Biology subjects

Ribeiro, R.

Publications and source records attributed to Ribeiro, R..

At least 19 recordsLinked to original sources

bioRxiv2026

PODXL regulates the neuronal entry of α-synuclein aggregates

Cell-to-cell transmission of -synuclein (-Syn) aggregates is a key event in Parkinson's disease (PD) pathogenesis, yet the neuronal surface factors that govern uptake of pathogenic -Syn fibrils remain undefined. We developed a flow cytometry-based CRISPR activation screen for modifiers of -Syn preformed fibril (PFF) uptake by human iPSC-derived cortical neurons. By interrogating 68 genes encoding cell-surface proteins prioritised by PD genetic associations, we identified podocalyxin-like protein 1 (PODXL) as a strong suppressor of -Syn fibril uptake. High-content imaging and PODXL cDNA overexpression confirmed reduced PFF uptake. Stable PODXL overexpression also reduced PFF-seeded pSynSer129 accumulation and uptake of structurally distinct recombinant and disease-derived -Syn fibrils. Conversely, shRNA-mediated PODXL knockdown increased -Syn PFF uptake, and analysis of PODXL domain-deletion and N-glycosylation mutants suggested that the ectodomain and N-glycosylation contribute to the PODXL-mediated reduction in uptake. Transcriptomic profiling further identified membrane metalloendopeptidase (MME) as a PODXL-responsive candidate mediator. MME activation and treatment with conditioned medium from MME-activated neurons reduced PFF uptake. Thiorphan, an MME inhibitor, partially attenuated the PODXL-associated reduction in uptake. Together, our findings identify PODXL as a neuronal brake on -Syn uptake and implicate its glycan-dependent surface properties together with MME-associated extracellular activity.

neuroscience↗

bioRxiv2026

Sugarcane's drought memory legacy: how past stress shapes future resilience

Plants frequently experience recurrent drought events separated by periods of rehydration. Although drought imposes strong constraints on plant physiology, prior exposure may alter subsequent stress responsiveness through memory-based mechanisms. Here, we investigated whether recurrent drought at distinct developmental stages establishes stress memory in sugarcane and whether this response persists across vegetative propagation. Two genotypes contrasting in drought tolerance and productivity (IACCTC07-8008 and IACSP95-5000, respectively) were grown under greenhouse conditions and subjected to three drought cycles imposed either at tillering or maturation stage. Gas exchange, photochemical performance, leaf water status, primary metabolite profile, and growth traits were assessed across cycles, and vegetative propagules were subsequently evaluated under renewed drought. The first drought cycle imposed strong limitations on carbon assimilation and photochemistry in both genotypes and developmental stages. However, subsequent cycles resulted in attenuated reductions in A and g, improved intrinsic water use efficiency, and partial stabilization of PSII performance, indicating a modified stress-response trajectory. Young plants displayed earlier improvements (from the second cycle), whereas in mature plants this shift was evident mainly during the third cycle. Recurrent drought promoted sustained reorganization of amino acid, carbohydrate, organic acid and polyol metabolism alongside increased root biomass and higher relative water content during later cycles. Importantly, propagules derived from drought-conditioned plants exhibited faster recovery of photosynthetic performance and reduced cumulative physiological impairment under renewed drought, despite showing similar stress sensitivity at maximum water deficit. This persistence of enhanced recovery capacity across vegetative propagation indicates that drought-induced memory was maintained beyond the initially stressed plants. Together, our findings demonstrate that recurrent drought establishes a metabolically imprinted state in clonal sugarcane, integrating physiological adjustment, metabolic reprogramming, and whole-plant acclimation. These results highlight the potential of stress memory as a mechanism supporting resilience in perennial crops exposed to increasingly recurrent drought events.

plant biology↗

bioRxiv2026

Continuous monitoring of plant transpiration dynamics with a leaf-mounted sensor across environmental conditions

O_LITranspiration plays a central role in plant water relations and strongly influences plant growth. Continuous monitoring is essential for understanding responses to environmental conditions and improving water management in both natural and agricultural systems. Gas-exchange techniques such as infrared gas analysers (IRGAs) and porometers are widely used but are challenging for long-term or large-scale monitoring. On the other hand, the FylloClip is a low-cost, leaf-mounted capacitance sensor developed previously to monitor transpiration by detecting condensation of water vapour near the leaf surface. Here, we evaluated the potential of the FylloClip for monitoring transpiration dynamics and assessed environmental conditions that may affect its performance. C_LIO_LIThe FylloClip was tested under growth chamber, greenhouse, and tropical field conditions. We evaluated how its capacitance measurements respond to rainfall, temperature and humidity, and compared FylloClip measurements with transpiration measured with an IRGA. C_LIO_LIThere was a strong correlation (r = 0.85) between FylloClip and IRGA data. Both systems captured similar diurnal transpiration patterns, with transpiration declining simultaneously under water deficit. Rainfall and very high relative humidity produced FylloClip signals that could be misinterpreted as high transpiration, although transpiration is negligible under these conditions. C_LIO_LIOur results revealed that FylloClips capture temporal patterns of transpiration with high accuracy and resolution, providing a reliable tool for long-term, large-scale monitoring of transpiration dynamics in ecophysiological studies and precision agriculture. C_LI

Plant Biology↗

bioRxiv2025

Spillover of H5 influenza viruses to vampire bats at the marine-terrestrial interface

The highly pathogenic H5N1 avian influenza A virus (IAV) clade 2.3.4.4b has spread globally and spilled over into multiple mammalian species, raising concerns about its pandemic potential. In late 2022, clade 2.3.4.4b viruses devastated seabird and marine mammal populations along the Pacific coast of South America. Here, we report the first evidence of H5 IAV infections in wild bats globally, focusing on common vampire bats (Desmodus rotundus) in coastal areas of Peru. Longitudinal serological screening, stable isotope analysis and metabarcoding revealed repeated exposures to H5 IAVs in vampire bats which feed on coastal wildlife species heavily impacted by the 2.3.4.4b epizootic, but no evidence of infection in populations without access to marine prey. We further report bat gene flow between IAV-exposed and IAV-naive populations, and IAV infections in a vampire bat colony that fed on both marine and terrestrial livestock prey, providing insights into how future IAV epizootics might spread spatially within bats and between marine and terrestrial ecosystems if a bat reservoir were established. Immunohistochemistry demonstrated that the H5 haemagglutinin protein binds to the upper respiratory tract of vampire bats, suggesting bat tissue susceptibility to H5 IAVs. Finally, vampire bat-derived kidney, liver, and lung cells supported entry, replication, and egress of avian and mammalian 2.3.4.4b viruses, confirming cellular infectivity. These results illustrate how combining ecological inference and experimental virology can pinpoint the species origins and biological significance of viral spillover at species interfaces. Recurrent exposures from marine wildlife, tissue and cellular susceptibility to H5N1 IAVs, and connections to other IAV-susceptible terrestrial mammals establish the prerequisite conditions for vampire bats to spread IAVs between marine and terrestrial environments or to form a novel reservoir of highly pathogenic IAVs.

ecology↗

bioRxiv2025

Lonafarnib Partially Reverses Cardiac Senescence in Human and Mouse Progeria Models via Autophagy Activation

Hutchinson-Gilford Progeria Syndrome (HGPS), characterised by accelerated ageing, causes cardiovascular defects resembling aspects of cardiovascular ageing. We used human left ventricle cardiomyocytes (CMs) derived from HGPS-induced pluripotent stem cells (iPSCs), and their isogenic-corrected controls, to investigate HGPS-CM dysfunction and identify potential therapies. Our results revealed that HGPS-iPSC-CMs exhibit greater maturity and associated elevated oxidative stress compared to controls, which they could not contend with, leading to cellular senescence. Increased senescence was also observed in cardiac tissue from mouse and human physiologically-aged and HGPS individuals. Functionally, HGPS-iPSC-CMs showed dysregulated mitochondrial respiration and calcium handling. Amongst the six drugs tested, rapamycin and lonafarnib were the most effective against HGPS-cardiac phenotypes. Although lonafarnib raised safety concerns, it partially reverted the cardiac senescent phenotype by inducing cellular autophagy and decreasing progerin expression in progeroid mice. Our study supports the use of HGPS-iPSC-CMs to identify novel biomarkers and therapies for HGPS, and potentially cardiac physiological-ageing.

cell biology↗

bioRxiv2025

Field-based prediction of sugarcane photosynthesis through environmental inputs

Sugarcane (Saccharum officinarum) is a highly productive C4 crop prevalent in tropical and subtropical areas. However, its photosynthetic efficiency is influenced by environmental factors such as light, moisture and temperature. Understanding these interactions is critical for optimizing yields and addressing climate-related challenges. This study investigated the effects of environmental variables on carbon assimilation in four Brazilian sugarcane varieties (SP79-1011, IAC94-2094, IACSP94-2101 and IACSP95-5000), addressing both optimal and limiting conditions for key parameters. Over a 530-day field experiment, data were collected every 30 days from 7:00 to 17:00, measuring diurnal CO2 assimilation (A), photosynthetically active radiation (PAR), vapor pressure deficit (VPD), and air temperature. Polynomial models and multiple linear regression were used to quantify the contributions of these variables in CO2 uptake, yielding robust model fits (p<0.05, R2 = 0.84-0.99). Herein, optimal photosynthetic performance occurred under PAR at 1800 mol m-2 s-1, VPD at 2.34 kPa, and air temperature close to 32.5{degrees}C. A strong correlation (r = 0.92, p<0.001) between observed and predicted photosynthesis and high model efficacy (R2=0.60, p<0.001) underscored the reliability of the approach, explaining 60% of the observed variation. While the results highlighted the models effectiveness in predicting sugarcane photosynthetic rates under varying diurnal and seasonal conditions, deviations indicated the influence of unmeasured parameters and complex interactions that need further investigation. These findings provide valuable insights to refine sugarcane management practices, enhance yield potential, and improve crop resilience under climate change scenarios.

plant biology↗

bioRxiv2024

Axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons

Sensory dorsal root ganglion (DRG) neurons have a unique pseudo-unipolar morphology in which a stem axon bifurcates into a peripheral and a central axon, with different regenerative abilities. Whereas peripheral DRG axons regenerate, central axons are unable to regrow. Central axon regeneration can however be elicited by a prior conditioning lesion to the peripheral axon. How DRG axon asymmetry is established, remains unknown. Here we developed a rodent in vitro system replicating DRG pseudo-unipolarization and asymmetric axon regeneration. Using this model, we observed that from early development, central DRG axons have a higher density of growing microtubules. This asymmetry was also present in vivo and was abolished by a conditioning lesion that decreased microtubule polymerization of central DRG axons. An axon-specific microtubule-associated protein (MAP) signature, including the severases spastin and katanin and the microtubule regulators CRMP5 and tau, was found and shown to adapt upon conditioning lesion. Supporting its significance, interfering with the DRG MAP signature either in vitro or in vivo, readily abolished central-peripheral asymmetries in microtubule dynamics and regenerative ability. In summary, our data unveil that axon-specific microtubule regulation drives asymmetric regeneration of sensory neuron axons. Impact statementSensory neurons have a stem axon that bifurcates originating two axons with different properties. This work shows that DRG axons have a specific protein signature underlying microtubule and regeneration asymmetries. It also provides an in vitro system replicating DRG biology.

neuroscience↗

bioRxiv2024

Modeling suggests SARS-CoV-2 rebound after nirmatrelvir-ritonavir treatment is driven by target cell preservation coupled with incomplete viral clearance

In a subset of SARS-CoV-2 infected individuals treated with the oral antiviral nirmatrelvir-ritonavir, the virus rebounds following treatment. The mechanisms driving this rebound are not well understood. We used a mathematical model to describe the longitudinal viral load dynamics of 51 individuals treated with nirmatrelvir-ritonavir, 20 of whom rebounded. Target cell preservation, either by a robust innate immune response or initiation of nirmatrelvir-ritonavir near the time of symptom onset, coupled with incomplete viral clearance, appear to be the main factors leading to viral rebound. Moreover, the occurrence of viral rebound is likely influenced by time of treatment initiation relative to the progression of the infection, with earlier treatments leading to a higher chance of rebound. Finally, our model demonstrates that extending the course of nirmatrelvir-ritonavir treatment, in particular to a 10-day regimen, may greatly diminish the risk for rebound in people with mild-to-moderate COVID-19 and who are at high risk of progression to severe disease. Altogether, our results suggest that in some individuals, a standard 5-day course of nirmatrelvir-ritonavir starting around the time of symptom onset may not completely eliminate the virus. Thus, after treatment ends, the virus can rebound if an effective adaptive immune response has not fully developed. These findings on the role of target cell preservation and incomplete viral clearance also offer a possible explanation for viral rebounds following other antiviral treatments for SARS-CoV-2. ImportanceNirmatrelvir-ritonavir is an effective treatment for SARS-CoV-2. In a subset of individuals treated with nirmatrelvir-ritonavir, the initial reduction in viral load is followed by viral rebound once treatment is stopped. We show the timing of treatment initiation with nirmatrelvir-ritonavir may influence the risk of viral rebound. Nirmatrelvir-ritonavir stops viral growth and preserves target cells but may not lead to full clearance of the virus. Thus, once treatment ends, if an effective adaptive immune response has not adequately developed, the remaining virus can lead to rebound. Our results provide insights into the mechanisms of rebound and can help develop better treatment strategies to minimize this possibility.

immunology↗

bioRxiv2024

Cigarette smoking drives accelerated aging across human tissues

Tobacco smoke is the main cause of preventable mortality worldwide. Smoking increases the risk of developing many diseases and has been proposed as an aging accelerator. Yet, the molecular mechanisms driving smoking-related health decline and aging acceleration in most tissues remain unexplored. Here, we characterize gene expression, alternative splicing, DNA methylation and histological alterations induced by cigarette smoking across human tissues. We show that smoking impacts tissue architecture and triggers systemic inflammation. We find that in many tissues, the effects of smoking significantly overlap those of aging in the same direction. Specifically, both age and smoking upregulate inflammatory genes and drive hypomethylation at enhancers. In addition, we observe widespread smoking-driven hypermethylation at target regions of the Polycomb repressive complex, which is a well-known aging effect. Smoking-induced epigenetic changes overlap causal aging CpGs, suggesting that these methylation changes may directly mediate aging acceleration observed in smokers. Finally, we find that smoking effects that are shared with aging are more persistent over time. Overall, our multi-tissue and multi-omic analysis of the effects of cigarette smoking provides an extensive characterization of the impact of tobacco smoke across tissues and unravels the molecular mechanisms driving smoking-induced tissue homeostasis decline and aging acceleration.

bioinformatics↗

bioRxiv2023

Xylem sap residue in cut-open conduits can affect gas discharge in pneumatic experiments

O_LIConsiderable progress has been made in understanding the mechanisms of embolism formation based on the pneumatic method, which relies on gas discharge measurements. Here, we test the assumption that cut-open conduits are gas-filled when samples are cut at high water potentials. C_LIO_LIWe performed vulnerability curves (VC) with the Pneumatron and analysed sap extraction from cut-open vessels in Citrus branches, while the optical method was applied as a reference method. VCs of 11 additional angiosperms were analysed to generalise our findings. C_LIO_LIWe found an increase in gas discharge during early stages of dehydration, which affected the VC of Citrus. Xylem sap was not absorbed immediately by surrounding tissue in cut Citrus branches. The gas amount discharged increased until all sap residue was absorbed, which was near the turgor loss point. By analysing the slope of VCs, we could correct pneumatic VC, as evidenced by the strong agreement in embolism resistance between the pneumatic and the optical method. C_LIO_LISince residual sap in cut-open conduits of some species could slightly reduce embolism resistance in some species, we propose to apply an easy correction for this novel artefact. Automated measurements with a Pneumatron are also required because of its high time resolution. C_LI

plant biology↗

bioRxiv2023

Incorporating environmental heterogeneity and observation effort to predict host distribution and viral spillover from a bat reservoir.

Predicting the spatial occurrence of wildlife is a major challenge for ecology and management. In Latin America, knowledge of the true number and locations of vampire bat colonies precludes informed allocation of measures intended to limit lethal rabies spillover to humans and livestock. We inferred the complete spatial distribution of vampire bat roosts while accounting for observation effort and environmental covariates by fitting a Log Gaussian Cox Process model to the locations of 563 roosts in three regions of Peru. Our model explained 47% of the variance in the observed roost distribution and identified landscape correlates of roost establishment. Our model estimated that 1,795 roosts (76%) remain undiscovered and identified hotspots of undetected roosts in currently rabies-free areas, implying high risk for viral incursion. Incorporating the locations of undetected roosts improved spatial predictions of rabies spillover to livestock, revealed areas with disproportionate underreporting to surveillance systems, and indicated a higher rabies burden than previously estimated. We provide a robust approach to infer the distribution of a mostly unobserved bat reservoir that can inform strategies to prevent the re-emergence of an important zoonosis.

ecology↗

bioRxiv2023

Idioblasts accumulating anticancer alkaloids in Catharanthus roseus leaves are a unique cell type

Catharanthus roseus leaves produce a range of monoterpenoid indole alkaloids (MIAs) that include low levels of the anticancer drugs vinblastine and vincristine. The MIA pathway displays a complex architecture spanning different subcellular and cell-type localizations and is under complex regulation. As a result, the development of strategies to increase the levels of the anticancer MIAs has remained elusive. The pathway involves mesophyll specialised idioblasts where the late unsolved biosynthetic steps are thought to occur. Here, protoplasts of C. roseus leaf idioblasts were isolated by fluorescence-activated cell sorting, and their differential alkaloid and transcriptomic profiles were characterised. This involved the assembly of an improved C. roseus transcriptome from short- and long-read data, IDIO+. It was observed that C. roseus mesophyll idioblasts possess a distinctive transcriptomic profile associated with protection against biotic and abiotic stresses, and indicative that this cell type is a carbon sink, in contrast with surrounding mesophyll cells. Moreover, it is shown that idioblasts are a hotspot of alkaloid accumulation, suggesting that their transcriptome may hold the keys to the in-depth understanding of the MIA pathway and the success of strategies leading to higher levels of the anticancer drugs. HighlightCatharanthus mesophyll idioblasts are a hotspot of anticancer alkaloid accumulation. The idioblast transcriptome reveals commitment with stress responses and provides a roadmap towards the increase of anticancer alkaloid levels.

plant biology↗

bioRxiv2022

Dynamic changes in gas solubility of xylem sap reiterate the enigma of plant water transport under negative pressure

Despite a long research history, we do not fully understand why plants are able to transport xylem sap under negative pressure without constant failure. Microbubble formation via direct gas entry is assumed to cause hydraulic failure, while the concentration of gas dissolved in xylem sap is traditionally supposed to be constant, following Henrys law. Here, the concentration of soluble gas in xylem sap was estimated in vivo using well-watered Citrus plants under varying levels of air temperature and photoperiodic exposure, and compared to modelled data. The gas concentration in xylem sap showed non-equilibrium curves, with a minimum over- or undersaturation of 5% compared to gas solubility based on Henrys law. A similar diurnal pattern was obtained from the gas concentration in the cut-open conduits and discharge tube, and oversolubility was strongly associated with decreasing xylem water potentials during transpiration. Although our model did not explain the daily changes in gas solubility for an anisobaric situation, oversolubility characterises nanoconfined liquids, such as sap inside cell walls. Thus, plants are able to transport sap under negative pressure with relatively high amounts of dissolved gas, providing them with a buffering capacity to prevent hydraulic failure, despite diurnal changes in pressure and temperature.

plant biology↗

bioRxiv2021

Gut microbiota diversity and C-Reactive Protein are predictors of disease severity in COVID-19 patients

Risk factors for COVID-19 disease severity are still poorly understood. Considering the pivotal role of gut microbiota on host immune and inflammatory functions, we investigated the association between changes in gut microbiota composition and the clinical severity of COVID-19. We conducted a multicentre cross-sectional study prospectively enrolling 115 COVID-19 patients categorized according to: 1) WHO Clinical Progression Scale - mild 19 (16.5%), moderate 37 (32.2%) or severe 59 (51.3%); and 2) location of recovery from COVID-19 - ambulatory 14 (household isolation; 12.2%), hospitalized in ward 40 (34.8%) or intensive care unit 61 (53.0%). Gut microbiota analysis was performed through 16S rRNA gene sequencing and data obtained was further related with clinical parameters of COVID-19 patients. Risk factors for COVID-19 severity were identified by univariate and multivariable logistic regression models. In comparison with mild COVID-19 patients, the gut microbiota of moderate and severe patients has: a) lower Firmicutes/Bacteroidetes ratio, b) higher abundance of Proteobacteria; and c) lower abundance of beneficial butyrate-producing bacteria such as Roseburia and Lachnospira genera. Multivariable regression analysis showed that Shannon index diversity (odds ratio [OR] 2.85 [95% CI 1.09-7.41]; p=0.032) and C-Reactive Protein (OR 3.45 [95% CI 1.33-8.91]; p=0.011) were risk factors for COVID-19 severe disease (a score of 6 or higher in WHO clinical progression scale). In conclusion, our results demonstrated that hospitalised moderate and severe COVID-19 patients have microbial signatures of gut dysbiosis and for the first time, the gut microbiota diversity is pointed out as a prognostic biomarker for COVID-19 disease severity.

microbiology↗

bioRxiv2021

A Unit Pipe Pneumatic model to simulate gas kinetics during measurements of embolism in excised angiosperm xylem

O_LIThe Pneumatic method has been introduced to quantify embolism resistance in plant xylem of various organs. Despite striking similarity in vulnerability curves between the Pneumatic and hydraulic methods, a modeling approach is highly needed to demonstrate that xylem embolism resistance can be accurately quantified based on gas diffusion kinetics. C_LIO_LIA Unit Pipe Pneumatic (UPPn) model was developed to estimate gas diffusion from intact conduits, which were axially interconnected by interconduit pit membranes. The physical laws used included Ficks law for diffusion, Henrys law for gas concentration partitioning between liquid and gas phases at equilibrium, and the ideal gas law. C_LIO_LIThe UPPn model showed that 91% of the extracted gas came from the first two series of embolized, intact conduits, and only 9% from the aqueous phase after 15 s of simulation. Embolism resistance measured with a Pneumatic apparatus was systematically overestimated by 2 to 17%, corresponding to a typical measuring error of 0.11 MPa for P50 (the water potential equivalent to 50% of the maximum amount of gas extracted). C_LIO_LIBecause results from the UPPn model are supported by experimental evidence, there is a good theoretical and experimental basis for applying the pneumatic method to research on embolism resistance of angiosperms. C_LI

plant biology↗

bioRxiv2020

A semi-automated method for measuring xylem vessel length distribution

Knowledge about the length of xylem vessels is essential to understand water transport in plants because these multicellular units show a 100-fold variation, from less than a centimeter to many meters. However, the available methods to estimate vessel length distribution (VLD) are excessively time consuming and do not allow large and in-depth surveys. Here, we describe a semi-automated method to measure VLD using an automated Pneumatron device. Gas conductivity of a xylem tissue with a certain length is estimated in a straightforward and precise way with the Pneumatron in a way theoretically similar to the air-injection method. The method presented enables fast and easy measurements using multiple devices simultaneously (>50 samples day-1), which is a significant advantage. Here, the apparatus is described in detail as well as how measurements are taken. We also present the software and an R-script for data analysis. The method described represents an important contribution to studies on plant hydraulic architecture and can improve our understanding about the role of VLD in plant performance under varying water availability.

plant biology↗

bioRxiv2019

Influence of selective treatment on Haematobia irritans infestation of untreated cattle

To reduce the use of insecticide treatments against Haematobia irritans we evaluated the impact of treating 15% of the bovines, with the greatest number of flies including bulls, with 40% diazinon ear tags, on the infestation of untreated cows. Horn fly susceptibility to diazinon was measured before and after treatment, and peaks of infestation were recorded. Three groups of Bradford bovines were evaluated: Group 1 (control untreated), Group 2 (15% treated) and Group 3 (control 100% treated). Weekly counts of horn flies were performed on the same animals for 78 days. Two peaks of infestation were recorded, and a higher number of horn flies occurred in the untreated control group than in the untreated cows of the selectively treated group throughout the entire period of the study, except for a single week. The horn fly field population was significantly more susceptible to diazinon than the reference susceptible strain both before and after insecticide treatment. In conclusion, treatment of 15% of the most infested animals from a herd, with 40% diazinon ear tags, quickly reduced horn fly infestations of the entire herd and may be a practical approach for horn fly control, reducing costs and chemical use.

ecology↗

bioRxiv2019

The dopamine receptor D5 gene shows signs of independent erosion in Toothed and Baleen whales

To compare gene loci considering a phylogenetic framework is a promising approach to uncover the genetic basis of human diseases. Imbalance of dopaminergic systems is suspected to underlie some emerging neurological disorders. The physiological functions of dopamine are transduced via G-protein-coupled receptors, including DRD5 which displays a relatively higher affinity towards dopamine. Importantly, DRD5 knockout mice are hypertense, a condition emerging from an increase in sympathetic tone. We investigated the evolution of DRD5, a high affinity receptor for dopamine, in mammals. Surprisingly, among 124 investigated mammalian genomes, we found that Cetacea lineages (Mysticeti and Odontoceti) have independently lost this gene, as well as the burrowing Chrysochloris asiatica (Cape golden mole). We suggest that DRD5 inactivation parallels hypoxia-induced adaptations, such as peripheral vasoconstriction required for deep-diving in Cetacea, in accordance with the convergent evolution of vasoconstrictor genes in hypoxia-exposed animals. Our findings indicate that Cetacea are natural knockouts for DRD5 and might offer valuable insights into the mechanisms of some forms of vasoconstriction responses and hypertension in humans.

evolutionary biology↗