Biology subjects

Kang, M.

Publications and source records attributed to Kang, M..

89 records · Page 5Linked to original sources

bioRxiv2020

Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells

Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation. This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/ One sentence summarySARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19.

immunology↗

bioRxiv2020

Rapid tolerance to morphine in the myenteric neurons of the small intestine is independent of β-arrestin-2

Background and PurposeG-protein biased -opioid agonists against {beta}-arrestin-2 activation are being investigated to reduce adverse effects. While opioid tolerance is strongly linked to the development of dependence, there is a dissociation between the two phenomena in the gut as tolerance does not develop to opioid-induced constipation, but diarrhea still manifests upon withdrawal. Here, we investigated the mechanism by which morphine tolerance in the small intestine develops. Experimental ApproachMechanism of morphine tolerance in the small intestine was evaluated in vivo and at the neuronal level. Whole-cell patch clamp electrophysiology was used to investigate tolerance in individual ileum myenteric neurons. Rate of morphine tolerance development in the small intestine was assessed against peripheral antinociception and whole gut transit. Key ResultsTolerance develops to inhibition of small intestinal motility after one day of morphine exposure, and is more rapid compared to peripheral antinociception and constipation in chronic morphine-treated mice. Morphine tolerance was reversed by the PKC inhibitor, Tamoxifen, but not by {beta}-arrestin-2 deletion. Similarly, {beta}-arrestin-2 deletion did not prevent morphine tolerance to inhibition of neuronal excitability in ileum myenteric neurons. However, neuronal tolerance was attenuated by inhibiting PKC. Conclusions and ImplicationsUnlike antinociceptive tolerance, rapid morphine tolerance in the small intestine is independent of {beta}-arrestin-2 but is PKC-mediated. These findings reveal a potential mechanism for differences in the rates of tolerances to opioids, implicate myenteric neurons of the ileum as the primary cause for opioid-induced withdrawal effects and suggest that undesired gastrointestinal effects will persist with biased opioid agonist use. SummaryWhat is already known: O_LITolerance does not develop to chronic-opioid-induced constipation but diarrhea is produced upon withdrawal C_LIO_LINovel G-protein biased agonists that preclude {beta}-arrestin-2 activation at the -opioid receptor are in development C_LI What this study adds: O_LIMorphine tolerance in the ileum develops systemically and in individual myenteric neurons independent of {beta}-arrestin-2 C_LIO_LIMorphine tolerance in the small intestine develops before antinociception and is reversed by PKC inhibition C_LI Clinical significance: O_LIClinical use of G-protein biased opioid agonists will not prevent tolerance development in the ileum C_LIO_LITolerance in ileum myenteric neurons might be the basis of opioid-induced withdrawal in the gut C_LI

pharmacology and toxicology↗

bioRxiv2020

A self-initiated cue-reward learning procedure for neural recording in rodents

BackgroundSingle-unit recording in Pavlovian conditioning tasks requires the use of within-subject designs as well as sampling a considerable number of trials per trial type and session, which increases the total trial count. Pavlovian conditioning, on the other hand, requires a long average intertrial interval (ITI) relative to cue duration for cue-specific learning to occur. These requirements combined can make the session duration unfeasibly long. New MethodTo circumvent this issue, we developed a self-initiated variant of the Pavlovian magazine-approach procedure in rodents. Unlike the standard procedure, where the animals passively receive the trials, the self-initiated procedure grants animals agency to self-administer and self-pace trials from a predetermined, pseudorandomized list. Critically, whereas in the standard procedure the typical ITI is in the order of minutes, our procedure uses a much shorter ITI (10 s). ResultsDespite such a short ITI, discrimination learning in the self-initiated procedure is comparable to that observed in the standard procedure with a typical ITI, and superior to that observed in the standard procedure with an equally short ITI. Comparison with Existing Method(s)The self-initiated procedure permits delivering 100 trials in a [~]1-h session, almost doubling the number of trials safely attainable over that period with the standard procedure. ConclusionsThe self-initiated procedure enhances the collection of neural correlates of cue-reward learning while producing good discrimination performance. Other advantages for neural recording studies include ensuring that at the start of each trial the animal is engaged, attentive and in the same location within the conditioning chamber.

neuroscience↗

bioRxiv2020

Differential TM4SF5-mediated SIRT1 modulation and signaling for chronic liver disease

Here we show the roles of transmembrane 4 L six family member 5 (TM4SF5) in the progression of nonalcoholic steatosis (or NAFL) to steatohepatitis (NASH). The overexpression of TM4SF5 caused nonalcoholic steatosis and NASH in an age-dependent manner. Initially, TM4SF5-positive hepatocytes and livers exhibited lipid accumulation, decreased SIRT1, increased SREBPs levels, and inactive STAT3 via SOCS1/3 upregulation. In older animals, TM4SF5 under an inflammatory environment increased SIRT1 expression and STAT3 activity with no significant change to SOCSs and SREBPs levels, leading to active STAT3-mediated fibrotic extracellular matrix (ECM) production. Liver tissues from clinical human patients with NAFL or NASH also showed such a TM4SF5-SIRT1-STAT3-ECM relationship correlated with fibrosis score and age. Ligand-independent and TM4SF5-mediated STAT3 activity led to collagen I and laminins/laminin {gamma}2 expression in hepatic stellate cells and hepatocytes, respectively. Laminin {gamma}2 suppression abolished CCl4-mediated liver damage and ECM production and reduced SIRT1 and active-STAT3, but did not alter SREBP1 or SOCSs levels. These findings suggest that TM4SF5, CCL20, SIRT1, and/or laminin {gamma}2 may be promising therapeutic targets against liver disease.

cell biology↗

bioRxiv2020

Transmission dynamics of 2019 novel coronavirus (2019-nCoV)

RationaleSeveral studies have estimated basic production number of novel coronavirus pneumonia (NCP). However, the time-varying transmission dynamics of NCP during the outbreak remain unclear. ObjectivesWe aimed to estimate the basic and time-varying transmission dynamics of NCP across China, and compared them with SARS. MethodsData on NCP cases by February 7, 2020 were collected from epidemiological investigations or official websites. Data on severe acute respiratory syndrome (SARS) cases in Guangdong Province, Beijing and Hong Kong during 2002-2003 were also obtained. We estimated the doubling time, basic reproduction number (R0) and time-varying reproduction number (Rt) of NCP and SARS. Measurements and main resultsAs of February 7, 2020, 34,598 NCP cases were identified in China, and daily confirmed cases decreased after February 4. The doubling time of NCP nationwide was 2.4 days which was shorter than that of SARS in Guangdong (14.3 days), Hong Kong (5.7 days) and Beijing (12.4 days). The R0 of NCP cases nationwide and in Wuhan were 4.5 and 4.4 respectively, which were higher than R0 of SARS in Guangdong (R0=2.3), Hongkong (R0=2.3), and Beijing (R0=2.6). The Rt for NCP continuously decreased especially after January 16 nationwide and in Wuhan. The R0 for secondary NCP cases in Guangdong was 0.6, and the Rt values were less than 1 during the epidemic. ConclusionsNCP may have a higher transmissibility than SARS, and the efforts of containing the outbreak are effective. However, the efforts are needed to persist in for reducing time-varying reproduction number below one. At a Glance CommentaryO_ST_ABSScientific Knowledge on the SubjectC_ST_ABSSince December 29, 2019, pneumonia infection with 2019-nCoV, now named as Novel Coronavirus Pneumonia (NCP), occurred in Wuhan, Hubei Province, China. The disease has rapidly spread from Wuhan to other areas. As a novel virus, the time-varying transmission dynamics of NCP remain unclear, and it is also important to compare it with SARS. What This Study Adds to the FieldWe compared the transmission dynamics of NCP with SARS, and found that NCP has a higher transmissibility than SARS. Time-varying production number indicates that rigorous control measures taken by governments are effective across China, and persistent efforts are needed to be taken for reducing instantaneous reproduction number below one.

systems biology↗

bioRxiv2019

Fitness Functions Determine Optimal Parental Allocation: Redefining Trivers Willard Theory

According to Trivers-Willard theory1, females in a good condition should carry more male offspring to maximize their fitness while should carry more females in a poor condition. Diverse theoretical and empirical studies has been performed to verify the validity of this claim2,3. Some portion of the empirical observations, however, exhibited contrary outcome to Trivers-Willard theory4. To resolve this problem, we computationally and mathematically show in here that reversed Trivers-Willard theory actually could be the outcome of the parental fitness optimization. In our models with identical fitness functions, we found that selective equitable care is optimal, and the number of the cared offspring should monotonically increase with maternal condition (or expendable parental investment). In some of our models with two distinguished male and female fitness functions, optimizations results were congruent with the conventional Trivers-Willard theory. In other models of ours, contrary to Trivers-Willard theory, it was optimal to invest in males when maternal condition was low. The results along with our hypothesis can explain the empirical observations that were previously thought to be the counterexample of Trivers-Willard theory. We propose that Trivers-Willard theory should be interpreted in multidimensional way, and more elaborate empirical data need to be collected to verify such propositions.

evolutionary biology↗

bioRxiv2019

The apparent requirement for protein synthesis during G2 phase is due to checkpoint activation

Protein synthesis inhibitors (e.g. cycloheximide) prevent cells from entering mitosis, suggesting that cell cycle progression requires protein synthesis until right before mitotic entry. However, cycloheximide is also known to activate p38 MAPK, which can delay mitotic entry through a G2/M checkpoint. Here we asked whether checkpoint activation or a requirement for protein synthesis is responsible for the cycloheximide effect. We found that p38 inhibitors prevent cycloheximide-treated cells from arresting in G2 phase, and that G2 duration is normal in about half of these cells. The Wee1/Myt1 inhibitor PD0166285 also prevents cycloheximide from blocking mitotic entry, raising the possibility that Wee1 and/or Myt1 mediate the cycloheximide-induced G2 arrest. Thus, the ultimate trigger for mitotic entry appears not to be the continued synthesis of mitotic cyclins or other proteins. However, M-phase progression was delayed in cycloheximide-plus-kinase-inhibitor-treated cells, emphasizing the different requirements of protein synthesis for timely entry and completion of mitosis. Impact statementCycloheximide arrests cells in G2 phase due to activation of p38 MAPK, not inhibition of protein synthesis, arguing that protein synthesis in G2 phase is not required for mitotic entry.

cell biology↗

bioRxiv2019

Molecular mechanisms behind global distribution of earthworm revealed by the genome

Earthworms (Annelida: Crassiclitellata), are widely distributed around the world due to their great adaptability. However, lack of a high-quality genome sequence prevents gaining the many insights into physiology, phylogeny, and genome evolution that could come from a good earthworm genome. Herein, we report a complete genome assembly of the earthworm Amynthas corticis of about 1.2 Gb, based on a strategy combining third-generation long-read sequencing and Hi-C mapping. A total of 29,256 protein-coding genes are annotated in this genome. Analysis of resequencing data indicates that this earthworm is a triploid species. Furthermore, gene family evolution analysis shows that comprehensive expansion of gene families in the earthworm genome has produced more defensive functions compared with other species in Annelida. Quantitative proteomic iTRAQ analysis shows 97 immune related proteins and 16S rDNA sequences shows 88 microbes with significantly response to pathogenic Escherichia coli O157:H7. Our genome assembly provides abundant and valuable resources for the earthworm research community, serving as a first step toward uncovering the mysteries of this species, may explain its powerful defensive functions adapt to complex environment and invasion from molecular level.

genomics↗

bioRxiv2019

Structural and molecular insight into the pH-induced low-permeability of the voltage-gated potassium channel Kv1.2 through dewetting of the water cavity

Understanding the gating mechanism of ion channel proteins is key to understanding the regulation of cell signaling through these channels. Channel opening and closing are regulated by diverse environmental factors that include temperature, electrical voltage across the channel, and proton concentration. Low permeability in voltage-gated potassium ion channels (Kv) is intimately correlated with the prolonged action potential duration observed in many acidosis diseases. The Kv channels consist of voltage-sensing domains (S1-S4 helices) and central pore domains (S5-S6 helices) that include a selectivity filter and water-filled cavity. The voltage-sensing domain is responsible for the voltage-gating of Kv channels. While the low permeability of Kv channels to potassium ion is highly correlated with the cellular proton concentration, it is unclear how an intracellular acidic condition drives their closure, which may indicate an additional pH-dependent gating mechanism of the Kv family. Here, we show that two residues E327 and H418 in the proximity of the water cavity of Kv1.2 play crucial roles as a pH switch. In addition, we present a structural and molecular concept of the pH-dependent gating of Kv1.2 in atomic detail, showing that the protonation of E327 and H418 disrupts the electrostatic balance around the S6 helices, which leads to a straightening transition in the shape of their axes and causes dewetting of the water-filled cavity and closure of the channel. Our work offers a conceptual advancement to the regulation of the pH-dependent gating of various voltage-gated ion channels and their related biological functions.\n\nAuthor SummaryThe acid sensing ion channels are a biological machinery for maintaining the cell functional under the acidic or basic cellular environment. Understanding the pH-dependent gating mechanism of such channels provides the structural insight to design the molecular strategy in regulating the acidosis. Here, we studied the voltage-gated potassium ion channel Kv1.2 which senses not only the electrical voltage across the channels but also the cellular acidity. We uncovered that two key residues E327 and H418 in the pore domain of Kv1.2 channel play a role as pH-switch in that their protonation control the gating of the pore in Kv1.2 channel. It offered a molecular insight how the acidity reduces the ion permeability in voltage-gated potassium channels.

biophysics↗

bioRxiv2019

IL-1RA controls the development of esophageal cancer by inhibition of VEGF via PI3K/NF-κB signaling pathway

IL-1RA has been reported to function as tumor suppressor in a variety of tumors, but its function and mechanism in esophageal cancer remains largely unknown. Our previous studies have shown that IL-1RA is downregulated in primary esophageal cancer(EC), and this downregulation of IL-1RA is closely related to TNM staging and survival prognosis. In this study, we observed that over-expression of IL-1RA inhibits proliferation, migration, and tumor growth in esophageal cancer cells(ESCC), inhibits the expression and secretion of VEGF, and inhibits tumor angiogenesis. Further studies have shown the overexpression of IL-1RA inhibits the transmission of PI3K/NF-kappaB. Taken together, this study shows that IL-1RA can regulating the development of esophageal cancer by inhibiting VEGF expression and secretion via inhibiting PI3K/NF-kappaB signaling, and it may serve as a potential prognostic marker and therapeutic target for EC.

cancer biology↗

bioRxiv2019

Rapid and label-free identification of individual bacterial pathogens exploiting three-dimensional quantitative phase imaging and deep learning

The healthcare industry is in dire need for rapid microbial identification techniques. Microbial infection is a major healthcare issue with significant prevalence and mortality, which can be treated effectively during the early stages using appropriate antibiotics. However, determining the appropriate antibiotics for the treatment of the early stages of infection remains a challenge, mainly due to the lack of rapid microbial identification techniques. Conventional culture-based identification and matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy are the gold standard methods, but the sample amplification process is extremely time-consuming. Here, we propose an identification framework that can be used to measure minute quantities of microbes by incorporating artificial neural networks with three-dimensional quantitative phase imaging. We aimed to accurately identify the species of bacterial bloodstream infection pathogens based on a single colony-forming unit of the bacteria. The successful distinction between a total of 19 species, with the accuracy of 99.9% when ten bacteria were measured, suggests that our framework can serve as an effective advisory tool for clinicians during the initial antibiotic prescription. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/596486v2_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@786668org.highwire.dtl.DTLVardef@8b4eb4org.highwire.dtl.DTLVardef@1dc2452org.highwire.dtl.DTLVardef@1d4888c_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2019

Mitotic gene bookmarking by RUNX1 contributes to stabilization of the normal mammary epithelial phenotype

RUNX1 has recently been shown to play an important role in determination of mammary epithelial cell identity. However, mechanisms by which loss of the RUNX1 transcription factor in mammary epithelial cells leads to epithelial-to-mesenchymal transition (EMT) are not known. Here, we report mitotic bookmarking of genes by RUNX1 as a potential mechanism to convey regulatory information through successive cell divisions for coordinate control of mammary cell proliferation, growth, and identity. Genome-wide RUNX1 occupancy profiles for asynchronous, mitotically enriched, and early G1 breast epithelial cells reveal RUNX1 is retained during the mitosis to G1 transition on protein coding and long non-coding RNA genes critical for mammary epithelial proliferation, growth, and phenotype maintenance. Disruption of RUNX1 DNA binding and association with mitotic chromosomes alters cell morphology, global protein synthesis, and phenotype-related gene expression. Together, these findings show for the first time that RUNX1 bookmarks a subset of epithelial-related genes during mitosis that remain occupied as cells enter the next cell cycle. Compromising RUNX1 DNA binding initiates EMT, an essential first step in the onset of breast cancer. SignificanceThis study elucidates mitotic gene bookmarking as a potential epigenetic mechanism that impacts breast epithelial cell growth and phenotype and has potential implications in breast cancer onset.

cancer biology↗

bioRxiv2018

Transitions in cell potency during early mouse development are driven by Notch

The Notch signalling pathway plays fundamental roles in diverse developmental processes in metazoans, where it is important in driving cell fate and directing differentiation of various cell types. However, we still have limited knowledge about the role of Notch in early preimplantation stages of mammalian development, or how it interacts with other signalling pathways active at these stages such as Hippo. By using genetic and pharmacological tools in vivo, together with image analysis of single embryos and pluripotent cell culture, we have found that Notch is active from the 4-cell stage. Transcriptomic analysis in single morula identified novel Notch targets, such as early naive pluripotency markers or transcriptional repressors such as TLE4. Our results reveal a previously undescribed role for Notch in driving transitions during the gradual loss of potency that takes place in the early mouse embryo prior to the first lineage decisions.

developmental biology↗

bioRxiv2018

Joint single cell DNA-Seq and RNA-Seq of gastric cancer reveals subclonal signatures of genomic instability and gene expression

Sequencing the genomes of individual cancer cells provides the highest resolution of intratumoral heterogeneity. To enable high throughput single cell DNA-Seq across thousands of individual cells per sample, we developed a droplet-based, automated partitioning technology for whole genome sequencing. We applied this approach on a set of gastric cancer cell lines and a primary gastric tumor. In parallel, we conducted a separate single cell RNA-Seq analysis on these same cancers and used copy number to compare results. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection - where the percentage of replicating cells per clone is higher than expected - indicating ongoing tumor evolution. Our study demonstrates that joining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology. SIGNIFICANCEWe conducted a massively parallel DNA sequencing analysis on a set of gastric cancer cell lines and a primary gastric tumor in combination with a joint single cell RNA-Seq analysis. This joint study, covering thousands of single cell genomes and transcriptomes, revealed extensive cellular diversity based on distinct copy number changes, numerous subclonal populations and in the case of the primary tumor, subclonal gene expression signatures. We found genomic evidence of positive selection where the percentage of replicating cells per clone is higher than expected indicating ongoing tumor evolution. Our study demonstrates that combining single cell genomic DNA and transcriptomic features provides novel insights into cancer heterogeneity and biology.

genomics↗

bioRxiv2017

Development of cross-orientation suppression and size tuning and the role of experience

Many sensory neural circuits exhibit response normalization, which occurs when the response of a neuron to a combination of multiple stimuli is less than the sum of the responses to the individual stimuli presented alone. In the visual cortex, normalization takes the forms of cross-orientation suppression and surround suppression. At the onset of visual experience, visual circuits are partially developed and exhibit some mature features such as orientation selectivity, but it is unknown whether cross-orientation suppression or surround suppression are present at the onset of visual experience or require visual experience for their emergence. We characterized the development of these properties and their dependence on visual experience in ferrets. Visual experience was varied across three conditions: typical rearing, dark rearing, and dark rearing with daily exposure to simple sinusoidal gratings (14-16 hours total). Cross-orientation suppression and surround suppression were noted in the earliest observations, and did not vary considerably with experience. We also observed evidence of continued maturation of receptive field properties in the second month of visual experience: substantial length summation was observed only in the oldest animals (postnatal day 90); evoked firing rates were greatly increased in older animals; and direction selectivity required experience, but declined slightly in older animals. These results constrain the space of possible circuit implementations of these features.\n\nSignificance StatementThe development of the brain depends on both nature - factors that are independent of the experience of an individual animal - and nurture - factors that depend on experience. While orientation selectivity, one of the major response properties of neurons in visual cortex, is already present at the onset of visual experience, it is unknown if response properties that depend on interactions among multiple stimuli develop without experience. We find that the properties of crossorientation suppression and surround suppression are present at eye opening, and do not depend on visual experience. Our results are consistent with the idea that a majority of the basic properties of sensory neurons in primary visual cortex are derived independent of the experience of an individual animal.

neuroscience↗

bioRxiv2017

Functional characterization of the ABF gene family in upland cotton (Gossypium hirsutum L.)

The AREB/ABF bZIP transcription factors play a pivotal role in abscisic acid-dependent abiotic stress-responsive gene expression. Despite the perennial damage and reduced productivity that result from water-deficit and unpredictable early season temperature fluctuations, these critical genes have not been previously examined in upland cotton (Gossypium hirsutum). Here, we report the isolation of the G. hirsutum ABF homologs, characterization of their expression patterns in response to abiotic stress treatments, and examination of their functions through heterologous ectopic expression in Arabidopsis. As expected for an allotetraploid, G. hirsutum ABF homologs are present in the genome as homeologous pairs. These genes are differentially expressed, both among the homologs and within the homeologous pairs, in response to exogenous abscisic acid (ABA) application, dehydration, and chilling temperatures. Furthermore, heterologous ectopic expression of many of the G. hirsutum ABF genes in Arabidopsis conferred increased tolerance to water deficit and osmotic stress, as well as cold tolerance, in a gene specific manner. These results indicate the G. hirsutum ABF homologs are functional in Arabidopsis and, as in other species, are likely to play an essential role in the abiotic stress response.\n\nHighlightThe Gossypium hirsutum ABF homeologs are differentially expressed in response to abiotic stress, and their ectopic expression in Arabidopsis can confer increased water deficit tolerance.

plant biology↗

bioRxiv2017

Molecular evolution, diversity and adaptation of H7N9 influenza A viruses in China

A novel H7N9 avian influenza virus has caused five human epidemics in China since 2013. The substantial increase in prevalence and the emergence of antigenically divergent or highly pathogenic (HP) H7N9 strains during the current outbreak raises concerns about the epizootic-potential of these viruses. Here, we investigate the evolution and adaptation of H7N9 by combining publicly available data with newly generated virus sequences isolated in Guangdong between 2015-2017. Phylogenetic analyses show that currently-circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Using ancestral sequence reconstruction and structural modelling we have identified parallel amino-acid changes on multiple separate lineages. Furthermore, we infer mutations in HA primarily occur at sites involved in receptor-recognition and/or antigenicity. We also identify seven new HP strains, which likely emerged from viruses circulating in eastern Guangdong around March 2016 and is further associated with a high rate of adaptive molecular evolution.

evolutionary biology↗