Biology subjects

Rodriguez, F.

Publications and source records attributed to Rodriguez, F..

At least 19 recordsLinked to original sources

bioRxiv2026

A distributed pallial circuit links sensory and bodily representations to aversive motivational value in the goldfish dorsomedial pallium

Understanding how neural circuits transform sensory and bodily signals into motivational states and adaptive behavior is a central problem in neuroscience. In teleost fish, the dorsomedial telencephalon (Dm) is a key pallial region implicated in both sensory processing and aversive behavior, yet whether these functions arise from a functionally uniform region or from interactions among specialized pallial domains has remained unknown. Here we show that the teleost dorsomedial telencephalon exhibits a previously unrecognized functional organization in which distinct but interconnected pallial domains perform complementary computations that progressively transform multimodal sensory and bodily representations into aversive motivational value and adaptive behavioral control. Wide-field voltage-sensitive dye imaging revealed that tactile, auditory, and gustatory stimuli evoke spatially organized, modality-specific activity exclusively within the caudal subdivision of Dm (Dmc), whereas the rostral subdivision (Dmr) showed little or no sensory responsiveness. In contrast, focal intracerebral microstimulation demonstrated that activation of Dmr, but not Dmc, is sufficient to generate robust, flexible, and reversible conditioned place avoidance, identifying Dmr as a pallial node causally involved in the assignment of negative motivational value. Anatomical tracing revealed a circuit in which sensory and bodily-related inputs converge onto Dmc, are relayed intrapallially to Dmr, where they are transformed into an aversive motivational signal before being conveyed to hypothalamic and brainstem centers involved in autonomic and behavioral regulation. Immunohistochemical analyses confirmed the pallial identity of both subdivisions and their distinct rostrocaudal organization, while providing no evidence that Dm corresponds to a classical pallial amygdaloid territory. This functional architecture more closely resembles the distributed organization of mammalian corticolimbic networks than either a unitary pallial amygdala or a neocortical sensory hierarchy, suggesting that the transformation of sensory and bodily representations into motivational control may represent a conserved organizational feature of the pallium that emerged early during vertebrate evolution. Short abstract / Significance statementThis study shows that the teleost dorsomedial pallium is organized into complementary functional domains that dissociate multimodal sensory representation from negative motivational processing while forming an interconnected pallial circuit associated with adaptive behavioral control. Our findings reveal a distributed pallial organization resembling mammalian corticolimbic architectures and provide a new framework for understanding the evolution of vertebrate pallial function.

neuroscience↗

bioRxiv2026

T-cell Receptor (TCR) targeting with Multivalent T-cell Engagers

T-cell engagers (TCEs) for cancer immunotherapy have traditionally relied on high affinity single chain fragment variable (scFv) domains to target CD3, specifically the {varepsilon} chain, for the activation of T-cells. Despite their clinical success, there have been reports of TCEs driving systemic toxicity, non-specific T-cell activation, on-target off-tumor effects, and severe inflammation due to cytokine release. To address these limitations, we designed multivalent TCEs using Chemically Self-Assembled Nanorings (CSANs) that target the /{beta} constant region of the T-cell receptor (TCR) in the TCR/CD3 complex using a moderate affinity TCR nanobody (TCRVHH). Nanobodies offer superior physical and chemical properties over scFvs-including higher solubility, stability and lower production cost-making them increasingly popular as structural units of TCEs. We compared the efficacy and safety profile of this moderate affinity, nanobody-based TCR binder against high affinity CD3scFv based CSANs across EGFR and PSMA expressing solid tumor models. While the CD3scFv CSANs offered potent cytotoxicity, they also induced antigen independent T-cell activation bypassing the requirement of tumor crosslinking for cytotoxicity. In contrast the TCRVHH CSANs required strict antigen engagement to trigger cytotoxicity, significantly reducing non-specific T-cell activation and thus enhancing the safety profile. Although the initiation of cytotoxicity was kinetically slower than the CD3scFv counterpart, TCRVHH CSANs achieved comparable end point cytotoxicity across multiple antigen densities, as well as in 3D tumor spheroids. Through this study we demonstrate the applicability of nanobodies as T-cell targeting domains, enhanced specificity and safety of moderate affinity T-cells binders and the diversification of T-cell targeting epitopes without compromising the efficacy of TCEs. Abstract Graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=96 SRC="FIGDIR/small/725710v2_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@9bcb83org.highwire.dtl.DTLVardef@4e30daorg.highwire.dtl.DTLVardef@1695931org.highwire.dtl.DTLVardef@15ec7ab_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

The aging modulator miR-29 is essential for adult cardiomyocyte function

Aging is the main risk factor for cardiovascular diseases, underscoring the need to identify the molecular regulators that sustain cardiac function during aging. The microRNA miR-29 is a well-established aging-associated regulator as its expression increases with age, and its overexpression promotes premature aging. Here, we define the cardiomyocyte-autonomous role of miR-29 in the adult heart by generating an inducible, cardiomyocyte-specific miR-29-deficient mouse model (Heart-iKO). We show that Heart-iKO mice develop dilated cardiomyopathy (DCM) with reduced ejection fraction that ultimately leads to premature death. Mechanistically, Heart-iKO cardiomyocytes exhibit alterations in mitochondrial structure and function. Transcriptomic profiling of bulk heart tissue and isolated cardiomyocytes revealed a consistent downregulation of genes involved in oxidative phosphorylation and the electron transport chain. We further observed a similar pattern of mitochondrial impairment in miR-29-deficient human cardiomyocytes derived from induced pluripotent stem cells (CM-iPSCs). Together, these findings highlight the context-dependent role of miR-29 in cardiac physiology and aging: although its upregulation promotes premature aging, its basal expression is required to maintain mitochondrial homeostasis and prevent heart failure in the adult myocardium.

physiology↗

bioRxiv2026

SENSORY MAPS IN THE TELENCEPHALIC PALLIUM OF GOLDFISH.

The functional organization of the teleost telencephalic pallium remains poorly understood, particularly regarding the presence of modality-specific sensory domains and their topographic arrangement. Here, we used in vivo wide-field voltage-sensitive dye imaging to map sensory-evoked neural activity across the dorsal surface of the telencephalic pallium of adult goldfish. Somatosensory, auditory, gustatory, and visual stimulation revealed distinct, modality-specific domains primarily located within the dorsomedial (Dm) and dorsolateral (Dl) pallium. Within Dm, somatosensory and auditory stimuli activated partially overlapping territories in the caudal subregion (Dm4), exhibiting clear somatotopic and tonotopic organization along the mediolateral axis. Gustatory stimulation selectively engaged Dm3, where different tastants activated spatially distinct but partially overlapping domains. A more rostral subregion (Dm2) responded only to high-intensity somatosensory stimulation, suggesting involvement in processing negatively valenced inputs. Visual stimulation activated a circumscribed area within the dorsolateral pallium (Dld2),that closely matched cytoarchitectural boundaries. Pharmacological blockade of ionotropic glutamate receptors markedly reduced sensory-evoked responses, indicating that these maps depend on glutamatergic synaptic transmission. Together, these findings show that the goldfish pallium contains distinct, spatially organized sensory representations and a refined internal functional architecture. This organization suggests that pallial topographic sensory maps may not be exclusive to mammals and birds. Based on these results, we propose that dorsomedial and dorsolateral pallial regions may be functionally comparable to components of the mammalian mesocortical network, more than to the pallial amygdala or the neocortex. This framework provides a new perspective on pallial organization in teleosts and contributes to understanding the evolutionary origins of the vertebrate pallium. HIGHLIGHTSO_LIVoltage-sensitive dye imaging was used to map sensory responses in the goldfish pallium. C_LIO_LIDistinct sensory areas for somatosensory, auditory, gustatory, and visual modalities were identified. C_LIO_LISome sensory regions in Dm show topographically organized maps. C_LIO_LIFunctional segregation suggests a complex, non-diffuse pallial organization. C_LIO_LIFindings support a novel hypothesis linking Dm and Dld to mammalian mesocortical regions. C_LI

neuroscience↗

bioRxiv2026

Understanding heterogeneous responses to T cell engagers: Binding characteristics and dosing thresholds determine cytotoxic efficacy

Therapeutic efficacy of multivalent T cell engagers varies widely across individuals, but the basis for this heterogeneity remains poorly understood. Here, we integrate in vitro experiments of antitumor immune responses with a mechanistic modeling framework to investigate sources of response variability across T cell donors and TE constructs, focusing on a novel multivalent bispecific T cell engager currently in development. We identify parameter regimes that accurately recapitulate dose-response behaviors across T cell donors and doses, and perform cross-validation studies that demonstrate the models predictive accuracy. We find that variability in therapy efficacy is governed by the relationship between binding affinity and dose. When dose exceeds the binding affinity, responses are relatively robust across donors; when dose is below the binding affinity, responses are more donor dependent. At smaller doses, the TE-specific shape characteristics of the tumor-binding dose response, its steepness in particular, is a key marker of therapy efficacy. More generally, our integrated modeling and experimental framework offers insights and tools that are applicable to other bispecific T-cell engagers, and provides a quantitative foundation for the systematic, in silico optimization of TE design and dosing strategies.

immunology↗

bioRxiv2025

Distinct cytotoxic cell subsets underlie protective and non-protective immunity to African swine fever virus

Limited understanding of African swine fever (ASF) immunity remains a major barrier to the rational development of safe and effective vaccines. While antibody-mediated protection is still poorly defined, growing evidence highlights a central role for cellular immunity. In particular, cytotoxic cells have emerged as key components to control ASF virus (ASFV) infection. However, the contribution of individual cytotoxic subsets across different virological and immunological contexts is not well characterised. Here, we investigated cytotoxic responses during BA71{Delta}CD2 live attenuated vaccine (LAV)-induced protection and during late-stage lethal ASFV infection, and demonstrated the involvement of different cytotoxic subsets in each scenario. Early increases in perforin-producing CD8{beta}+ T cells in blood after immunisation coincided with the onset of protection. At later time points, elevated levels of these cells after in vitro ASFV-specific stimulation correlated with survival to lethal challenge, supporting their central role in protective immunity. Additional correlates of protection during recall responses included CD4+CD8{beta}+ cytotoxic T cells, IFN{gamma}-producing cells, and ASFV-specific antibodies, illustrating the multifactorial nature of immunity to ASF. In contrast, pigs with acute ASF exhibited a distinct cytotoxic profile characterised by broad increases across multiple perforin-producing subsets. Although all of them showed reduced susceptibility to ASFV-induced lymphopenia, only perforin-producing NK and{gamma}{delta} T cells correlated with viremia, suggesting their active involvement during late disease. Together, these findings advance our understanding of cytotoxic responses to ASFV and identify cytotoxic T cells, alongside other immune components, as potential correlates of protection that may guide future vaccine development.

immunology↗

bioRxiv2025

Multivalent Tri-Functional T-cell Engagers by Chemically Induced Protein Self-Assembly

T-cell engagers (TCEs) show promise in cancer immunotherapy but face challenges in solid tumors due to heterogeneity, antigen escape, and limited T-cell infiltration. To address this, we developed a modular platform using chemically self-assembled nanorings (CSANs). We engineered a bifunctional fusion protein, E1-DHFR2-CD3, with an EGFR-binding fibronectin (E1) and an anti-CD3 scFv on a DHFR2 scaffold. With bis-methotrexate, the monomers formed multivalent cis-CSANs. Both monomers and CSANs bound EGFR+ tumor cells and T-cells, were internalized, and induced dose-dependent, EGFR- and T-cell-dependent cytotoxicity in co-culture assays. The system was reproducible across T-cell donors. To expand targeting, E1-DHFR2-CD3 co-assembled with other DHFR2 monomers targeting GFP or EpCAM, forming trispecific CSANs capable of binding multiple antigens and mediating cytotoxicity. This platform enables the discovery of potent multispecific TCEs to address antigen escape and solid tumor heterogeneity. Future work will focus on optimizing antigen combinations to enhance efficacy across breast cancer subtypes.

immunology↗

bioRxiv2025

The early human interferon gamma response to Toxoplasma gondii is driven by Vγ9Vδ2 T-cell sensing of host phosphoantigens and subsequent NK-cell activation

Toxoplasma gondii is a globally prevalent intracellular parasite that infects [~]40 million Americans. The murine immune response to Toxoplasma relies on both toll-like receptor (TLR) 11/12 and immunity related GTPase-mediated (IRGs) responses, which humans lack, making it unclear how the human immune response detects and responds to the parasite. We investigated whether human V{gamma}9V{delta}2 T cells, which detect phosphoantigens through the BTN3A1 receptor, shape the early immune response to the parasite. Using primary human peripheral blood mononuclear cells (PBMCs), we show that V{gamma}9V{delta}2 T cells are activated by Toxoplasma-infected cells in a BTN3A1- dependent manner leading to secretion of interferon gamma (IFN{gamma}) and tumor necrosis factor-alpha (TNF). Additionally, these T cells potentiate IFN{gamma} production by natural killer (NK) cells, likely via TNF and interleukin (IL)-12 produced during infection. Active parasite invasion is required to stimulate the IFN{gamma} response, and inhibition of the host mevalonate pathway, which limits the synthesis of the phosphoantigen isopentenyl pyrophosphate (IPP), attenuates the cytokine response, indicating Toxoplasma infection increases host phosphoantigens leading to V{gamma}9V{delta}2 T cell activation. Our findings identify V{gamma}9V{delta}2 T cells as key effectors that potentiate NK cells in the early human immune response to Toxoplasma, bridging innate and adaptive immunity in the absence of TLR11/12 signaling.

immunology↗

bioRxiv2025

Retroelement expansions underlie genome evolution in stingless bees

Stingless bees are essential pollinators and emerging models for studying behavioral and genomic evolution. In the genus Melipona, a major difference in heterochromatin organization defines two groups: Group I species (e.g., M. quadrifasciata) with <50% of pericentromeric heterochromatin and Group II species (e.g., M. scutellaris) containing >50% heterochromatin across their chromosomes. These differences are thought to correlate with genome size and transposable element (TE) content, offering a unique opportunity to explore how heterochromatin variation, TE dynamics, and chromosomal evolution interact in a phylogenetic context. We present pseudo-chromosome-level genome assemblies for M. quadrifasciata and M. scutellaris obtained by long-read sequencing and Hi-C scaffolding. Comparative analyses reveal conserved synteny but marked divergence in structural variants and TEs. M. scutellaris shows an expansion of retrotransposons, particularly Gypsy/DIRS1 elements, concentrated in TE hotspots linked to chromosomal rearrangements and structural variants. This coincides with distinct methylation entropy and an expansion of histone deacetylase orthologs, potentially affecting heterochromatin organization. The increased ratio of retrotransposons in M. scutellaris is counterbalanced by more DNA transposons in M. quadrifasciata, resulting in genomes of similar overall sizes but of distinct heterochromatin distribution. Advancing our understanding of genome evolution in eusocial insects, we provide high-resolution genomic resources for two Melipona species that differ in heterochromatin content. Our results highlight the complex role of TEs in shaping genomes and underscore their influence on chromosomal and epigenetic innovation, providing strong evidence that TE dynamics underly the striking heterochromatic differences observed in Melipona.

genomics↗

bioRxiv2024

Autophagy controls differentiation of Drosophila blood cells by regulating Notch levels in response to nutrient availability

Drosophila larval hematopoiesis takes place at the lymph gland, where blood cell progenitors differentiate into two possible cell types: plasmatocytes, analogous to mammalian macrophages, or crystal cells that share features with mammalian megakaryocytes; a third cell type, the lamellocytes, can develop only upon specific immune challenges. In this work, we investigate the role of autophagy in Drosophila hematopoiesis. We found that autophagy inhibition in blood cell progenitors results in augmented crystal cell differentiation due to accumulation of high levels of Notch protein. Notch activation during hematopoiesis depends on the endocytic pathway, which cross-talks with autophagy: While endocytosis and endosomal maturation are essential for Notch activation, autophagosomes are required for Notch lysosomal degradation. TOR signaling inhibits autophagosome biogenesis, which in turn prevents the formation of Notch-containing amphisomes, being the latter necessary for Notch lysosomal destruction. Reduction of Notch lysosomal degradation shifts the balance towards Notch activation at late endosomal membranes, thereby enhancing differentiation of crystal cells. Our work defines a novel mechanism of regulation of immune cell differentiation in response to the nutritional status of the organism: High nutrient availability induces TOR activation, thereby inhibiting autophagy, hindering lysosomal degradation of Notch, and promoting crystal cell differentiation.

developmental biology↗

bioRxiv2024

Pore formation at the lytic synapse triggers the canonical pyroptotic cell death pathway

Prokaryotic pore-forming toxins drive inflammasome activation and pyroptosis through K+-dependent activation of the canonical NLRP3/caspase-1/gasdermin D signaling axis. In this study, we hypothesized that perforin, a eukaryotic pore-forming protein released into the lytic synapse by antigen-specific cytotoxic T lymphocytes (CTLs) upon cognate antigen recognition, mimics the pro-pyroptotic activity of ancestral pore-forming toxins, complementing its role as a conduit for granzymes. Utilizing imaging and molecular approaches, we demonstrate that perforation of target cells upon CTL attack elicits swift K+ efflux followed by NLRP3-dependent activation of proinflammatory caspase-1 and its major substrate, the pyroptotic executioner gasdermin D (GSDMD). Acute target cell death upon CTL attack is gasdermin-dependent and demonstrates morphological and molecular features of pyroptosis, including pyroptotic body formation, cell bloating, plasma membrane rupture, and release of intracellular contents. Perforation of target cells by soluble perforin is sufficient to trigger rapid K+ efflux, caspase-1 activation, and pyroptosis. By contrast, sustained interaction with CTLs unmasks a delayed apoptotic phenotype in the remaining target cells. Interestingly, exposure of target cells to exogenous supramolecular attack particles (SMAPs) recapitulates this apoptotic phenotype, suggesting that soluble perforin and SMAPs play dichotomous roles in target cell death. Our results reveal a novel mechanism for engagement of pyroptotic machinery upon CTL attack, in which perforin itself can autonomously engage programmed cell death (PCD), highlighting the complexity and diversity of the CTL lytic arsenal.

immunology↗

bioRxiv2023

The response to ketogenic diet in colorectal cancer is mediated by lasting functional alterations of the gut microbiome

Colorectal cancer (CRC) patients have been shown to possess an altered gut microbiome. Diet is a well-established modulator of the microbiome, and thus, dietary interventions might have a beneficial effect on CRC. An attenuating effect of the ketogenic diet (KD) on CRC cell growth has been previously observed, however the role of the gut microbiome in driving this effect remains unknown. Here, we describe a reduced colonic tumor burden upon KD consumption in a CRC mouse model with a humanized microbiome. Importantly, we demonstrate a causal relationship through microbiome transplantation into germ-free mice, whereby alterations in the gut microbiota were maintained in the absence of continued selective pressure from the KD. Specifically, we identify a shift toward bacterial species that produce stearic acid in ketogenic conditions, whereas consumers were depleted, resulting in elevated levels of free stearate in the gut lumen. This microbial product demonstrated tumor-suppressing properties by inducing apoptosis in cancer cells and decreasing colonic Th17 immune cell populations. Taken together, the beneficial effects of the KD are mediated through alterations in the gut microbiome, including, among others, increased stearic acid production, which in turn significantly reduces intestinal tumor growth.

cancer biology↗

bioRxiv2023

Distinct Myeloid Derived Suppressor Cell Populations Promote Tumor Aggression in Glioblastoma

The diversity of genetic programs and cellular plasticity of glioma-associated myeloid cells, and thus their contribution to tumor growth and immune evasion, is poorly understood. We performed single cell RNA-sequencing of immune and tumor cells from 33 glioma patients of varying tumor grades. We identified two populations characteristic of myeloid derived suppressor cells (MDSC), unique to glioblastoma (GBM) and absent in grades II and III tumors: i) an early progenitor population (E-MDSC) characterized by strong upregulation of multiple catabolic, anabolic, oxidative stress, and hypoxia pathways typically observed within tumor cells themselves, and ii) a monocytic MDSC (M-MDSC) population. The E-MDSCs geographically co-localize with a subset of highly metabolic glioma stem-like tumor cells with a mesenchymal program in the pseudopalisading region, a pathognomonic feature of GBMs associated with poor prognosis. Ligand-receptor interaction analysis revealed symbiotic cross-talk between the stemlike tumor cells and E-MDSCs in GBM, whereby glioma stem cells produce chemokines attracting E-MDSCs, which in turn produce growth and survival factors for the tumor cells. Our large-scale single-cell analysis elucidated unique MDSC populations as key facilitators of GBM progression and mediators of tumor immunosuppression, suggesting that targeting these specific myeloid compartments, including their metabolic programs, may be a promising therapeutic intervention in this deadly cancer. One-Sentence SummaryAggressive glioblastoma harbors two unique myeloid populations capable of promoting stem-like properties of tumor cells and suppressing T cell function in the tumor microenvironment.

immunology↗

bioRxiv2022

Chromosome-level genome assembly and annotation of two lineages of the ant Cataglyphis hispanica: steppingstones towards genomic studies of hybridogenesis and thermal adaptation in desert ants

AO_SCPLOWBSTRACTC_SCPLOWCataglyphis are thermophilic ants that forage during the day when temperatures are highest and sometimes close to their critical thermal limit. Several Cataglyphis species have evolved unusual reproductive systems such as facultative queen parthenogenesis or social hybridogenesis, which have not yet been investigated in detail at the molecular level. We generated high-quality genome assemblies for two hybridogenetic lineages of the Iberian ant Cataglyphis hispanica using long-read Nanopore sequencing and exploited chromosome conformation capture (3C) sequencing to assemble contigs into 26 and 27 chromosomes, respectively. Further karyotype analyses confirm this difference in chromosome numbers between lineages; however, they also suggest it may not be fixed among lineages. We obtained transcriptomic data to assist gene annotation and built custom repeat libraries for each of the two assemblies. Comparative analyses with 19 other published ant genomes were also conducted. These new genomic resources pave the way for exploring the genetic mechanisms underlying the remarkable thermal adaptation and the molecular mechanisms associated with transitions between different genetic systems characteristic of the ant genus Cataglyphis.

genomics↗

bioRxiv2021

An ancient clade of Penelope-like retroelements with permuted domains is present in the green lineage and protists, and dominates many invertebrate genomes

Penelope-like elements (PLEs) are an enigmatic clade of retroelements whose reverse transcriptases (RTs) share a most recent common ancestor with telomerase RTs. The single ORF of canonical EN+ PLEs encodes RT and a C-terminal GIY-YIG endonuclease (EN) that enables intrachromosomal integration, while EN-PLEs lack endonuclease and are generally restricted to chromosome termini. EN+ PLEs have only been found in animals, except for one case of horizontal transfer to conifers, while EN-PLEs occur in several kingdoms. Here we report a new, deep-branching PLE clade with a permuted domain order, whereby an N-terminal GIY-YIG endonuclease is linked to a C-terminal RT by a short domain with a characteristic Zn-finger-like motif. These N-terminal EN+ PLEs share a structural organization, including pseudo-LTRs and complex tandem/inverted insertions, with canonical EN+ PLEs from Penelope/Poseidon, Neptune and Nematis clades, and show insertion bias for microsatellites, but lack hammerhead ribozyme motifs. However, their phylogenetic distribution is much broader. The Naiad clade is found in numerous invertebrate phyla, where they can reach tens of thousands of copies per genome. Naiads in spiders and clams independently evolved to encode selenoproteins. Chlamys, which lack the CCHH motif universal to PLE endonucleases, occur in green algae, spike mosses (targeting ribosomal DNA) and the slime mold Physarum. Unlike canonical PLEs, RTs of N-terminal EN+ PLEs contain the insertion-in-fingers domain, strengthening the link between PLEs and telomerases. Additionally, we describe Hydra, a novel metazoan C-terminal EN+ clade. Overall, we conclude that PLE diversity, distribution and abundance is comparable to non-LTR and LTR-retrotransposons.

molecular biology↗

bioRxiv2020

Evolutionary dynamics of transposable elements in bdelloid rotifers

Transposable elements (TEs) are selfish genomic parasites whose ability to spread autonomously is facilitated by sexual reproduction in their hosts. If hosts become obligately asexual, TE frequencies and dynamics are predicted to change dramatically, but the long-term outcome is unclear. Here, we test current theory using whole-genome sequence data from eight species of bdelloid rotifers, a class of invertebrates where males are thus far unknown. Contrary to expectations, we find a diverse range of active TEs in bdelloid genomes, at an overall frequency within the range seen in sexual species. We find no evidence that TEs are spread by cryptic recombination or restrained by unusual DNA repair mechanisms, but we report that bdelloids share a large and unusual expansion of genes involved in RNAi-mediated TE suppression. This suggests that enhanced cellular defence mechanisms might mitigate the deleterious effects of active TEs and compensate for the consequences of long-term asexuality.

evolutionary biology↗

bioRxiv2020

The Genetic Variation Landscape of African Swine Fever Virus Reveals Frequent Positive Selection on Amino Acid Replacements

African swine fever virus (ASFV) is a lethal disease agent that causes high mortality in swine population and devastating loss in swine industries. The development of efficacious vaccines has been hindered by the gap in knowledge concerning genetic variation of ASFV and the genetic factors involved in host adaptation and virus-host interactions. In this study, we performed a meta-genetic study of ASFV aiming to profile the variation landscape and identify genetic factors with signatures of positive selection and relevance to host adaptation. Our data reveals a high level of genetic variability of ASFV shaped by both diversifying selection and selective sweep. The selection signatures are widely distributed across the genome with the diversifying selection falling within 29 genes and selection sweep within 25 genes, highlighting strong signals of adaptive evolution of ASFV. Further examination of the sequence properties reveals the link of the selection signatures with virus-host interactions and adaptive flexibility. Specifically, we discovered a site at 157th of the key antigen protein EP402R under diversifying selection, which is located in the cytotoxic T-cell epitope related with the low level of cross-reaction in T-cell response. Importantly, two multigene families MGF360 and MGF505, the host range factors of ASFV, exhibit divergent selection among the paralogous members, conferring sequence pools for genetic diversification and adaptive capability. By integrating the genes with selection signatures into a unified framework of interactions between ASFV and hosts, we showed that the genes are involved in multiple processes of host immune interaction and virus life cycles, and may play crucial roles in circumventing host defense systems and enhancing adaptive fitness. Our findings will allow enhanced understanding of genetic basis of rapid spreading and adaptation of ASFV among the hosts.

evolutionary biology↗

bioRxiv2020

A paleogenetic perspective of the Sabana de Bogota (Northern South America) population history over the Holocene (9000 - 550 cal BP)

ABSTRACTOn the basis of distinct lines of evidence, detailed reconstructions of the Holocene population history of the Sabana de Bogota (SB) region, Northern South America, have been performed. Currently, there exist two competing models that support temporal continuity or, alternatively, divergence. Despite recent research that lends support to the population discontinuity model, several discrepancies remain, calling for other kinds of evidences to be explored for a more detailed picture of Holocene biocultural evolution. In this study, we analyze the mitochondrial genetic diversity of 30 individuals (including 15 newly reported complete mitochondrial genomes) recovered from several archaeological sites spanning from the late Pleistocene (12,164 cal BP) until the final late Holocene (2,751 cal BP) along with published data from the region dating [~]9,000-550 cal BP in order to investigate diachronic genetic change. Genetic diversity and distance indices were calculated, and demographic models tested in an approximate Bayesian computation (ABC) framework to evaluate whether patterns of genetic affinities of the SB prehispanic populations support genetic continuity or discontinuity. The results show that mitochondrial genomes of the complete dataset fall within the Native American haplogroups A2, B2, C1b, D1 and D4h3a. Haplotype and nucleotide diversity declined over time with further evidence of genetic drift and remarkable reduction of genetic diversity during the final late Holocene. Inter-population distances and the exact test of population differentiation, as well as demographic simulations show no population differentiation and population continuity over time. Consequently, based on the analyzed data, we cannot reject the genetic continuity in the SB region as a plausible population history scenario. However, the restriction of the analyses to the Hyper Variable Region 1 of the mitochondrial genome, and the very low sample size both constitute significant limitations to infer evolutionary history.

genetics↗