during post-mortem examination. Two enzyme-linked immunosorbent assays (ELISAs), which employ a double-antigen sandwich format, were used to detect antibodies reactive against SARSr-CoVs. One individual was found to be seropositive with support from both methods, while five individuals exhibited a putatively seropositive result from one ELISA method. Polymerase chain reaction (PCR) screening for coronavirus and paramyxovirus ribonucleic acid (RNA) did not yield any positives. Based on genomic data, the seropositive individual was determined to have likely originated from Java, while the putatively seropositive individuals were determined to have originated from populations in Borneo, Java, and Singapore/Sumatra.

Conclusions: While the role of pangolins in the evolution and ecology of SARS-CoV-2 is uncertain, our results suggest susceptibility and potential exposure of pangolins to SARSr-CoVs, occurring naturally or associated with the illegal trafficking of these animals. Complex dynamics between natural populations, traded individuals, and pathogen susceptibility complicate conclusions about the role of pangolins, as well as other host species, in the ecology of SARSr-CoVs and potentially zoonotic viruses with risk of future emergence.

Background: Extinct organisms provide vital information about the time of origination and biogeography of extant groups. The development of phylogenetic methods to study evolutionary processes through time has revolutionized the field of evolutionary biology and led to an unprecedented expansion of our knowledge of the tree of life. Recent developments applying Bayesian approaches, using fossil taxa as tips to be included alongside their living relatives, have revitalized the use of morphological data in evolutionary tree inferences. Eumuroida rodents represent the largest group of mammals including more than a quarter of all extant mammals and have a rich fossil record spanning the last ~ 45 million years. Despite this wealth of data, our current understanding of the classification, major biogeographic patterns, and divergence times for this group comes from molecular phylogenies that use fossils only as a source of node calibrations. However, node calibrations impose several constraints on tree topology and must necessarily make a priori assumptions about the placement of fossil taxa without testing their placement in the tree.

Results: We present the first morphological dataset with extensive fossil sampling for Muroidea. By applying Bayesian morphological clocks with tip dating and process-based biogeographic models, we provide a novel hypothesis for muroid relationships and revised divergence times for the clade that incorporates uncertainty in the placement of all fossil species. Even under strong violation of the clock model, we found strong congruence between results for divergence times, providing a robust timeline for muroid diversification. This new timeline was used for biogeographic analyses, which revealed a dynamic scenario mostly explained by dispersal events between and within the Palearctic and North African regions.

Conclusions: Our results provide important insights into the evolution of Muroidea rodents and clarify the evolutionary pathways of their main lineages. We exploited the advantage of tip dating Bayesian approaches in morphology-based datasets and provided a classification of the largest superfamily of mammals resulting from robust phylogenetic inference, inferring the biogeographical history, diversification, and divergence times of its major lineages.

Background: It is generally accepted that nuclear genes in eukaryotes are located independently on chromosomes and expressed in a monocistronic manner. However, accumulating evidence suggests a more complex landscape of gene structure and transcription. Ganoderma lingzhi, a model medicinal fungus, currently lacks high-quality genome annotation, hindering genetic studies.

Results: Here, we reported a golden annotation of G. lingzhi, featuring 14,147 high-confidence genes derived from extensive manual corrections. Novel characteristics of gene structure and transcription were identified accordingly. Notably, non-canonical splicing sites accounted for 1.99% of the whole genome, with the predominant types being GC-AG (1.85%), GT-AC (0.05%), and GT-GG (0.04%). 1165 pairs of genes were found to have overlapped transcribed regions, and 92.19% of which showed opposite directions of gene transcription. A total of 5,412,158 genetic variations were identified among 13 G. lingzhi strains, and the manually corrected gene sets resulted in enhanced functional annotation of these variations. More than 60% of G. lingzhi genes were alternatively spliced. In addition, we found that two or more protein-coding genes (PCGs) can be transcribed into a single RNA molecule, referred to as polycistronic genes. In total, 1272 polycistronic genes associated with 2815 PCGs were identified.

Conclusions: The widespread presence of polycistronic genes in G. lingzhi strongly complements the theory that polycistron is also present in eukaryotic genomes. The extraordinary gene structure and transcriptional activity uncovered through this golden annotation provide implications for the study of genes, genomes, and related studies in G. lingzhi and other eukaryotes.

Background: Understanding how ectotherms manage energy in response to temperature is crucial for predicting their responses to climate change. However, the complex interplay between developmental and adult thermal conditions on total energy stores remains poorly understood. Here, we present the first comprehensive quantification of this relationship in Drosophila melanogaster, a model ectotherm, across its entire thermal tolerance range. To account for potential intraspecific variation, we used flies from two distinct populations originating from different climate zones. Utilizing a full factorial design, we assessed the effects of both developmental and adult temperatures on the amount of key energy macromolecules (fat, glycogen, trehalose, and glucose). Importantly, by quantifying these macromolecules, we were able to calculate the total available energy.

Results: Our findings reveal that the dynamic interplay between developmental and adult temperatures profoundly influences the energy balance in Drosophila. The total energy reserves exhibited a quadratic response to adult temperature, with an optimal range of 18-21 °C for maximizing energy levels. Additionally, the temperature during development considerably affected maximum energy stores, with the highest reserves observed at a developmental temperature of approximately 20-21 °C. Deviations from this relatively narrow optimal thermal range markedly reduced energy stores, with each 1 °C increase above 25 °C diminishing energy reserves by approximately 15%.

Conclusions: This study highlights the critical and interacting roles of both developmental and adult thermal conditions in shaping Drosophila energy reserves, with potentially profound implications for fitness, survival, and ecological interactions under future climate scenarios.

Background: Wolbachia incompatible insect technique (IIT) programs have been shown in field trials to be highly effective in suppressing populations of mosquitoes that carry diseases such as dengue, chikungunya, and Zika. However, the frequent and repeated release of Wolbachia-infected male mosquitoes makes such programs resource-intensive. While the need for optimization is recognized, potential strategies to optimize releases and reduce resource utilization have not been fully explored.

Results: We developed a process-based model to study the spatio-temporal metapopulation dynamics of mosquitoes in a Wolbachia IIT program, which explicitly incorporates climatic influence in mosquito life-history traits. We then used the model to simulate various scale-down and redistribution strategies to optimize the existing program in Singapore. Specifically, the model was used to study the trade-offs between the intervention efficacy outcomes and resource requirements of various release program strategies, such as the total number of release events and the number of mosquitoes released. We found that scaling down releases in existing sites from twice a week to only once a week yielded small changes in suppression efficacy (from 87 to 80%), while requiring 44% fewer mosquitoes and release events. Additionally, redistributing mosquitoes from already suppressed areas and releasing them in new areas once a week led to a greater total suppressive efficacy (83% compared to 61%) while also yielding a 16% and 14% reduction in the number of mosquitoes and release events required, respectively.

Conclusions: Both scale-down and redistribution strategies can be implemented to significantly reduce program resource requirements without compromising the suppressive efficacy of IIT. These findings will inform planners on ways to optimize existing and future IIT programs, potentially allowing for the wider adoption of this method for mosquito-borne disease control.

Background: Ancient Chang'an in the Tang Dynasty (618-907 AD) was one of the world's largest and most populated cities and acted as the eastern end of the world-famous Silk Road. However, little is known about the genetics of Chang'an people and whether the Western Regions-related gene flows have been prevalent in this cosmopolitan city.

Results: Here, we present seven genomes from Xingfulindai (XFLD) sites dating to the Tang Dynasty in Chang'an. We observed that four of seven XFLD individuals (XFLD_1) were genetically homogenous with the Late Neolithic Wadian, Pingliangtai, and Haojiatai populations from the middle reaches of the Yellow River Basin (YR_LN), with no genetic influence from the Western Eurasian or other non-Yellow River-related lineages. The remaining three XFLD individuals were a mixture of YR_LN-related ancestry and ~ 3-15% Western Eurasian-related ancestry. Mixtures of XFLD_1 and Western Eurasian-related ancestry drove the main gradient of genetic variation in northern and central Shaanxi Province today.

Conclusions: Our study underlined the widespread distribution of the YR_LN-related ancestry alongside the Silk Road within the territory of China during the historical era and provided direct evidence of trans-Eurasian communication in Chang'an from a genetic perspective.

Background: Insects detect odours using odorant receptors (ORs) expressed in olfactory sensory neurons (OSNs) in the antennae. Ecologically important odours are often detected by selective and abundant OSNs; hence, ORs with high antennal expression. However, little is known about the function of highly expressed ORs in beetles, since few ORs have been functionally characterized. Here, we functionally characterized the most highly expressed OR (ItypOR36) in the bark beetle Ips typographus L. (Coleoptera, Curculionidae, Scolytinae), a major pest of spruce. We hypothesized that this OR would detect a compound important to beetle fitness, such as a pheromone component. We next investigated the antennal distribution of this OR using single sensillum recordings (SSR) and in situ hybridization, followed by field- and laboratory experiments to evaluate the behavioural effects of the discovered ligand.

Results: We expressed ItypOR36 in HEK293 cells and challenged it with 64 ecologically relevant odours. The OR responded exclusively to the monoterpene-derived ketone lanierone with high sensitivity. Lanierone is used in chemical communication in North American Ips species, but it has never been shown to be produced by I. typographus, nor has it been studied in relation to this species' sensory physiology. Single sensillum recordings revealed a novel and abundant lanierone-responsive OSN class with the same specific response as ItypOR36. Strikingly, these OSNs were co-localized in sensilla together with seven different previously described OSN classes. Field experiments revealed that low release rates of lanierone inhibited beetle attraction to traps baited with aggregation pheromone, with strongest effects on males. Female beetles were attracted to lanierone in laboratory walking bioassays.

Conclusions: Our study highlights the importance of the so-called 'reverse chemical ecology' approach to identify novel semiochemicals for ecologically important insect species. Our discovery of the co-localization pattern involving the lanierone OSN class suggests organizational differences in the peripheral olfactory sense between insect orders. Our behavioural experiments show that lanierone elicits different responses in the two sexes, which also depend on whether beetles are walking in the laboratory or flying in the field. Unravelling the source of lanierone in the natural environment of I. typographus is required to understand these context-dependent behaviours.

Background: Dietary restriction (DR) has multiple beneficial effects on health and longevity and can also improve the efficacy of certain therapies. Diets used to instigate DR are diverse and the corresponding response is not uniformly measured. We compared the systemic and liver-specific transcriptional response to intermittent fasting (IF) and commercially available fasting-mimicking diet (FMD) after short- and long-term use in C57BL/6 J mice.

Results: We show that neither DR regimen causes observable adverse effects in mice. The weight loss was limited to 20% and was quickly compensated during refeeding days. The slightly higher weight loss upon FMD versus IF correlated with stronger fasting response assessed by lower glucose levels and higher ketone body, free fatty acids and especially FGF21 concentrations in blood. RNA sequencing demonstrated similar transcriptional programs in the liver after both regimens, with PPARα signalling as top enriched pathway, while on individual gene level FMD more potently increased gluconeogenesis-related, and PPARα and p53 target gene expression compared to IF. Repeated IF induced similar transcriptional responses as acute IF. However, repeated cycles of FMD resulted in blunted expression of genes involved in ketogenesis and fatty acid oxidation.

Conclusions: Short-term FMD causes more pronounced changes in blood parameters and slightly higher weight loss than IF, while both activate similar pathways (particularly PPARα signalling) in the liver. On individual gene level FMD induces a stronger transcriptional response, whereas cyclic application blunts transcriptional upregulation of fatty acid oxidation and ketogenesis only in FMD. Hence, our comparative characterization of IF and FMD protocols renders both as effective DR regimens and serves as resource in the fasting research field.

Background: The fungal phytopathogen Zymoseptoria tritici, causal agent of the economically damaging Septoria tritici blotch of wheat, is different from most foliar fungal pathogens in that its germination occurs slowly and apparently randomly after arrival on the leaf surface and is followed by a potentially prolonged period of epiphytic growth and even reproduction, during which no feeding structures are formed by the fungus. Thus, understanding the cues for germination and the mechanisms that underpin survival in low-nutrient environments could provide key new avenues for disease control.

Results: In this work, we examine survival, culturability and virulence of spores following transfer from a high nutrient environment to water. We find that a sub-population of Z. tritici spores can survive and remain virulent for at least 7 weeks in water alone, during which time multicellular structures split to single cells. The fungus relies heavily on stored lipids; however, if cell suspensions in water are dried, the cells survive without lipid utilisation. Changes in gene expression in the first hours after suspension in water reflect adaptation to stress, while longer term starvation (7 days) induces changes particularly in primary metabolism and cytochrome P450 (CYP) gene expression. Importantly, we also found that Z. tritici spores are equally or better able to survive in soil as in water, and that rain-splash occurring 49 days after soil inoculation can transfer cells to wheat seedlings growing in inoculated soil and cause Septoria leaf blotch disease.

Conclusions: Z. tritici blastospores can survive in water or soil for long periods, potentially spanning the intercrop period for UK winter wheat. They rely on internal lipid stores, with no external nutrition, and although a large proportion of spores do not survive for such an extended period, those that do remain as virulent as spores grown on rich media. Thus, Z. tritici has exceptional survival strategies, which are likely to be important in understanding its population genetics and in developing novel routes for Septoria leaf blotch control.

Background: For decades, KRAS has always been a huge challenge to the field of drug discovery for its significance in cancer progression as well as its difficulties in being targeted as an "undruggable" protein. KRAS regulates downstream signaling pathways through protein-protein interactions, whereas many interaction partners of KRAS remain unknown.

Results: We developed a workflow to computationally predict and experimentally validate the potential KRAS-interacting proteins based on the interaction mode of KRAS and its known binding partners. We extracted 17 KRAS-interacting motifs from all experimentally determined KRAS-containing protein complexes as queries to identify proteins containing fragments structurally similar to the queries in the human protein structure database using our in-house protein-protein interaction prediction method, PPI-Miner. Finally, out of the 78 predicted potential interacting proteins of KRAS, 10 were selected for experimental validation, including BRAF, a previously reported interacting protein, which served as the positive control in our validation experiments. Additionally, a known peptide that binds to KRAS, KRpep-2d, was also used as a positive control. The predicted interacting motifs of these 10 proteins were synthesized to perform biolayer interferometry assays, with 4 out of 10 exhibiting binding affinities to KRAS, and the strongest, GRB10, was selected for further validation. Additionally, the interaction between GRB10 (RA-PH domain) and KRAS was confirmed via immunofluorescence and co-immunoprecipitation.

Conclusions: These results demonstrate the effectiveness of our workflow in predicting potential interacting proteins for KRAS and deepen the understanding of KRAS-driven tumor mechanisms and the development of therapeutic strategies.