Biology subjects

Prakash, A.

Publications and source records attributed to Prakash, A..

At least 19 recordsLinked to original sources

bioRxiv2026

Strain handling exposes IS-mediated recurrent genome reduction at a dynamic accessory locus in Komagataeibacter rhaeticus

Bacterial genomes are dynamic and harbour accessory regions that can be gained, lost, or rearranged in response to selective pressures. Members of the genus Komagataeibacter are used for bacterial cellulose production and researched as platforms for engineered living materials. However, their genomes are rich in mobile genetic elements (MGEs), including insertion sequences (ISs), genomic islands and prophage remnants, which drive genome rearrangements under agitated cultivation conditions. Whether this genome architecture contributes to genomic changes during routine strain maintenance and distribution remains poorly understood. Comparative genome sequencing of independent Komagataeibacter rhaeticus iGEM stocks revealed recurrent loss of a 210 kbp chromosomal region flanked by homologous IS5 sequences. This deletion was identified in a stock received as an agar stab and reproduced from an intact-genome population subjected to simulated agar-stab handling. Phylogenomic analysis of the affected locus revealed gene-tree/species-tree discordance, heterogeneous GC content and multiple ISs, supporting its characterization as a dynamic accessory region. Populations carrying the larger genome reduction showed improved growth and cellulose production relative to the intact genome reference, whereas populations carrying a smaller nested deletion showed reduced performance. These findings demonstrate that routine strain handling is not necessarily genomically neutral and can expose structural genomic variabilities that generate population-level genomic heterogeneity with phenotypic consequences. For bacteria with MGE-rich genomes, handling history may represent an underappreciated source of genomic and phenotypic variation between laboratories. More broadly, identifying unstable accessory regions may highlight genomic content that is dispensable under laboratory conditions, providing candidates for genome streamlining and strain improvement.

microbiology↗

bioRxiv2026

Extracellular matrix properties and dynamics are important for butterfly scale nanostructure development

Butterfly wing scales are intricately structured, cuticle-derived, extensions of single scale cells. Their highly ordered structures confer a range of functions, including producing structural color, which depends upon unknown molecular mechanisms controlling the secretion and ordering of an extracellular matrix (ECM). To find the genes required for patterning the ECM we compare scale nanostructure development between structurally colored blue scales and non-iridescent black scales on the forewings of the butterfly Heliconius sara using transmission electron microscopy, RNA-seq and proteomics. We first determined that structural differences between the two scale types are established from about half-way through pupal development and then investigated differences in relevant genes and proteins between scale types from this stage onwards. We show that knockouts of the genes coding for zona pellucida (ZP) domain proteins, miniature and trinity, and the cuticle protein gene, Cpr128 produce distinct effects on scale morphology and structure formation. In particular, some highly unusual scale morphologies are observed in miniature knockout individuals, suggesting a previously undescribed role of ZP domain proteins in structuring the ECM of scale cells and in mediating the mechanochemical interactions needed to produce the complex extracellular structures important for biological function in this system.

developmental biology↗

bioRxiv2026

PPM1B utilizes a trinuclear metal architecture for phosphatase activity

The metal-dependent protein phosphatase (PPM/PP2C) family regulates innate immune and cell death pathways through reversible phosphorylation. Although these enzymes contain a conserved third Mg2+/Mn2+ ion (M3) that is essential for activity, its chemical role in phosphate hydrolysis has remained unclear. Here, we report studies that reveal PPM1B promotes cell death during Pseudomonas aeruginosa infection and utilizes a trinuclear metal center in which M3 directly coordinates the substrate phosphate, positioning it for in-line SN2 hydrolysis. In addition to substrate orientation, M3 positions a water molecule to protonate the departing alkoxide, stabilizing the leaving-group. Functionally, M3 substitutes for the arginine clamp in phosphoprotein phosphatases (PPP), revealing that these evolutionarily distinct phosphatase families have converged on the same chemical strategy through fundamentally different catalytic architectures. Together, these findings define a three-metal mechanism in PPM phosphatases and identify the M3 site as a rare and potentially druggable feature for immune and infectious diseases.

biochemistry↗

bioRxiv2026

Dietary tryptophan mitigates lung ischemia-reperfusion injury via microbiota-derived indole-3-propionate and aryl hydrocarbon receptor signaling

BackgroundLung ischemia-reperfusion (IR) injury drives early morbidity after lung transplantation and cardiothoracic surgery, yet targeted preventive therapies are lacking. The gut-lung axis and microbiota-derived tryptophan metabolites, including indole-3-propionate (IPA), may regulate pulmonary immunity and inflammation. We investigated whether a tryptophan-rich (Trp-Rich) diet attenuates sterile lung IR injury by increasing microbiota-derived indole metabolites and reprogramming alveolar macrophage (AM) inflammatory responses. MethodsC57BL/6 mice received isocaloric tryptophan-standard (Trp-Std; 0.18%) or Trp-Rich (0.60%) diets for 14 days, then underwent unilateral left lung IR (60 min ischemia followed by 60 min reperfusion). Oxygen saturation, lung cytokines, and aryl hydrocarbon receptor (AhR) signaling readouts (Cyp1a1/Cyp1b1) were evaluated. Gut microbiota was profiled by 16S rRNA sequencing, and targeted metabolomics quantified tryptophan metabolites in feces, portal vein (PV) plasma, and lung tissue. To further assess inflammatory priming in vivo, mice were additionally challenged with intratracheal lipopolysaccharide (LPS). Mechanistic studies compared IPA with related indole metabolites in MH-S cells and primary human AMs, including ex vivo nutritional IR, LPS stimulation, and AhR stimulation and blockade using synthetic agonists and antagonists. ResultsTrp-Rich feeding improved post-IR oxygenation, reduced lung IL-1{beta}, and increased pulmonary Cyp1a1/Cyp1b1 gene expression. Trp-Rich diet remodeled the gut microbiota, including enrichment of Bifidobacterium and Lactobacillus, and increased IPA levels across feces, PV plasma, and lung tissue, with lower kynurenine/IPA ratios across matrices. In the LPS intratracheal challenge, Trp-Rich feeding reduced IL-6 levels in lung tissue and systemic plasma. Primary murine AMs isolated from Trp-Rich mice also showed reduced IL-1{beta} and IL-6 release in an ex vivo nutritional IR model. Among tested indole metabolites, IPA showed the strongest dose-dependent suppression of LPS-induced cytokines and chemokines in MH-S cells and primary human AMs, remained active in the ex vivo nutritional IR model, and its anti-inflammatory effect was abrogated by AhR blockade and enhanced by co-treatment with other indole metabolites. ConclusionsA Trp-Rich diet attenuated sterile lung IR injury, coinciding with gut microbiota remodeling, increased systemic and pulmonary IPA, reduced inflammatory priming, and reprogrammed AM responses. These data support diet- or microbiome-directed strategies targeting IPA-AhR signaling to mitigate perioperative lung IR injury. Caption for graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=190 SRC="FIGDIR/small/714281v1_ufig1.gif" ALT="Figure 1"> View larger version (67K): org.highwire.dtl.DTLVardef@1762c91org.highwire.dtl.DTLVardef@1681386org.highwire.dtl.DTLVardef@1da00aforg.highwire.dtl.DTLVardef@162f17f_HPS_FORMAT_FIGEXP M_FIG A tryptophan-rich diet remodels the gut microbiota and indole metabolite profiles, including IPA, enhances alveolar macrophage AhR signaling, and attenuates sterile lung ischemia-reperfusion injury. C_FIG

immunology↗

bioRxiv2026

Filopodia-mediated trans-endocytosis

Cell-cell communication in tissues is influenced by contact geometry and molecular signalling. Here, we demonstrate that epithelial intercellular filopodia can penetrate neighbouring cells to form micrometre-long, double-membrane "impact sites" and, in some instances, initiate trans-endocytosis. Using super-resolution live imaging and three-dimensional electron microscopy in cell models, xenografts, and patient-derived tissues, we observe widespread intercellular filopodia and extensive interdigitation at the cell-cell interface. Filopodia impact sites in the recipient cell recruit PACSIN2 into dynamic "PACSIN2 fingers" and are specifically enriched for caveolin-1 and dynamin-2, while clathrin and CLIC pathway markers are not enriched. Most contacts are transient and resolved by retraction, but some undergo scission, with recipient cells internalising filopodial tips across both homotypic and heterotypic interactions, including cancer-endothelium contacts. Correlative light and FIB-SEM analysis reveals that internalised tips are often double-membraned, closely associated with endoplasmic reticulum tubules, and can traffic to lysosomes. These findings define a protrusion-driven, curvature-dependent uptake pathway at cell-cell interfaces and identify filopodia as exchange organelles in epithelial collectives.

cell biology↗

bioRxiv2026

Tissue-scale mechanics controls differentiation strategy and dynamics of epithelial multilayering

Generating and maintaining multilayered epithelia requires coordinated cell division, differentiation, and tissue architecture, yet the precise mechanisms of multilayering remain unclear. Using the developing mouse epidermis, we show that basal stem cells adopt distinct multilayering strategies depending on tissue mechanics. Combining quantitative morphometry, embryo live imaging and physical modeling, we observe that early in development, the epidermis is fluid-like, allowing undifferentiated cells to move suprabasally through perpendicular divisions or basal detachment before differentiating. As the tissue matures and rigidifies, a mechanical barrier is established that only allows upward movement of basal cells that have committed to differentiation. The final step of this commitment is delamination that requires Notch signaling, triggered by increased tissue stiffness and jamming. This mechanical regulation orchestrates a feedback loop that induces cell upward motion precisely when the basal layer becomes crowded. Together, our findings identify tissue mechanics as the key determinant of how tissues drive multilayering and reveal mechanically regulated Notch signaling as a driver of epidermal delamination.

cell biology↗

bioRxiv2025

Transcriptional control of neuronal maintenance by SOX2 during inner ear innervation

The cochlear sensory epithelium and the spiral ganglion neurons it supports arise from a common pool of otic progenitors, yet the neurons remain dependent on the epithelium for guidance and survival long after the two lineages diverge. How that dependency is sustained as the progenitor pool generates increasingly restricted cell types is unknown. Here we show that SOX2 maintains this regulatory continuity. Deletion of Sox2 from the cochlear epithelium after cochlear neurogenesis does not affect neuroblast generation, delamination and proliferation; however, peripheral axons failed to reach the epithelium and neurons were progressively lost, identifying a non-cell-autonomous requirement for epithelial SOX2. Transcriptomic profiling revealed a SOX2-dependent epithelial programme enriched for neurotrophic and axon-guidance genes, including Ntf3 and Bdnf. In cochlear organoids, acute Sox2 deletion reduced H3K27ac at regulatory elements while H3K4me1 remained stable, consistent with SOX2 maintaining the activity of previously marked enhancers. Ntf3 and Bdnf exemplified distinct regulatory trajectories. At Ntf3, SOX2 occupied an enhancer whose activity depended on Sox2, whereas at Bdnf it occupied promoter-proximal elements in progenitors before ATOH1 engaged these and a hair-cell-active distal enhancer. Thus, SOX2 links sensory fate specification to epithelial-neuronal communication. More generally, our findings suggest that regulatory competence can persist through lineage restriction, while changing transcription-factor inputs partition its output among descendants to coordinate their development.

developmental biology↗

bioRxiv2025

Junctional Heterogeneity Shapes Epithelial Morphospace

Tissues and organs develop a wide range of shapes, sizes and cellular organisations, linked to their physiological function. How developmental programmes generate this organisational diversity remains poorly understood. Inner ear sensory epithelia in birds, fish, and mammals provide a tractable system to address this question, as their constituent cells arise from a common developmental lineage, share molecular signatures, and have conserved physiological functions, yet assemble into distinct cellular organisations. These epithelia contain two principal cell types, mechanosensory hair cells (HCs) and supporting cells (SCs), organised into mosaics. Here, we developed a three-parameter morphospace that quantitatively captures epithelial organisation, enabling comparisons across species, structures and developmental stages. Combining this framework with genetic perturbation, biochemical analysis and live imaging reveals that the diverse mature organisations emerge from a common early organisational state constrained by Notch-Delta signalling. During subsequent development, the differential localisation of adhesion molecules (Cdh1,2 and Nectin) and contractility-associated proteins (NM2 and -actinin-4) at HC-SC and SC-SC junctions establishes junctional asymmetries. Across species, asymmetry drives stable circular HCs and actively remodelling SCs. The coexistence of these cell shape states drives selective intercalation, guiding each epithelium along a distinct trajectory through morphospace toward its mature organisation. These findings identify cell-shape dynamics as a developmental mechanism for generating organisational diversity in sensory, and potentially other, epithelia.

developmental biology↗

bioRxiv2025

BC-Predict Database: A Curated Resource of Experimentally Validated Markers in Multidrug Resistance in Breast Cancer

BackgroundIn this study, we aim to develop a yearly updatable database that could predict chemotherapeutic drug resistance and overall survival probability in breast cancer patients. Existing drug sensitivity databases depend on correlation-based predictions. In our study, candidates involved in drug resistance are chosen based on cell line validation (overexpression or downregulation or inhibition of candidates) studies, curated manually. Method28,773 mRNA expression signatures from 914 breast cancer patients were extracted from cProsite. 106 of these patients had clinical information and log2 fold change information required for this study. We categorized these patients into deceased and surviving groups from TCGA. To prepare a database that can predict drug resistance and overall survival, we included mRNAs that were over-expressed in at least 80% of the breast cancer patients and mRNAs over-expressed in deceased and surviving groups. In addition, we also reported breast cancer-associated drug resistance candidates which have been reported in cell-line based studies. The database matrix preparation involved an approximate of 15000 manual searches of cell validated studies. (750 candidates x 20 drugs). The database was validated using a publicly available breast cancer patient proteomics data. ResultsOur analysis identified a list of top priority candidates associated with multidrug resistance, categorized based on their resistance to >15 drugs, 5-15 drugs, and 2-4 drugs. Analysis of patient profiles in the database revealed that the number of proteins contributing to drug resistance was high in the poor prognosis category compared to the good prognosis category. ConclusionsOur study highlights the probable gaps in breast cancer drug resistance research, as only a small subset of overexpressed mRNA candidates found in patients are studied in vitro or in vivo experiments focusing on drug resistance. We also identified candidates involved in multidrug resistance, whose role in drug resistance has not been studied in more than 15 drugs. After further validations, this will benefit the clinicians and upcoming CRISPR gene therapeutics.

cancer biology↗

bioRxiv2025

A developmental transition from early neural hyperexcitability in zebrafish

Early brain development is characterized by plastic phases that play a crucial role in the establishment of functional connectivity. However, this plasticity also renders the developing brain highly sensitive to perturbations. The dynamics of the transition of the immature brain from a hyperexcitable state to a relatively stable network remains poorly understood. Using a combination of brain-wide activity mapping, behavioural and molecular analysis in response to pentylenetetrazole (PTZ), a GABAA receptor antagonist, we assessed neural hyperexcitability at different developmental stages in larval zebrafish and observed a distinct age-dependent trajectory. Specifically, we observed that early stages (4-6 dpf) exhibited high susceptibility to external perturbations, whereas by 9 dpf, both neural activity and behavioral responses were markedly attenuated. Further, upon chronic insult, rather than a cumulative increase in excitability, early life hyperexcitation events rendered the larvae resistant to subsequent induction. Put together, our work maps the temporal transition of the vertebrate brain from a state of hyperexcitability to a phase of relative resistance and has potential implications on understanding the progression of neurological conditions in the pediatric population.

neuroscience↗

bioRxiv2025

Multi Omics Driven Polypharmacology for Osteoarthritis Joint Regeneration

Osteoarthritis (OA) is a common degenerative condition of major joints with no effective cure. Yograj Guggulu (YG) is a well-established polyherbal formulation in Indian traditional medicine for the management of joint disorders. However, its mode of action remains unclear. We integrated multi omics network analysis with a rat model to investigate the effects of oral administration of YG on osteoarthritic joints. YG administration significantly alleviated pain and improved joint function. Imaging and histological analyses reveal that YG protects against structural degeneration in the joint with OA. Proteomic and metabolomic profiling, along with network analysis, uncovered that multiple components of YG alter protein expression in key pathways related to inflammation and cartilage degradation, thus validating the observed clinical effects. The efficacy of YG seems to be the result of the synergistic action of its diverse constituents. Our findings support the use of YG as a multitarget therapy for OA and encourage efforts for the potential repurposing of its active components.

systems biology↗

bioRxiv2025

Force patterning drives cell flows and 3D spatial order in auditory epithelia

During development, coordinated cell behavior drives the morphogenesis of epithelia into intricate structures essential for their physiological functions. How this coordination is achieved in epithelia composed of multiple cell types remains unclear. We study development of the avian auditory epithelium comprising sensory hair cells (HCs) and non-sensory supporting cells (SCs). Initially, HCs and SCs are arranged into mosaics by Notch-Delta signaling. During development, HCs partially extrude from the epithelium, establish a ten-fold gradient in apical surface area across the tissue, and intercalate with SCs to form near-hexagonal order. Using a combination of experiments and a 3D-vertex model, we show that an increase of contractility at the apical junctions between SCs compared to those between HCs and SCs drives spatial order within the epithelial plane and along the apical-basal axis. A faster increase of HC apical area at one end of the epithelium than the other leads to opposite fluxes of HCs and SCs and establishes the observed gradients in apical surface area and density of HCs along the auditory epithelium while maintaining a uniform degree of hexagonal order throughout. Our findings reveal that patterned junctional contractility can spatially coordinate cell behavior across both the plane and depth of a mixed epithelium, providing a general mechanism for generating complex three-dimensional tissue architectures during organogenesis.

developmental biology↗

bioRxiv2025

Gut Microbiome-derived Propionate Reprograms Alveolar MacrophagesMetabolically and Regulates Lung Injury Responses

Responses to lung injury can vary between individuals and the diet and gut microbiome represent two underappreciated sources of inter-individual variability. The gut microbiome can influence lung injury outcomes through the gut-lung axis, but exactly how diet and its effects on the microbiota are involved remains unclear. We hypothesized that a dietary fiber intervention would enrich for the presence of short-chain fatty acid (SCFA)-producing fermentative bacteria in the gut microbiome, thereby influencing resting lung immunometabolic tone and influence downstream immune responses to lung injury and infection. To test this hypothesis, we fed mice fiber-rich (FR) and fiber-free (FF) diets and observed changes in the steady-state transcriptional programming of alveolar macrophages (AMs) in the absence of injury. Next, we examined the effects of FR and FF diets on the responses to sterile and infectious lung injury in vivo while simultaneously profiling gut microbiota and SCFA levels transmitted along the gut-lung axis. Finally, we validated our in vivo observations with mechanistic studies of the metabolic, signaling, and chromatin-modifying effects of specific SCFAs on lung AMs ex vivo and in vitro. Overall, a FR diet reprogrammed AMs and attenuated lung inflammation after sterile injury while exacerbating lung infection. This effect of FR diets could be transferred to germ-free (GF) mice by fecal microbiome transplantation (FMT) and depended on the ability of the microbiota to produce propionate. Mechanistically, SCFAs altered the metabolic programming of AMs and lung tissue ex vivo without a role for free fatty acid receptors (FFAR) or chromatin remodeling. These findings demonstrate that the gut-lung axis can regulate the resting metabolic tone through dietary fiber intake and the enrichment of SCFA-producing gut bacteria, as well as influence sterile and non-sterile lung injury responses through the activity of gut metabolites. These results provide further evidence to support the development of therapeutic dietary interventions or the use of specific gut metabolites to preserve or enhance specific aspects of host pulmonary immunity.

immunology↗

bioRxiv2025

Founders predict trait evolution and population dynamics after evolutionary rescue

Evolutionary rescue helps populations survive environmental change, but the phenotypic and demographic factors associated with rescue dynamics and its long-term effects remain unclear. We experimentally evolved 10 wild-collected populations of flour beetles from across India in a suboptimal corn resource for 70 generations (>5 years), collecting >10,000 population census points book-ended by measurements of fitness-related traits for 30 experimental lines. Despite clear ancestral trait differences, all lines showed highly parallel evolutionary rescue within 20 generations. Long-term average population size varied across source populations and was positively correlated with ancestral development rate, which increased convergently across populations and emerged as the single best predictor of population performance during and after evolutionary rescue. Notably, specific demographic events during rescue (such as the rate of population decline and recovery) were uncorrelated both with ancestral trait distributions and post-rescue adaptation. Our results support prior work showing founder traits as key predictors of adaptation, and highlight their role in long-term adaptation and trait evolution following evolutionary rescue. SIGNIFICANCE STATEMENTUnderstanding how populations adapt to sudden environmental change is vital given accelerating biodiversity declines, the rise of antimicrobial resistance and climate change. We chart evolutionary rescue -- where rapid adaptation prevents extinction -- in flour beetles across 70 generations. Using >10,000 census points and measuring fitness in ancestors, their offspring and in evolved lines, we show that larval development rate is the strongest correlate of long-term population success across diverse wild-collected populations. The effect of ancestral variation is dynamic and disassociated from finer-grained details of the rescue. All populations show highly parallel evolutionary rescue, with convergent evolution in key traits. These findings have direct implications for predicting species survival after environmental change, ranging from conservation to pest and pathogen management.

evolutionary biology↗

bioRxiv2025

AGAAT: Automated computational tool integrating different genotyping array and correctional methods for data analysis

Genotyping arrays are widely used in studying the genetics of complex diseases. Arrays with multi-ethnic markers enable population-scale and cost-effective genetic studies in underrepresented populations. But automated pipelines that convert raw data files into association results are lacking for these genotyping arrays. Also, combining variant files from multiple genotyping projects is difficult due to differences arising from multiple versions of standard file formats like Variant Calling Format (VCF). We have developed an automated tool named AGAAT (Automated Genotyping Array Analysis Tool) to overcome these problems. In addition to the automated pipelines for multi-ethnic arrays, we have added additional Python scripts for multiple testing correction using haplotype blocks, candidategene analysis, candidate-gene common-variant analysis and addition of 1000 genome phase-3 genotype counts to the controls, followed by case-control association analysis.

bioinformatics↗

bioRxiv2025

Neur-Ally: A deep learning model for regulatory variant prediction based on genomic and epigenomic features in brain and its validation in certain neurological disorders

Large scale quantitative studies have identified significant genetic associations for various neurological disorders. Expression quantitative trait loci [eQTL] studies have shown the effect of single nucleotide polymorphisms [SNPs] on the differential expression of genes in brain tissues. However, a large majority of the associations are contributed by SNPs in the noncoding regions which can have significant regulatory function but are often ignored. Besides mutations that are in high linkage disequilibrium [LD] with actual regulatory SNPs will also show significant associations. Therefore, it is important to differentiate a regulatory non-coding SNPs with a non-regulatory one. To resolve this, we developed a deep-learning model named Neur-Ally, which was trained on epigenomic datasets from nervous tissue and cell line samples. The model predicts differential occurrence of regulatory features like chromatin accessibility, histone modifications and transcription-factor [TF] binding on genomic regions using DNA sequence as input. The model was used to predict the regulatory effect of neurological condition specific non-coding SNPs using in-silico mutagenesis. The effect of associated SNPs reported in Genome-wide association studies [GWAS] of neurological condition, Brain eQTLs, Autism Spectrum Disorder [ASD] and reported probable regulatory SNPs in neurological conditions were predicted by Neur-Ally.

bioinformatics↗

bioRxiv2024

Role Of Pcdh15 In The Development Of Intrinsic Polarity Of Inner Ear Hair Cells

In vertebrates, auditory information is transduced in the cochlea by mechanosensory hair cells (HC) through an eccentrically organised structure known as the hair bundle. This consists of a true cilium, known as the kinocilium, and modified microvilli, known as stereocilia. The hair bundle has a distinct structure with stereocilia organised in graded rows, with the longest abutting the kinocilia. The hair bundles of all HC are aligned to the tissue axis and are planar polarised. Important in the development and physiology of HC are protein bridges consisting of cadherin-23 and protocadherin-15. These link the tips of stereocilia, where they play a role in mechanotransduction, and between the kinocilia and the stereocilia, where they are involved in development. Both cadherin-23 and protocadherin-15 mutations result in defects in planar polarity; however, the mechanism through which this defect arises is unclear. Using a novel mutant for the Pcdh15-CD2 isoform, we show that while the initial deflection of the kinocilium occurs, its peripheral migration to register with Gi3 is perturbed. Pcdh15-CD2 genetically interacts with Gpsm2, perturbing vestibular function. We find that the earliest expression of Pcdh15-CD2 is at the base of the kinocilia, and the defects in morphogenesis occur before the formation of kinocilial links. By re-introducing functional Pcdh15-CD2, we show that polarity can be restored, suggesting that Pcdh15-CD2 couples kinocilial and stereocilial development through a mechanism independent of kinocilial links.

developmental biology↗

bioRxiv2024

Early hominin arrival in Southeast Asia triggered the evolution of major human malaria vectors

Understanding the evolution of anthropophily, the preference of mosquitoes to feed on humans, offers insights into current and future human disease transmission. Some species of the Leucosphyrus Group of Anopheles mosquitoes in Southeast Asia are highly anthropophilic and efficient vectors of human malaria parasites, while others primarily feed on non-human primates and transmit non-human primate malaria parasites. Through phylogenomic analysis of 11 out of 20 recognized species, we studied the biogeography and evolutionary history of anthropophily in this group. Molecular dating and ancestral state reconstruction revealed that anthropophily evolved during the late Pliocene/early Pleistocene in Sundaland, likely in response to early hominins. This finding provides independent non-archaeological evidence supporting the limited fossil record of early hominin colonization in Southeast Asia around 1.8 million years ago.

evolutionary biology↗