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Search indexed bioRxiv preprints in genomics, neuroscience, cell biology and bioinformatics. Read source abstracts and check manuscript versions; preprints are not peer reviewed.

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bioRxiv2018

Distinctive interaction between cognitive networks and the visual cortex in early blind individuals

In early blind individuals, brain activation by a variety of non-perceptual cognitive tasks extends to the visual cortex, while in the sighted it is restricted to supramodal association areas. We hypothesized that such activation results from the integration of different sectors of the visual cortex into typical task-dependent networks. We tested this hypothesis with fMRI in blind and sighted subjects using tasks assessing speech comprehension, incidental long-term memory and both verbal and non-verbal executive control, in addition to collecting resting-state data. All tasks activated the visual cortex in blind relative to sighted subjects, which enabled its segmentation according to task sensitivity. We then assessed the unique brain-scale functional connectivity of the segmented areas during resting state. Language-related seeds were preferentially connected to frontal and temporal language areas; the seed derived from the executive task was connected to the right dorsal frontoparietal executive network; the memory-related seed was uniquely connected to mesial frontoparietal areas involved in episodic memory retrieval. Thus, using a broad set of language, executive, and memory tasks in the same subjects, combined with resting state connectivity, we demonstrate the selective integration of different patches of the visual cortex into brain-scale networks with distinct localization, lateralization, and functional roles.

neuroscience↗

bioRxiv2018

Correlation of occludin protein mobility with paracellular leak pathway permeability in renal epithelia

Studies have demonstrated regulation of the epithelial paracellular permeability barrier, the tight junction, by a variety of stimuli. Recent studies have reported a correlation between changes in paracellular permeability, particularly paracellular permeability to large solutes (leak pathway), and mobility of the tight junction protein, occludin, in the plane of the plasma membrane. This had led to the hypothesis that changes in occludin protein mobility are causative for changes in paracellular permeability. Using a renal epithelial cell model system, MDCK, we examined the effect of various manipulations on both leak pathway permeability, monitored as the paracellular movement of a fluorescent molecule (calcein), and occludin protein mobility, monitored through fluorescence recovery after photobleaching. Our results indicate that knockdown of the associated tight junction protein, ZO-1, increases baseline leak pathway permeability, whereas, knockdown of the related tight junction protein, ZO-2, does not alter baseline leak pathway permeability. Knockdown of either ZO-1 or ZO-2 decreases the rate of movement of occludin protein but only knockdown of ZO-2 protein alters the percent of occludin protein that is mobile. Further, treatment with hydrogen peroxide increases leak pathway permeability in wild type MDCK cells and in ZO-2 knockdown MDCK cells but not in ZO-1 knockdown MDCK cells. This treatment decreases the rate of occludin movement in all three cell lines but only alters the mobile fraction of occludin protein in ZO-1 knockdown MDCK cells. Finally, we examined the effect of renal ischemia/reperfusion injury on occludin protein mobility in vivo.\n\nIschemia/reperfusion injury both increased the rate of occludin mobility and increased the fraction of occludin protein that is mobile. These results indicate that, at least in our cell culture and in vivo model systems, there is no consistent correlation between paracellular leak pathway permeability and occludin protein mobility.

physiology↗

bioRxiv2018

Absence of general rules governing molluscan body-size response to climatic fluctuation during Cenozoic

Body size is a key factor in dictating the fate of interaction between an organism and its surrounding environment. A negative temperature-size relationship (TSR) has been suggested as one of the universal responses to climatic warming. It is also predicted that groups with narrow latitudinal range, tropical affinity and higher body size, would show higher sensitivity to climatic fluctuation. Moreover, because of the difference in thermal sensitivity, it is also expected that the response to climatic fluctuation would be different between epifaunal and infaunal groups. To confirm the generality of these relationship among marine families, we compiled the relationship between body-size and global temperature trends over Cenozoic using a database of marine benthic molluscs of class gastropoda and bivalvia resolved to temporal stages. We evaluated the dependence of climate induced body-size response to the existing size and latitudinal spread via correlating the first-difference correlation coefficient of temperature-size ({rho}1st (size-temp)) with maximum size and latitudinal spread of family respectively. Cenozoic record of this highly diverse group does not show any signature of TSR for molluscan class or for any other regional, ecological groups during the past 66My long climatic fluctuation. We did not find any evidence supporting heightened response to climatic fluctuation in groups with limited latitudinal spread or with large body-size. The tropical species did not show significant difference in their body-size response in comparison to temperate species. It also shows lack of any difference in response between ecological groups of molluscs with varying substrate relationship and hence, refutes the predicted variation due to difference in thermal specialization. Although a negative correlation between maximum latitudinal spread and {rho}1st (size-temp) is observed for infaunal families, it is not statistically significant. Our results highlight the limited validity of \"universal rules\" in explaining the climate induced morphological response of marine communities in deep time and underscores the complexity in generalizing the biotic outcome of future climatic fluctuation.

paleontology↗

bioRxiv2018

Estimation of auditory steady-state responses based on the averaging of independent EEG epochs

The amplitude of the auditory steady-state responses (ASSRs) generated in the brainstem exponentially decreases over the averaging of subsequent EEG epochs. This behavior is partially due to the adaptation of the auditory response to the continuous and monotonous stimulation. We analyzed the potential clinical relevance of the ASSR adaptation. Specifically, we compare the ASSR amplitude computed in two conditions: (1) when the auditory responses -embedded in the EEG epochs that are averaged in the estimation procedure- are influenced by the previous stimulation; and (2) when they are independent of the previous stimulation. ASSR were elicited in eight anesthetized adult rats by 8-kHz tones, modulated in amplitude at 115 Hz. ASSR amplitudes were computed using three averaging methods (standard, weighted and sorted averaging). We evaluated the ASSR amplitude as a function of sub-set of epochs selected for the averaging and the improvement in the ASSR detection resulting from averaging independent epochs. Due to adaptation, the ASSR amplitude computed by averaging dependent EEG epochs relied upon the averaging method. Lower ASSR amplitudes were obtained as EEG segments containing unadapted responses were systematically excluded from the averaging. In the absence of EEG artifacts, the ASSR amplitudes did not depend on the averaging method when they were computed from independent EEG epochs. The amplitude of independent ASSRs were up to 35% higher than those obtained by processing dependent EEG segments. Extracting the ASSR amplitude from independent epochs halved the number of EEG segments needed to be averaged to achieve the maximum detection rate of the response. Acquisition paradigm based on a discrete acoustic stimulation (in which segments of AM-sounds of several seconds in length are presented after a given inter stimulus interval), in combination with appropriated averaging methods might increase the accuracy of audiological tests based on ASSRs.

neuroscience↗

bioRxiv2018

Cerebral blood flow measured with diffusing wave spectroscopy during anesthesia

The adequate perfusion of the brain is of utmost importance where already short periods of hypoperfusion may lead to permanent damage. In order to increase patient safety the cerebral blood flow should be monitored in clinical settings during situations, such as anesthesia, where the perfusion might be disturbed. The cerebral blood flow is however not monitored on a routine basis during anesthesia. Diffusing wave spectroscopy is a relative novel optical method that non-invasively measures changes in cerebral blood flow. Here we report changes in cerebral blood flow associated with a delayed cardiac output, a change in isoflurane concentration and body temperature observed during general anesthesia with isoflurane in pigeons.

biophysics↗

bioRxiv2018

Robust Algorithms for Capturing Population Dynamics and Transport in Oceanic Variables along Drifter Trajectories using Linear Dynamical Systems with Latent Variables

The blooms of Noctiluca in the Gulf of Oman and the Arabian Sea have been intensifying in recent years posing a threat to regional fisheries and the long-term health of an ecosystem supporting a coastal population of nearly 120 million people. We present the results of a microscopic data analysis to investigate the onset and patterns of the Noctiluca (mixotrophic dinoflagellate Noctiluca scintillans) blooms, which form annually during the winter monsoon in the Gulf of Oman and in the Arabian Sea. Our approach combines methods in physical and biological oceanography with machine learning techniques. In particular, we present a robust algorithm, the variable-length Linear Dynamic Systems (vLDS) model, that extracts the causal factors and latent dynamics at the microscopic population-level along each individual drifter trajectory, and demonstrate its effectiveness by using it to test and confirm previously benchmarked macroscopic scientific hypotheses. The test results provide microscopic statistical evidence to support and recheck the macroscopic physical and biological Oceanography hypotheses on the Noctiluca blooms; it also helps identify complementary microscopic dynamics that might not be visible or discoverable at the macroscopic scale. The vLDS model also exhibits a generalization capability (inherited from a machine learning methodology) to investigate important causal factors and hidden dynamics associated with ocean biogeochemical processes and phenomena at the population-level.

ecology↗

bioRxiv2018

Inhibition of platelet function by targeting the platelet cytoskeleton via the LIMK-signaling pathway.

Actin is highly abundant in platelets, and platelet function is dependent on actin structures. Actin filaments are dynamic structures involved in many cellular processes including platelet shape changes and adhesion. The actin cytoskeleton is tightly regulated by actin-binding proteins, which include the members of the actin depolymerising factor (ADF)/cofilin family. LIM kinase (LIMK) and slingshot phosphatase (SSH-1L) regulate actin dynamics by controlling the binding affinity of ADF/cofilin towards actin. We hypothesised that inhibition of LIMK activity may prevent the changes in platelet shape during their activation and therefore their function by controlling the dynamics of Factin. Therefore, inhibition of LIMK activity may represent an attractive new strategy to control and inhibit platelet function; particularly the formation of stable platelet aggregates and thus stable thrombi.

cell biology↗

bioRxiv2018

Thermal acclimation of photosynthetic activity and Rubisco content in two hybrid poplar clones

The mechanistic bases of thermal acclimation of net photosynthetic rate (An) are still difficult to discern and empirical research remains limited, particularly for hybrid poplar. In the present study, we examined the contribution of a number of biochemical and biophysical traits on thermal acclimation of An for two hybrid poplar clones. We grew cuttings of Populus maximowiczii x Populus nigra (MxN) and Populus maximowiczii x Populus balsamifera (MxB) clones under two day/night temperature of 23{degrees}C/18{degrees}C and 33{degrees}C /27{degrees}C and under low and high soil nitrogen level. After 10 weeks, we measured leaf RuBisCO and RuBisCO activase (RCA) amounts and the temperature response of An, dark respiration (Rd), stomatal conductance, (gs), maximum carboxylation rate of CO2 (Vcmax) and photosynthetic electron transport rate (J). Results showed that a 10{degrees}C increase in growth temperature resulted in a shift in thermal optimum (Topt) of An of 6.2{+/-}1.6 {degrees}C and 8.0{+/-}1.2 {degrees}C for clone MxB and MxN respectively, and an increased An and gs at the growth temperature for clone MxB but not MxN. RuBisCO amount was increased by N level but was insensitive to growth temperature while RCA amount and the ratio of its short to long isoform was stimulated by warm condition for clone MxN and at low N for clone MxB. The activation energy of Vcmax and J decreased under warm condition for clone MxB and remain unchanged for clone MxN. Our study demonstrated the involvement of both RCA, activation energy of Vcmax and stomatal conductance in thermal acclimation of An.

plant biology↗

bioRxiv2018

Examining Academic Leaders work in implementing Competency-based Medical Education (CBME) using Organizational Learning Theory

ContextCompetency-based medical education (CBME) implementation is being carried out in many medical schools worldwide. Academic Leadership is a strategy where selected Faculty act to influence peers to adopt change. The Universite de Montreal medical school, has adopted this strategy to implement CBME.\n\nPurposeThis paper aims to describe the work of Academic Leaders in the process of CBME implementation and to explore relevance of the Nonaka and Toyama organizational learning theory to map implementation progress.\n\nMethodBecause knowledge creation model focuses on the relationships between leaders and social structures, embedded case study was selected. Diverse sampling method was used to select three departments: internal medicine, surgery and psychiatry, based on the number of CBME training activities. Data collection was at two intervals, two years apart. Semi-structured interviews (individual and group) were conducted with Department Heads and Academic Leaders. Thematic analysis was conducted on the 15 interview transcriptions.\n\nResultsAs implementation begins, Leaders critically revisit accepted teaching routines and develop a common conception of CBME. This enables leaders to communicate with a wider audience and work within existing committees and working groups where they \"break down\" CBME into practical concepts. This practical understanding, disseminated through Entrustable Professional Activities, enables observable change.\n\nConclusionLeaders roles evolved from an \"expert\" that disseminates knowledge about CBME through lectures, to a responsive and pragmatic supporting role by developing and writing practical tools in collaboration with peers and program directors.

scientific communication and education↗

bioRxiv2018

Description of cranial elements and ontogenetic change within Tropidolaemus wagleri (Serpentes: Crotalinae)

Tropidolaemus wagleri is a species of Asian pitviper with a geographic range including Thailand, Vietnam, Malaysia, Singapore, Bruniei, parts of Indonesia, and the Philippines. Tropidolaemus is a member of the Crotalinae subfamily, within Viperidae. The genus Tropidolaemus includes five species, and was once included within the genus Trimeresurus. While some osteologic characteristics have been noted a comprehensive description of cranial elements has not been produced for T. wagleri. An in-depth description of the cranial skeleton of Tropidolaemus wagleri lays the foundation for future projects to compare and contrast other taxa within Crotalinae and Viperidae. The chosen reference specimen was compared to the presumed younger specimens to note any variation in ontogeny. The study here provides a comprehensive description of isolated cranial elements as well as a description of ontogenetic change within the specimens observed. This study contributes to the knowledge of osteological characters in T. wagleri and provides a foundation for a long term project to identify isolated elements in the fossil record.

zoology↗

bioRxiv2018

The mitochondrial copper chaperone COX11 plays an auxiliary role in the defence against oxidative stress

COX11, a protein anchored in the inner mitochondrial membrane, was originally identified as a copper chaperone delivering Cu+ to the cytochrome c oxidase of the respiratory chain. Here, we present evidence that this protein is also involved in the defence against reactive oxygen species. Quantitative PCR analyses in the model plant Arabidopsis thaliana revealed that the level of AtCOX11 mRNA rises under oxidative stress. The unexpected result that AtCOX11 knock-down lines contained less ROS than the wild-type can possibly be explained by the impaired oxidative phosphorylation, resulting in less respiration-dependent ROS formation. Similarly, we observed that yeast Saccharomyces cerevisiae ScCOX11 null mutants produced less ROS than wild-type cells. However, when exposed to oxidative stress, yeast strains overexpressing ScCOX11 or AtCOX11 showed lower ROS levels compared with the control indicating a ROS-detoxifying effect of the COX11 proteins. The additive effect on ROS sensitivity upon deletion of ScCOX11 in addition to the known ROS scavenger gene SOD1 encoding superoxide dismutase 1 corroborates the oxidative stress-relieving function of ScCOX11. Moreover, yeast strains overexpressing soluble versions of either AtCOX11 or ScCOX11 became more resistant against oxidative stress. The importance of three conserved cysteines for the ROS scavenger function became apparent after their deletion that resulted in the loss of ROS resistance. Further studies of strains producing COX11 proteins with individually mutated cysteines indicate that the formation of disulphide bridges might be the underlying mechanism responsible for the antioxidative activity of COX11 proteins. Both AtCOX11 and ScCOX11 apparently partake in oxidative stress defence by directly or indirectly exploiting the redox capacity of their cysteine residues.

cell biology↗

bioRxiv2018

Empirical Models for Anatomical and Physiological Changes in a Human Mother and Fetus During Pregnancy and Gestation

Many parameters treated as constants in traditional physiologically based pharmacokinetic models must be formulated as time-varying quantities when modeling pregnancy and gestation due to the dramatic physiological and anatomical changes that occur during this period. While several collections of empirical models for such parameters have been published, each has shortcomings. We sought to create a repository of empirical models for tissue volumes, blood flow rates, and other quantities that undergo substantial changes in a human mother and her fetus during the time between conception and birth, and to address deficiencies with similar, previously published repositories. We used maximum likelihood estimation to calibrate various models for the time-varying quantities of interest, and then used the Akaike information criterion to select an optimal model for each quantity. For quantities of interest for which time-course data were not available, we constructed composite models using percentages and/or models describing related quantities. In this way, we developed a comprehensive collection of formulae describing parameters essential for constructing a PBPK model of a human mother and her fetus throughout the approximately 40 weeks of pregnancy and gestation. We included models describing blood flow rates through various fetal blood routes that have no counterparts in adults. Our repository of mathematical models for anatomical and physiological quantities of interest provides a basis for PBPK models of human pregnancy and gestation, and as such, it can ultimately be used to support decision-making with respect to optimal pharmacological dosing and risk assessment for pregnant women and their developing fetuses. The views expressed in this article are those of the authors and do not necessarily represent the views or policies of the U.S. Environmental Protection Agency.\n\nAUTHOR SUMMARYPhysiologically based pharmacokinetic modeling is a well-known technique for making predictions about internal time-course concentrations of a substance that has entered an organism. This tool is widely used in both pharmaceutical research and human health risk assessment because it harnesses one of the fundamental tenets of both pharmacology and toxicology: it is the concentrations of an active chemical that reach internal target tissues, rather than externally applied \"doses\", that govern the extent of the response (whether beneficial or adverse). Constructing physiologically based pharmacokinetic models for pregnancy and gestation presents a considerable challenge because many of the required parameters (such as blood flow rates or tissue volumes) that are typically assumed to be constant in adult models or short-duration simulations cannot be assumed to be constant when modeling pregnancy. Here we present models, stated as functions of gestational age, for anatomical and physiological changes that occur in a human mother and fetus during pregnancy and gestation. We evaluated and selected models by applying a consistent statistical technique, and where possible, we compared results produced by our models to those produced by previously-published models. The collection of pregnancy parameter models presented here represents the most comprehensive such collection to date.

developmental biology↗

bioRxiv2018

Heterotrimeric G-proteins in unfolded protein response mediate plant growth-defense tradeoffs upstream of steroid and immune signaling

FLAGELLIN-SENSITIVE 2 (FLS2) is a plant immune receptor that binds bacterial flagellin to activate immune signaling. This immune signal is transduced by a heterotrimeric G protein complex at the plasma membrane and activates downstream signaling. However, it is unknown whether the heterotrimeric G proteins have functions at other subcellular locations away from the plasma membrane. Here, we show that components of the heterotrimeric G protein complex stabilize FLS2 protein levels by inhibiting the autophagic degradation of FLS2. Using genetic analysis, we determined that mutations of G protein components resulted in reduced immune signaling in part due to decreased FLS2 protein levels. Furthermore, reduction of FLS2 protein levels was caused by elevated proteasomal and autophagic degradation of FLS2. Genetic inhibition of autophagy in G protein mutants rescued FLS2 levels and immunity. Our findings suggest that the heterotrimeric G protein components, in addition to being part of the heterotrimeric G protein complex that transduces signals at the plasma membrane, also function away from the plasma membrane to control FLS2 protein levels. These results expand the functional capacity of the heterotrimeric G protein complexes in plant immunity.

plant biology↗

bioRxiv2018

SmbHLH37 functions antagonistically with SmMYC2 in regulating jasmonate-mediated biosynthesis of phenolic acids in Salvia miltiorrhiza

Jasmonates (JAs) are integral to various defense responses and induce biosynthesis of many secondary metabolites. MYC2, a basic helix-loop-helix (bHLH) transcription factor (TF), acts as a transcriptional activator of JA signaling. MYC2 is repressed by the JASMONATE ZIM-domain (JAZ) proteins in the absence of JA, but de-repressed by the protein complex SCFCOI1 on perception of JA. We previously reported that overexpression of SmMYC2 promotes the production of salvianolic acid B (Sal B) in Salvia miltiorrhiza. However, the responsible molecular mechanism is unclear. Here, we showed that SmMYC2 binds to and activates the promoters of its target genes SmTAT1, SmPAL1, and SmCYP98A14 to activate Sal B accumulations. SmbHLH37, a novel bHLH gene significantly up-regulated by constitutive expression of SmMYC2, was isolated from S. miltiorrhiza for detailed functional characterization. SmbHLH37 forms a homodimer and interacts with SmJAZ3/8. Overexpression of SmbHLH37 substantially decreased yields of Sal B. SmbHLH37 binds to the promoters of its target genes SmTAT1 and SmPAL1 and blocks their expression to suppress the pathway for Sal B biosynthesis. These results indicate that SmbHLH37 negatively regulates JA signaling and functions antagonistically with SmMYC2 in regulating Sal B biosynthesis in S. miltiorrhiza.

plant biology↗

bioRxiv2018

RegKnock: identifying gene knockout strategies for microbial strain optimization based on regulatory and metabolic integrated network

BackgroundGene knockout has been used to improve the conversion ratio of strains for some chemical products. Based on mixed integer bi-level linear programming (MIBLP) and cell network models, there have been several algorithms to predict the target for deletion to improve the productivity of chemicals. At present, the cell models on which these algorithms based have changed from metabolic network to metabolic-regulatory integrated network, for integrated network is more comprehensive in describing the behavior of cells. Metabolic-regulatory integrated network is better than metabolic network in flux prediction, but will introduce integer variables in the inner of MIBLP. How to solve the intractable MIBLP, however, is not explicated clearly as in mathematical literatures, especially for MIBLP with integer variables in the inner problem (named as MIBLP-2) where integer variables are introduced by the flux balance analysis (FBA) for integrated network. Dual theory was still be used to transform MIBLP-2 to a single level with ignoring integer variables in the inner problem. Intelligent computation is another choice for solving MIBLP, but it usually was used to solve the single level nonlinear programming (NLP) which was the transformation from MIBLP by using joint objective of upper/lower level, while the equivalence between this MIBLP and this NLP was not be proved in mathematics.\n\nMethodsIn this study, we develop a new target predicting algorithm for gene knockouts, named RegKnock. The cell model on which we base is metabolic-regulatory integrated network as well. When solving the MIBLP-2, RegKnock uses Parallel Genetic Algorithm (PGA), but not use joint objective. GA was used to generate control variables of the upper, indicating which genes should be deleted, while the fitness function is to maximize the objective product calculated from the inner FBA of the integrated network. FBA of the inner problem, a mixed integer programming, could be solved by existing optimization softwares. Parallel computation aims to accelerate finding the optimal solution and thus decreases the time of computation.\n\nResults and ConclusionsWith comparing with OptORF and OptFlux, two published target predicting algorithm for gene knockouts which also aiming at integrated network, two merits have been shown for RegKnock, i.e. absolutely accuracy and not a long time of computation. So RegKnock is a nice algorithm for predicting algorithm for gene deletions as for integrated network.

synthetic biology↗

bioRxiv2018

The dynamic proteome of influenza A virus infection identifies M segment splicing as a host range determinant

A century ago, influenza A virus (IAV) infection caused the 1918 flu pandemic and killed an estimated 20-40 million people. Pandemic IAV outbreaks occur when strains from animal reservoirs acquire the ability to infect and spread among humans. The molecular details of this species barrier are incompletely understood. We combined metabolic pulse labeling and quantitative shotgun proteomics to globally monitor protein synthesis upon infection of human cells with a human-and a bird-adapted IAV strain. While production of host proteins was remarkably similar, we observed striking differences in the kinetics of viral protein synthesis over the course of infection. Most importantly, the matrix protein M1 was inefficiently produced by the bird-adapted strain at later stages. We show that impaired production of M1 from bird-adapted strains is caused by increased splicing of the M segment RNA to alternative isoforms. Experiments with reporter constructs and recombinant influenza viruses revealed that strain-specific M segment splicing is controlled by the 3 splice site and functionally important for permissive infection. Independent in silico evidence shows that avian-adapted M segments have evolved different conserved RNA structure features than human-adapted sequences. Thus, our data identifies M segment RNA splicing as a viral determinant of host range.

systems biology↗

bioRxiv2018

Highly mutated memory cells drive an inefficient secondary antibody response to a variant protein

A powerful vaccine against mutable viruses might induce memory antibodies that either strongly bound antigenic variants or that could rapidly undergo secondary affinity maturation to achieve this. We have recently shown after secondary immunization of mice with a widely variant protein (Burton et al. 2018) that IgM+ memory B-cells with few mutations supported an efficient secondary germinal centre (GC) and serum response, superior to a primary response to the same protein. Here, boosting with more closely related proteins produced a GC response dominated by highly mutated B-cells that failed, not efficiently improving serum avidity even in the presence of extra adjuvant, and that was worse than a primary response. This supports a hypothesis that over certain antigenic differences, a cross reactive, mutated, memory B-cell compartment can be an impediment to affinity maturation.

immunology↗

bioRxiv2018

Disease mortality in domesticated animals is predicted by host evolutionary relationships

Infectious diseases of domesticated animals impact human well-being via food insecurity, loss of livelihoods, and human infections. While much research has focused on parasites that infect single host species, most parasites of domesticated mammals infect multiple species. The impact of multi-host parasites varies across hosts; some rarely result in death, whereas others are nearly always fatal. Despite their high ecological and societal costs, we currently lack theory for predicting the lethality of multi-host parasites. Here, using a global dataset of over 4000 case-fatality rates for 65 infectious diseases (caused by micro and macro-parasites) and 12 domesticated host species, we show that the average evolutionary distance from an infected host to other mammal host species is a strong predictor of disease-induced mortality. We find that as parasites infect species outside of their documented phy-1 logenetic host range, they are more likely to result in lethal infections, with the odds of death doubling for each additional 10 million years of evolutionary distance. Our results for domesticated animal diseases reveal patterns in the evolution of highly lethal parasites that are difficult to observe in the wild, and further suggest that the severity of infectious diseases may be predicted from evolutionary relationships among hosts.

evolutionary biology↗

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