BMC Biology最新文献

Background: RNA interference (RNAi), a naturally occurring gene silencing mechanism found in almost all eukaryotic organisms, has proven to be an adaptable and powerful tool in therapeutics, bioengineering, and agriculture. Differential responses to RNAi, however, are a key limiting factor, in which cellular uptake of exogenous dsRNA in target organisms remains poorly understood.

Results: Here, to fill this knowledge gap, we integrated omics tools with phenotypic assays to characterize dsRNA uptake mechanisms across tissues in the migratory locust, Locusta migratoria (Orthoptera). Our findings clearly demonstrate that cellular uptake of dsRNA is tissue-dependent, involving multiple cell membrane receptors and pathways. In hemocytes, uptake is rapid and mediated by clathrin-mediated endocytosis and macropinocytosis. Epidermal cells utilize clathrin- and caveolin-mediated endocytosis, while midgut cells employ caveolin-mediated endocytosis and Sid-like channel transport. Comparatively, clathrin-mediated endocytosis appears to be the most conserved mechanism across insects, including the red flour beetle, Tribolium castaneum (Coleoptera), and the Asian corn borer, Ostrinia furnacalis (Lepidoptera).

Conclusions: Taken together, dsRNA enters the cells of different tissue types through diverse pathways. This systematic and comprehensive study not only advances our understanding of the cellular uptake of extracellular dsRNA and the resultant differential sensitivity to RNAi in insects, but also facilitates the ongoing integration of this species-specific biotechnology into sustainable integrated pest management practices.

Biomolecular condensates control key cellular processes, from gene expression to signal transduction, by organizing molecules through selective compartmentalization. Increasing evidence links their dysregulation to cancer, neurodegeneration, and other diseases, positioning condensates as promising therapeutic targets. This review explores emerging strategies that go beyond dissolving pathological condensates, including approaches that induce, redirect, or reprogram their dynamics, composition, and physical state. Rather than inhibiting individual proteins, these interventions reshape the cellular organization itself. By targeting the material and functional properties of condensates, such strategies offer a new conceptual framework for therapeutic design in complex, dysregulated biological systems.

Background: Hosts can use avoidance (e.g., behavior) to reduce their contact rates with pathogens; after contact, they can use resistance (e.g., immunity) to reduce the establishment and proliferation of an infection. Because both defenses preserve host fitness and reduce pathogen fitness, we expect that their epidemiological and evolutionary effects will be interdependent. This study used a two-locus model to understand the evolution of allelic associations (i.e., linkage disequilibrium or LD) between genes determining levels of avoidance and resistance in the presence of an infectious disease or a parasite.

Results: We found that polymorphism in both avoidance and resistance was possible, but only for a limited range of parameter values. At equilibrium within these polymorphic populations, avoidance and resistance alleles were negatively associated (i.e., in negative LD). However, most commonly, polymorphism was only stably maintained at one defense locus, and the other locus became fixed for one allele.

Conclusions: The model shows that avoidance and resistance are likely to influence each other's evolution because of their joint effects on infection and their costs; however, predictions about their relationship are not necessarily straightforward or intuitive. For example, avoidance and resistance may be more likely to covary across than within populations.

Background: The Chengdu Plain and surrounding regions (CPS) host a diverse mosaic of archaeological cultures and ethnolinguistic groups, yet the origins of these populations and the extent of Western Eurasian and East Asian influences remain unclear and underrepresented in genomic studies. As a molecular archaeological archive, Y-chromosome data provide vital insights into the paternal genetic history of ancient Shu populations and their descendants.

Methods: Here, we combine our newly generated genomic data with publicly available large-scale whole-Y-chromosome sequences from East Asia to reconstruct the phylogeny and paternal history of both modern and ancient CPS populations. Our merged dataset includes 2737 whole-Y sequences and 312 ancient samples, revealing a complex regional paternal genetic history.

Results: We identify 970 Y-chromosome clades, covering both common East Asian indigenous haplogroups (O, C, D, N) and rare incoming haplogroups (Q, J, R, F, H), and observe distinct distribution patterns across ethnically diverse Han, Tibetan, Yi, Qiang, and Hui groups in CPS. Population modeling uncovers fine-scale substructures influenced by ethnolinguistic and geographic factors, emphasizing the dominant paternal contributions of indigenous East Asian millet- and rice-farming groups. Time-calibrated phylogenies indicate that the founding populations of the ancient Shu civilization primarily derived from East Asian millet- and rice-based agricultural communities, with limited gene flow from Western steppe pastoralists.

Conclusions: Our findings enhance the understanding of the paternal genetic landscape of CPS populations and shed light on key demographic transitions during the Neolithic and Bronze Age.

Background: Cercozoa are single-celled eukaryotes (protists) and are part of the supergroup Rhizaria. Cercozoans have vastly different morphologies and are defined by their phylogenetic affinity. While the group includes some well-known and well-researched taxa, like the chlorarachniophytes, we know very little about the remainder. Most of these are predatory protists found in soil and marine sediments, but they also include marine plankton and are underrepresented in multigene phylogenetic trees of Rhizaria, thus missing much of their diversity. We employed single-cell transcriptomics to broadly sample this uncultured diversity of Cercozoa.

Results: We generated a taxon-comprehensive multigene tree of Cercozoa that includes many previously unsampled groups, increasing taxon sampling by more than 300%. We report five novel and previously unknown lineages and two lineages that were known only from environmental sequences. Several previously established clades are recovered, like Thecofilosea, Phaeodaria, and Thaumatomonadida, but others, like the class Imbricatea, are not. We find both single and double amino-acid insertions between polyubiquitin monomers in all our assemblies, suggesting a complex pattern across Cercozoa.

Conclusions: A single-cell transcriptomics approach generated a wealth of molecular and morphological image data for phylogenomics. This phylogenetic framework is in turn the groundwork for additional analyses to further our understanding of the basic biology of Cercozoa and their diversity. This study also highlights the number of previously unsampled taxa and completely novel lineages in Rhizaria and Cercozoa in particular.

Background: Horizontal gene transfer (HGT) is a major driver of microbial evolution, yet the influence of host cellular context on the integration and functionality of transferred genes remains underexplored. In this study, we investigate how host background impacts the horizontal acquisition of post-translational modification (PTM) machinery. Here, we use heterologous expression of the highly conserved and frequently horizontally transferred translational elongation factor P (EF-P) from diverse species in Escherichia coli as a model. EF-P has a heterogenous relationship with PTMs; three characterized variants each undergo distinct PTM pathways, while others function effectively without any modification.

Results: We demonstrate that EF-P from Deinococcus radiodurans, Geoalkalibacter ferrihydriticus, and Nitrosomonas communis can complement an EF-P knockout in E. coli without requiring any PTM, suggesting they may represent new examples of unmodified EF-P. We also found that the EF-P from the Thermotogota Mesotoga prima is post-translationally modified in an off-target reaction by the rhamnosylation enzyme EarP, thus interfering with its functionality. Conversely, we saw that rhamnosylation by EarP does not impact the function of the EF-P-like protein EfpL.

Conclusions: Our findings highlight that PTM systems introduced via HGT can have varied effects on host proteins. We found that different EF-P variants are impacted in different ways by off-target rhamnosylation. While some of these off-target reactions may present opportunities to develop novel, catalytically active PTMs, others are detrimental to the function of the modified EF-P. Our results emphasize the complexity of gene integration and functional compatibility in foreign genomic contexts.

Background: Trypanosomatids are parasitic flagellates best known for human pathogens causing sleeping sickness, Chagas disease, and leishmaniasis. RNA viruses infecting these protists have recently gained attention for their role in disease severity. While numerous such viruses have been described in Leishmania and several other trypanosomatid genera, none has previously been documented in the iconic genus Trypanosoma.

Results: We report the first discovery and molecular characterization of RNA viruses in trypanosomes, identifying a leishmaniavirus and two narnaviruses in a single strain of Trypanosoma platydactyli, a parasite of the common wall gecko. The leishmaniavirus genome revealed a conserved organization, including a putative ribosomal frameshift site and a hairpin-like secondary structure typical of the genus. Phylogenetic inference indicates that it is closely related to leishmaniaviruses from Old World Leishmania spp., consistent with shared vector ecology. The two narnaviruses have distinct origins, although both cluster with viruses of other trypanosomatids, suggesting historical exchanges among co-infecting parasites.

Conclusions: Our study expands both the known diversity of RNA viruses in trypanosomatids and the range of trypanosomatid genera that host these viruses, providing guidance for future screening. We suggest that vector ecology-particularly feeding behavior-may influence viral acquisition by trypanosomes, explaining the previous absence of viral reports from intensively studied trypanosomes of medical relevance vectored by tsetse flies or kissing bugs. Therefore, overlooked species transmitted by Nematocera represent promising candidates for future viral discovery. This concept extends beyond trypanosomatids, providing a general framework for understanding the conditions that permit viral host switching by viruses among microeukaryotes.

Background: Leontynka is a non-photosynthetic lineage of the order Chlamydomonadales (Chlorophyta). Although many Chlamydomonadales members encode components of the anaerobic energy metabolism, studies focused on Chlamydomonadales algae thriving in hypoxia and not prospering in oxic conditions are missing. Using a combination of experimental approaches, comparative genomics, and advanced in silico protein localization analyses, we employed Leontynka as a model to investigate the evolution of anaerobiosis in Chlamydomonadales.

Results: Leontynka spp. accumulate a wide range of storage forms, enabling them to cope with nutritional stresses. Their mitochondria contain well-developed cristae mediating a conventional aerobic energy metabolism. Moreover, colocalization of a Raman signal for cytochromes with the position of mitochondria in the cell indicates that oxidative phosphorylation is an important route of energy metabolism in the alga. Interestingly, Leontynka spp. concentrate enzymes potentially involved in oxygen-independent ATP synthesis within the plastid, which lost the ability to produce ATP using proton gradient generated by membrane complexes that exploit redox reactions. We analyzed the composition of prokaryotic communities co-isolated with Leontynka spp. and hypothesize that their preference for hypoxic/microoxic conditions is facilitated by metabolic interactions with certain microaerophilic and anaerobic bacteria.

Conclusions: This study represents the first comprehensive analysis of microaerophilic Chlamydomonadales algae. Having retained several ancestral enzymes of the anaerobic energy metabolism, Leontynka represents a unique vantage point for understanding the evolution of the hydrogen production machinery and adaptations to low oxygen in Chlamydomonadales (and core chlorophytes in general). Our findings suggest that the plastid of non-photosynthetic Leontynka follows a similar evolutionary path as mitochondria when adapting to anaerobiosis and parallels the transition of a mitochondrion into a hydrogenosome.

Background: Given the ecological importance of reef-building corals (Scleractinia), it is perhaps surprising that the molecular mechanisms underlying many of the morphological and metabolic changes during their development remain unclear. In part, this is due to the lack of a comprehensive transcriptomic dataset for any coral. A second challenge in the analysis of such non-model developmental datasets is that the volume of data often complicates its interpretation.

Results: To overcome these limitations, we profiled gene expression in Acropora millepora across 26 life stages from unfertilised eggs to juvenile polyps and developed an interactive online tool based on the R-application Shiny to simultaneously visualise changes in the expression of large numbers of genes. As expected, major transcriptomic changes (transitions) occurred during gastrulation and the acquisition of competence. Surprisingly, however, settlement triggered by using an extract of the natural inducing crustose coralline alga did not immediately lead to major changes in gene expression, but a major transition involving many genes was observed 3-6 h after settlement induction.

Conclusions: We hope that providing access to this extensive developmental transcriptome dataset and software to facilitate its analysis will expedite a better understanding of the changes that occur during coral development. The online tool is available at https://amil-deview.mmb.group.

Background: Cycle of glacial contraction and postglacial expansion in widespread European organisms, as inferred from neutral genetic markers, has led to classic phylogeographic divergence and a primarily latitudinal gradient in genetic diversity. However, the relative contribution of adaptive loci, compared to neutral loci, in shaping complex phylogeographic patterns remains poorly understood.

Results: We generated extensive genomic datasets for the widespread European species Aquarius najas and its relatives (Aquarius cinereus and Aquarius ventralis), sampled across their entire European distribution. Our results revealed that A. najas is divided into northern and southern lineages, driven in part by major biogeographical barriers in Europe through neutral processes. Additionally, we discovered northern populations exhibiting unexpectedly high genetic diversity, consistent with the cryptic extra-Mediterranean refugia hypothesis. These populations showed evidence of strong, rapid local adaptation, as indicated by the identification of 52 temperature-associated genes (e.g., regulating MAPK thermosensitivity). For the Ibero-Maghrebian populations, our analyses uncovered significant mitochondrial and nuclear introgression from A. cinereus into A. najas. Notably, we identified adaptive introgressed genes, including an ATP-binding cassette (ABC) transporter and the zinc finger protein ZFP91, which likely enhance survival and fitness in the Maghreb region.

Conclusions: Our study presents a comprehensive paradigm for understanding how widespread, limited-dispersal European species adapt to heterogeneous environments through the combined effects of rapid local selection and adaptive introgression, extending beyond the influence of neutral processes alone. Furthermore, we designed and implemented an extended framework for phylogeographic investigation that incorporates both neutral and adaptive dimensions.