Biology subjects

Yang, Z.

Publications and source records attributed to Yang, Z..

At least 343 records · Page 19Linked to original sources

bioRxiv2023

Oligodendroglia generate vascular mural cells and neurons in the adult mouse brain

BACKGROUNDOligodendroglia encompass oligodendrocyte precursor cells (OPCs) and oligodendrocytes (OLs). In the grey matter of the cortex, nearly all OPCs divide slowly, yet they dont differentiate solely into mature OLs, leaving the exact role of these OPCs in the grey matter enigmatic. METHODSOligodendroglia, including OPCs, were traced using the Sox10 Cre-ERT2 reporter mice. We compared the effect of tamoxifen dissolved in different solvents on the fate of Sox10 cells. We also compared the effect of tamoxifen dosage on the fate of Sox10 cells. The differentiation of labeled red fluorescent protein (RFP) cells was analyzed using immunofluorescence staining. RESULTSTwo groups of RFP cells, type A Sox10 (Sox10-A) cells, and type B Sox10 (Sox10-B) cells, were identified in the cortex, striatum, hippocampus, thalamus, and hypothalamus. Sox10-A cells differentiate into platelet-derived growth factor receptor-{beta} (PDGFR{beta})+, CD13+ pericytes, and smooth muscle myosin heavy chain 11 (MYH11) + smooth muscle cells when the mice received ethanol or high-dose tamoxifen. Sox10-B cells transform into glutamatergic neurons when the mice received high-dose tamoxifen. Sox10-B cells include perineurona OPCs and OLs. CONCLUSIONSThis investigation provides evidence that a substantial proportion of oligodendroglia in the grey matter serve as mural cell precursors and neuronal precursors. These two phenomena may contribute to our understanding of neurodegenerative diseases. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=84 SRC="FIGDIR/small/549127v1_ufig1.gif" ALT="Figure 1"> View larger version (14K): org.highwire.dtl.DTLVardef@1b7bef9org.highwire.dtl.DTLVardef@5af54borg.highwire.dtl.DTLVardef@19e3d45org.highwire.dtl.DTLVardef@1c881f1_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Hierarchical heuristic species delimitation under the multispecies coalescent model with migration

The multispecies coalescent (MSC) model accommodates genealogical fluctuations across the genome and provides a natural framework for comparative analysis of genomic sequence data to infer the history of species divergence and gene flow. Given a set of populations, hypotheses of species delimitation (and species phylogeny) may be formulated as instances of MSC models (e.g., MSC for one species versus MSC for two species) and compared using Bayesian model selection. This approach, implemented in the program O_SCPLOWBPPC_SCPLOW, has been found to be prone to over-splitting. Alternatively heuristic criteria based on population parameters under the MSC model (such as population/species divergence times, population sizes, and migration rates) estimated from genomic sequence data may be used to delimit species. Here we extend the approach of species delimitation using the genealogical divergence index (gdi) to develop hierarchical merge and split algorithms for heuristic species delimitation, and implement them in a python pipeline called O_SCPLOWHHSDC_SCPLOW. Applied to data simulated under a model of isolation by distance, the approach was able to recover the correct species delimitation, whereas model comparison by O_SCPLOWBPPC_SCPLOW failed. Analyses of empirical datasets suggest that the procedure may be less prone to over-splitting. We discuss possible strategies for accommodating paraphyletic species in the procedure, as well as the challenges of species delimitation based on heuristic criteria.

bioinformatics↗

bioRxiv2023

Autophagy adaptors mediate Parkin-dependent mitophagy by forming sheet-like liquid condensates

During PINK1 and Parkin-mediated mitophagy, autophagy adaptors are recruited to depolarized mitochondria to promote the selective degradation of mitochondria. Autophagy adaptors such as OPTN and NDP52 bridge mitochondria and autophagosomal membranes by binding to ubiquitinated mitochondrial proteins and autophagosomal ATG8 family proteins. Here, we demonstrate that OPTN and NDP52 form sheet-like phase-separated condensates with liquid-like properties on the surface of ubiquitinated mitochondria. The dynamic and liquid-like feature of OPTN condensates is important for mitophagy activity because reducing the liquidity of OPTN-ubiquitin condensates suppresses the recruitment of ATG9 vesicles and impairs mitophagy. Based on these results, we propose a dynamic liquid-like model of autophagy adaptors, in contrast to a stoichiometric model, to explain their interactions between autophagic membranes (i.e., ATG9 vesicles and isolation membranes) and mitochondrial membranes during Parkin-mediated mitophagy. This model underscores the importance of liquid-liquid phase separation in facilitating membrane- membrane contacts, likely through the generation of capillary forces.

cell biology↗

bioRxiv2023

Converging Topographic Axes of Connectivity and Genetic Architectures Scaffold Cortical Patterning

Genetic information is involved in the gradual emergence of cortical areas since the neural tube begins to form, shaping the heterogeneous functions of neural circuits in the human brain. Informed by invasive tract-tracing measurements, the cortex exhibits marked interareal variation in connectivity profiles to reveal the heterogeneity across cortical areas. However, it remains unclear about the organizing principles possibly shared by genetics and cortical wiring to manifest the spatial heterogeneity across the cortex. Instead of considering a complex one-to-one mapping between genetic coding and interareal connectivity, we hypothesized the existence of a more efficient way that the organizing principles are embedded in genetic profiles to underpin the cortical wiring space. Leveraging on the vertex-wise tractography in diffusion-weighted MRI, we derived the global connectopies to reliably index the organizing principles of interareal connectivity variation in a low-dimensional space, which specifically captured three dominant topographic patterns along the dorsoventral, rostrocaudal, and mediolateral axes of the cortex. More importantly, we demonstrated that the global connectopies converge to the gradients of vertex-by-vertex genetic correlation matrix on the phenotype of cortical morphology and the cortex-wide spatiomolecular gradients. By diving into the genetic profiles, we found the critical role of genes scaffolding the global connectopies were related to brain morphogenesis and enriched in radial glial cells before birth and excitatory neurons after birth. Taken together, our findings demonstrated the existence of a genetically determined space to encode the interareal connectivity variation, which may give new insights into the links between cortical connections and arealization.

neuroscience↗

bioRxiv2023

Hormonal and transcriptomic analysis reveals the role of ABA and BR in breaking the barrier of inter-subgeneric hybridization in water lily (Nymphaea)

Understanding the process of signal communication between pollen and stigma is of significant importance for plant sexual reproduction. In the case of inter-subgeneric hybridization in water lily, there exists a pre-fertilization hybridization barrier, the regulatory mechanism of which remains unclear. In this study, we conducted hormone and transcriptome analyses of unpollinated stigmas (Mock), self-pollinated stigmas (SP), cross-pollinated stigmas within the same subgenus (CP), and inter-subgenus cross-pollination stigmas (ISCP) in water lily to elucidate the formation mechanism of the inter-subgeneric hybridization barrier. Our results indicated that the lack of ABA and BR in ISCP stigmas are key factors contributing to the formation of the inter-subgeneric hybridization barrier in water lily. Exogenous application of ABA and BR can help overcome the barrier between inter-subgeneric water lily crosses. Through transcriptome analysis, we identified nine candidate genes involved in regulating the inter-subgeneric hybridization barrier in water lily. In addition, we further demonstrated the importance of the NCED2-mediated ABA synthesis pathway in the hybridization process through AS-ODN technology. Our study confirms that ABA and BR are critical for breaking the inter-subgeneric hybridization barrier in water lily. The identification of the nine candidate genes provides important clues for further research on the hybridization recognition mechanism in water lily.

plant biology↗

bioRxiv2023

Nifuroxazide enhances radiotherapy efficacy against hepatocellular carcinoma by upregulating PD-L1 degradation via the ubiquitin-proteasome pathway

Radiation therapy is a primary treatment for hepatocellular carcinoma (HCC), but its effectiveness can be diminished by various factors. The over-expression of PD-L1 has been identified as a critical reason for radiotherapy resistance. Previous studies have demonstrated that nifuroxazide exerts antitumor activity by damaging the Stat3 pathway, but its efficacy against PD-L1 has remained unclear. In this study, we investigated whether nifuroxazide could enhance the efficacy of radiotherapy in HCC by reducing PD-L1 expression. Our results showed that nifuroxazide significantly increased the sensitivity of tumor cells to radiation therapy by inhibiting cell proliferation and migration while increasing apoptosis in vitro. Additionally, nifuroxazide attenuated the up-regulation of PD-L1 expression induced by irradiation, which may be associated with increased degradation of PD-L1 through the ubiquitination-proteasome pathway. Furthermore, nifuroxazide greatly enhanced the efficacy of radiation therapy in H22-bearing mice by inhibiting tumor growth, improving survival, boosting the activation of T lymphocytes, and decelerating the ratios of Treg cells in spleens. Importantly, nifuroxazide limited the increased expression of PD-L1 in tumor tissues induced by radiation therapy. This study confirms, for the first time, that nifuroxazide can augment PD-L1 degradation to improve the efficacy of radiation therapy in HCC-bearing mice.

immunology↗

bioRxiv2023

Cucurbituril Enhances Distance Measurements of Spin-Labeled Proteins

We report complex formation between the chloroacetamide 2,6-diazaadamantane nitroxide radical (ClA-DZD) and cucurbit[7]uril (CB-7), for which the association constant in water, Ka = 1.9 x 106 M-1, is at least one order of magnitude higher than the previously studied organic radicals. The radical is highly immobilized by CB-7, as indicated by the increase of the rotational correlation time,{tau} rot, by a factor of 36, relative to that in the buffer solution. The X-ray structure of ClA-DZD@CB-7 shows the encapsulated DZD guest inside the undistorted CB-7 host, with the pendant group protruding outside. Upon addition of CB-7 to T4 Lysozyme (T4L) doubly spin-labeled with the iodoacetamide derivative of DZD, we observe the increase in{tau} rot and electron spin coherence time, Tm, along with the narrowing of inter-spin distance distributions. Sensitivity of the DEER measurements at 83 K increases by a factor 4 - 9, compared to the common spin label such as MTSL, which is not affected by CB-7. Inter-spin distances of 3-nm could be reliably measured in water/glycerol up to temperatures near the glass transition/melting temperature of the matrix at 200 K, thus bringing us closer to the goal of supramolecular recognition-enabled long-distance DEER measurements at near physiological temperatures. The X-ray structure of DZD-T4L 65 at 1.12 [A] resolution allows for unambiguous modeling of the DZD label (0.88 occupancy), indicating undisturbed structure and conformation of the protein. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/554361v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1171bd0org.highwire.dtl.DTLVardef@231612org.highwire.dtl.DTLVardef@17e22e5org.highwire.dtl.DTLVardef@250f1b_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2023

Comparative transcriptome in rhesus macaques and crab-eating macaques

Understanding the variations in gene expression between species is pivotal for deciphering the evolutionary diversity in phenotypes. Rhesus macaques and crab-eating macaques serve as crucial nonhuman primate biomedical models with different phenotypes, but the large-scale of comparative transcriptome research between these two species has yet to be fully elucidated. Here, we conduct systematic comparisons utilizing newly sequenced RNA-seq data from 84 samples encompassing 14 common tissues. Our findings reveal that a small fraction of genes ([~]3.7%) show differential expression between the two macaque species, while [~]36.5% of genes show tissue-specific expression in both macaques. We also compare gene expression between macaques and humans and [~]22.6 % of the orthologous genes show differential expression in at least 2 tissues. Moreover, [~]19.41% of genes overlapped with macaque-specific structural variants are more likely to show differential expression between humans and macaques. Of these, FAM220A shows elevated gene expression in humans compared to macaques because of lineage-specific duplication. In summary, our study presents a large-scale analysis of the transcriptomes within macaque species and between macaques and humans. These insights into gene expression variations will enhance the biomedical utility of macaque models and contributing to the broader realm of primate genomic studies.

bioinformatics↗

bioRxiv2023

Global and local adaptation to aridity in a desert plant Gymnocarpos przewalskii

In order to thrive and survive plant species need to combine stability in the long term and rapid response to environmental challenges in the short term. The former would be reflected by global adaptation across species and the latter by pronounced local adaptation among populations of the same species. It remains unclear how much overlap is to be expected between the parts of the genome associated to these two contrasted adaptation processes. In the present study, we generated a high-quality genome and re-sequenced 177 individuals for Gymnocarpos przewalskii, an important desert plant species from North-West China, to detect local adaptation. To test for global adaptation to aridity at the molecular level we compared genomic data of 15 species that vary in their ability to withstand drought. A total of 118 genes were involved in global adaptation to aridity. Sixty-five G. przewalskii genes were shared across all xerophytic species, of which sixty-three were under stabilizing selection and two under directional selection. While 20% of G. przewalskii genome showed signatures of local adaptation to aridity during population divergence, only 13 of those genes were also under global adaptation. Hence, our results suggest that long-term stability is crucial for adaptation to extreme environmental stress but is only maintained in a small group of highly pleiotropic genes while a rapid response to recent changes elicits a genome-wide response, including gene family expansion. The overlap between the two evolutionary mechanisms appears limited.

evolutionary biology↗

bioRxiv2023

Synergistic activity of rhamnolipid combined with linezolid against linezolid-resistant Enterococcus faecium

Enterococci resistance is increasing sharply, which poses a serious threat to public health. Rhamnolipids are a kind of amphiphilic compound used for its bioactivities, while the combination of nontraditional drugs to restore linezolid activity is an attractive strategy to treat infections caused by these pathogens. This study aimed to investigate the activity of linezolid in combination with the rhamnolipids against Enterococcus faecium. Here, we determined that the rhamnolipids could enhance the efficacy of linezolid against enterococci infections by a checkerboard MIC assay, a time-kill assay, a combined disk test, anti-biofilm assay, molecular simulation dynamics, and mouse infection models. We identified that the combination of rhamnolipids and linezolid restored the linezolid sensitivity. Anti-biofilm experiments show that our new scheme can effectively inhibit biofilm generation. The mouse infection model demonstrated that the combination therapy significantly reduced the bacterial load in the feces, colons and kidneys following subcutaneous administration. This study showed that rhamnolipids could play a synergistic role with linezolid against Enterococcus. Our combined agents could be appealing candidates for developing new combinatorial agents to restore antibiotic efficacy in the treatment of linezolid-resistant Enterococcus infections. HighlightThe identification of a potential inhibitor of LRE, RLS could restore the antibacterial activity of LNZ. A rational mechanism of synergism between LNZ and RLS. ;;L;;RLS in combination with LNZ promote the egress of pathogenic E. faecium from the intestinal tract of mice to reduce its colonization, which has obvious synergistic effects.

microbiology↗

bioRxiv2023

Cell-type-specific plasticity shapes neocortical dynamics for motor learning

Neocortical spiking dynamics control aspects of behavior, yet how these dynamics emerge during motor learning remains elusive. Activity-dependent synaptic plasticity is likely a key mechanism, as it reconfigures network architectures that govern neural dynamics. Here, we examined how the mouse premotor cortex acquires its well-characterized neural dynamics that control movement timing, specifically lick timing. To probe the role of synaptic plasticity, we have genetically manipulated proteins essential for major forms of synaptic plasticity, Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Cofilin, in a region and cell-type-specific manner. Transient inactivation of CaMKII in the premotor cortex blocked learning of new lick timing without affecting the execution of learned action or ongoing spiking activity. Furthermore, among the major glutamatergic neurons in the premotor cortex, CaMKII and Cofilin activity in pyramidal tract (PT) neurons, but not intratelencephalic (IT) neurons, is necessary for learning. High-density electrophysiology in the premotor cortex uncovered that neural dynamics anticipating licks are progressively shaped during learning, which explains the change in lick timing. Such reconfiguration in behaviorally relevant dynamics is impeded by CaMKII manipulation in PT neurons. Altogether, the activity of plasticity-related proteins in PT neurons plays a central role in sculpting neocortical dynamics to learn new behavior.

neuroscience↗

bioRxiv2023

ERK signaling drives evolutionary expansion of the mammalian cerebral cortex

The molecular basis for cortical expansion during evolution remains largely unknown. Here, we found that FGF-extracellular signal-regulated kinase (ERK) signaling promotes the self-renewal and expansion of cortical radial glial (RG) cells. Furthermore, FGF-ERK signaling induces Bmp7 expression in cortical RG cells, which increases the length of the neurogenic period. We demonstrate that ERK signaling and SHH signaling mutually inhibit each other in cortical RG cells. We also provide evidence that ERK signaling is elevated in cortical RG cells during development and evolution. We conclude that the evolutionary expansion of the mammalian cortex, notably in human, is driven by ERK-BMP7-GLI3R signaling pathway in cortical RG cells, which participates in a positive feedback loop through antagonizing SHH signaling. We also propose that the molecular basis for cortical evolutionary dwarfism, exemplified by the lissencephalic mouse which originated from a larger and gyrencephalic ancestor, is due to mouse cortical RG cells receiving higher SHH signaling that antagonizes ERK signaling.

neuroscience↗

bioRxiv2023

Molecular layer disinhibition unlocks climbing-fiber-instructed motor learning in the cerebellum

Climbing fibers supervise cerebellar learning by providing signals to Purkinje cells (PCs) that instruct adaptive changes to mistakenly performed movements. Yet, climbing fibers are regularly active, even during well performed movements, suggesting that a mechanism dynamically regulates the ability of climbing fibers to induce corrective plasticity in response to motor errors. We found that molecular layer interneurons (MLIs), whose inhibition of PCs powerfully opposes climbing-fiber-mediated excitation, serve this function. Optogenetically suppressing the activity of floccular MLIs in mice during the vestibulo-ocular reflex (VOR) induces a learned increase in gain despite the absence of performance errors. Suppressing MLIs when the VOR is mistakenly underperformed reveled that their inhibitory output is necessary to orchestrate gain-increase learning by conditionally permitting climbing fibers to instruct plasticity induction during ipsiversive head turns. Ablation of an MLI circuit for PC disinhibition prevents gain-increase learning during VOR performance errors which was rescued by re-imposing PC disinhibition through MLI activity suppression. Our findings point to a decisive role for MLIs in gating climbing-fiber-mediated learning through their context-dependent inhibition of PCs.

neuroscience↗

bioRxiv2023

Calcium-permeable AMPA receptors govern PV neuron feature selectivity

The brain helps us survive by forming internal representations of the external world1,2. Excitatory cortical neurons are often precisely tuned to specific external stimuli3,4. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective5. PV interneurons differ from excitatory cells in their neurotransmitter receptor subtypes, including AMPA receptors6,7. While excitatory neurons express calcium-impermeable AMPA receptors containing the GluA2 subunit, PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable (CP-AMPARs). Here we demonstrate a causal relationship between CP-AMPAR expression and the low feature selectivity of PV interneurons. We find a low expression stoichiometry of GluA2 mRNA relative to other subunits in PV interneurons which is conserved across ferrets, rodents, marmosets, and humans, causing abundant CP-AMPAR expression. Replacing CP-AMPARs in PV interneurons with calcium-impermeable AMPARs increased their orientation selectivity in the visual cortex. Sparse CP-AMPAR manipulations demonstrated that this increase was cell-autonomous and could occur well beyond development. Interestingly, excitatory-PV interneuron connectivity rates and unitary synaptic strength were unaltered by CP-AMPAR removal, suggesting that the selectivity of PV interneurons can be altered without drastically changing connectivity. In GluA2 knockout mice, where all AMPARs are calcium-permeable, excitatory neurons showed significantly reduced orientation selectivity, suggesting that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type. Remarkably, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, indicating that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality. These results reveal a novel role of CP-AMPARs in maintaining a low-selectivity sensory representation in PV interneurons and suggest a conserved molecular mechanism that distinguishes the unique synaptic computations of inhibitory and excitatory neurons.

neuroscience↗

bioRxiv2023

Hypnotic treatment reverses NREM sleep disruption and EEG desynchronization in a mouse model of Fragile X syndrome to rescue memory consolidation deficits.

Fragile X syndrome (FXS) is a highly-prevalent genetic cause of intellectual disability, associated with disrupted cognition and sleep abnormalities. Sleep loss itself negatively impacts cognitive function, yet the contribution of sleep loss to impaired cognition in FXS is vastly understudied. One untested possibility is that disrupted cognition in FXS is exacerbated by abnormal sleep. We hypothesized that restoration of sleep-dependent mechanisms could improve functions such as memory consolidation in FXS. We examined whether administration of ML297, a hypnotic drug acting on G-protein-activated inward-rectifying potassium channels, could restore sleep phenotypes and improve disrupted memory consolidation in Fmr1-/y mice. Using 24-h polysomnographic recordings, we found that Fmr1-/y mice exhibit reduced non-rapid eye movement (NREM) sleep and fragmented NREM sleep architecture, alterations in NREM EEG spectral power (including reductions in sleep spindles), and reduced EEG coherence between cortical areas. These alterations were reversed in the hours following ML297 administration. Hypnotic treatment following contextual fear or spatial learning also ameliorated disrupted memory consolidation in Fmr1-/y mice. Hippocampal activation patterns during memory recall was altered in Fmr1-/y mice, reflecting an altered balance of activity among principal neurons vs. parvalbumin-expressing (PV+) interneurons. This phenotype was partially reversed by post-learning ML297 administration. These studies suggest that sleep disruption could have a major impact on neurophysiological and behavioral phenotypes in FXS, and that hypnotic therapy may significantly improve disrupted cognition in this disorder.

neuroscience↗

bioRxiv2023

Interaction between host G3BP and viral nucleocapsid protein regulates SARS-CoV-2 replication

G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. G3BP1/2 are prominent interactors of the nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the functional consequences of the G3BP1-N interaction in the context of viral infection remain unclear. Here we used structural and biochemical analyses to define the residues required for G3BP1-N interaction, followed by structure-guided mutagenesis of G3BP1 and N to selectively and reciprocally disrupt their interaction. We found that mutation of F17 within the N protein led to selective loss of interaction with G3BP1 and consequent failure of the N protein to disrupt stress granule assembly. Introduction of SARS-CoV-2 bearing an F17A mutation resulted in a significant decrease in viral replication and pathogenesis in vivo, indicating that the G3BP1-N interaction promotes infection by suppressing the ability of G3BP1 to form stress granules.

cell biology↗

bioRxiv2023

Polygenic risk score prediction accuracy convergence

Polygenic risk scores (PRS) trained from genome-wide association study (GWAS) results are set to play a pivotal role in biomedical research addressing multifactorial human diseases. The prospect of using these risk scores in clinical care and public health is generating both enthusiasm and controversy, with varying opinions about strengths and limitations across experts1. The performances of existing polygenic scores are still limited, and although it is expected to improve with increasing sample size of GWAS and the development of new powerful methods, it remains unclear how much prediction can be ultimately achieved. Here, we conducted a retrospective analysis to assess the progress in PRS prediction accuracy since the publication of the first large-scale GWASs using six common human diseases with sufficient GWAS data. We show that while PRS accuracy has grown rapidly for years, the improvement pace from recent GWAS has decreased substantially, suggesting that further increasing GWAS sample size may translate into very modest risk discrimination improvement. We next investigated the factors influencing the maximum achievable prediction using recently released whole genome-sequencing data from 125K UK Biobank participants, and state-of-the-art modeling of polygenic outcomes. Our analyses point toward increasing the variant coverage of PRS, using either more imputed variants or sequencing data, as a key component for future improvement in prediction accuracy.

genetics↗

bioRxiv2023

Major patterns in the introgression history of Heliconius butterflies

AO_SCPLOWBSTRACTC_SCPLOWGene flow between species is an important evolutionary process that can facilitate adaptation and lead to species diversification. It also makes reconstruction of species relationships difficult. Here, we use the full-likelihood multispecies coalescent (MSC) approach to estimate species phylogeny and major introgression events in Heliconius butterflies from whole-genome sequence data. We obtain a robust estimate of species branching order among major clades in the genus, including the "melpomene-silvaniform" group, which shows extensive historical and on-going gene flow. We obtain chromosome-level estimates of key parameters in the species phylogeny, including species divergence times, present-day and ancestral population sizes as well as the direction, timing, and intensity of gene flow. Our analysis leads to a phylogeny with introgression events that differ from those obtained in previous studies. We find that H. aoede most likely represents the earliest-branching lineage of the genus and that "silvaniform" species are paraphyletic within the melpomene-silvaniform group. Our phylogeny provides new, parsimonious histories for the origins of key traits in Heliconius, including pollen feeding and an inversion involved in wing pattern mimicry. Our results demonstrate the power and feasibility of the full-likelihood MSC approach for estimating species phylogeny and key population parameters despite extensive gene flow. The methods used here should be useful for analysis of other difficult species groups with high rates of introgression.

evolutionary biology↗