Biology subjects

Musser, J. M.

Publications and source records attributed to Musser, J. M..

At least 19 recordsLinked to original sources

bioRxiv2026

From promiscuity to specialization: The origin of cholinergic and monoaminergic signaling is pre-bilaterian

The emergence of chemical neurotransmission was key to the evolution of nervous systems, yet when the different transmitter systems arose remains unclear. Biogenic amines (here, acetylcholine and the monoamines) have been reported in non-bilaterian animals and even outside Metazoa, but their physiological role has only recently begun to be resolved, and phylogenetic surveys of the bilaterian machinery have restricted dedicated monoaminergic signaling to Bilateria. Combining targeted metabolomics, molecular phylogenies, structural modeling and binding-affinity prediction, single-cell expression analysis and immunochemistry, we show that cholinergic and monoaminergic signaling predate Bilateria. We detect acetylcholine, dopamine, histamine, adrenaline, tyramine, 2-phenylethylamine and tryptamine in a sponge and two cnidarians, and identify broad-specificity enzymes and transporters able to produce and load them. These genes are co-expressed in both neuronal and non-neuronal cell types, indicating that amine signaling was never confined to the nervous system. Two Hydra vulgaris muscarinic receptor orthologs retain a fully conserved orthosteric site and are predicted to bind acetylcholine as strongly as their bilaterian counterparts, and muscle-type nicotinic receptor subunits are co-expressed with Rapsyn-related genes in cnidarian muscle cells, placing cholinergic neuromuscular signaling in the cnidarian-bilaterian ancestor. Specialization came later in Bilateria, where gene duplications produced substrate-specific enzymes (ChAT, TH, TPH), dedicated vesicular transporters (VAChT, VMAT) and ligand-selective receptors. Biogenic amine signaling is thus not a bilaterian innovation but an ancient mode of cellular communication that evolved from generalist to specialist machinery.

evolutionary biology↗

bioRxiv2026

An ancient monoaminergic signaling system coordinates contractility in a nerveless sponge

Chemical neurotransmission was a key animal innovation, enabling multicellular coordination of physiology and locomotion. Sponges are early-diverging animals that lack neurons and muscles, yet still coordinate contraction and relaxation of their filter-feeding water canals. Here, we show that Spongilla lacustris synthesizes the monoamines tryptamine, phenethylamine, and tyramine to elicit distinct canal behaviors. We identify previously uncharacterized decarboxylases and vesicular transporters coexpressed in secretory neuroid and metabolic cells. Using phosphoproteomics and label-free 3D imaging, we show that tryptamine activates GPCR signaling and Rho GTPases, remodeling adhesion and actomyosin networks in contractile canal epithelia to drive localized constrictions and whole-body deflations. Together, these findings define an ancestral monoaminergic system linking secretory and contractile cell types that predate neurons and was later elaborated for neuromodulation of synaptic transmission.

evolutionary biology↗

bioRxiv2026

Gene contribution of Streptococcus dysgalactiae subspecies equisimilis, an emerging pathogen, to experimental primate necrotizing myositis

Streptococcus dysgalactiae subspecies equisimilis (SDSE) is an emerging human pathogen closely related to group A streptococcus. However, its genetic requirements for survival and growth in different conditions and for causing invasive infections remain poorly understood. To address this gap, we used Transposon-Directed Insertion-site Sequencing (TraDIS) to identify genes contributing to fitness in experimental necrotizing myositis in non-human primates (NHPs). Using two SDSE stG62647 human clinical isolates, MGCS36044 and MGCS36089, we generated highly saturated transposon mutant libraries and analyzed them following in vitro growth and in vivo infection in eight NHPs. We identified 398 essential genes shared by both strains during growth in vitro and in vivo, and 17 and seven conditionally essential genes required only in vitro or only in vivo, respectively. Additionally, we identified 117 and 110 genes in MGCS36044 and MGCS36089, respectively, that were associated with fitness during necrotizing myositis. Transposon insertions in 34 MGCS36044 genes conferred increased fitness, whereas mutation of 83 genes conferred decreased fitness. Similarly, in MGCS36089, mutations in 38 and 72 genes conferred increased or decreased fitness, respectively. Importantly, both strains shared 46 fitness-associated genes, including an enrichment of transporter genes, highlighting nutrient acquisition as a dominant requirement during infection. The results provide critical information for guiding future translational efforts to develop preventive and therapeutic strategies against human SDSE infections.

microbiology↗

bioRxiv2025

Intra-host genomic variation of Haemophilus influenzae isolates from asymptomatic nasopharyngeal carriers involves genes encoding proteins with diverse inferred functions

Haemophilus influenzae is a human-specific pathogen that causes infections ranging in severity from otitis media to potentially fatal meningitis. It also asymptomatically colonizes the upper respiratory tract. Although intra-host genomic variation of H. influenzae has been investigated in some anatomic sites, the genes most frequently acquiring nonsynonymous (amino acid changing) or nonsense (protein truncating) single nucleotide polymorphisms (SNPs) during human carriage or infection remain largely unidentified. To study intra-host genomic variation of H. influenzae during human asymptomatic carriage in the nasopharynx, the genomes of 805 isolates recovered from 24 healthy Icelandic children were sequenced. Most children were colonized with isolates with a single multilocus sequence type (MLST), although some were concurrently colonized with isolates with multiple MLSTs. Intra-host genomic variation was discovered with 120 genes acquiring SNPs in at least one isolate. Among them, 69 genes were recurrently polymorphic in isolates recovered from multiple children, and 72 SNPs occurred in multiple isolates recovered from the same child. The polymorphic genes encode proteins with diverse inferred functions, including transcription regulators and putative virulence factors. Many of the proteins likely play roles in bacterial fitness, virulence, and host-pathogen molecular interactions. This intra-host variation study provides a model for understanding the genomic diversity acquired by H. influenzae during human asymptomatic carriage in the nasopharynx.

microbiology↗

bioRxiv2024

sc-SPLASH provides ultra-efficient reference-free discovery in barcoded single-cell sequencing

Typical high-throughput single-cell RNA-sequencing (scRNA-seq) analyses are primarily conducted by (pseudo)alignment, through the lens of annotated gene models, and aimed at detecting differential gene expression. This misses diversity generated by other mechanisms that diversify the transcriptome such as splicing and V(D)J recombination, and is blind to sequences missing from imperfect reference genomes. Here, we present sc-SPLASH, a highly efficient pipeline that extends our SPLASH framework for statistics-first, reference-free discovery to barcoded scRNA-seq (10x Chromium) and spatial transcriptomics (10x Visium); we also provide its optimized module for preprocessing and k-mer counting in barcoded data, BKC, as a standalone tool. sc-SPLASH rediscovers known biology including V(D)J recombination and cell-type-specific alternative splicing in human and trans-splicing in tunicate (Ciona) and when applied to spatial datasets, detects sequence variation including tumor-specific somatic mutation. In sponge (Spongilla) and tunicate (Ciona), we uncover secreted repeat proteins expressed in immune-type cells and regulated during development; the sponge genes were absent from the reference assembly. sc-SPLASH provides a powerful alternative tool for exploring transcriptomes that is applicable to the breadth of lifes diversity.

bioinformatics↗

bioRxiv2023

Molecular profiling of sponge deflation reveals an ancient relaxant-inflammatory response

A hallmark of animals is the coordination of whole-body movement. Neurons and muscles are central to this, yet coordinated movements also exist in sponges that lack these cell types. Sponges are sessile animals with a complex canal system for filter-feeding. They undergo whole-body movements resembling "contractions" that lead to canal closure and water expulsion. Here, we combine 3D optical coherence microscopy, pharmacology, and functional proteomics to elucidate anatomy, molecular physiology, and control of these movements. We find them driven by the relaxation of actomyosin stress fibers in epithelial canal cells, which leads to whole-body deflation via collapse of the incurrent and expansion of the excurrent system, controlled by an Akt/NO/PKG/A pathway. A concomitant increase in reactive oxygen species and secretion of proteinases and cytokines indicate an inflammation-like state reminiscent of vascular endothelial cells experiencing oscillatory shear stress. This suggests an ancient relaxant-inflammatory response of perturbed fluid-carrying systems in animals. HighlightsO_LISponge deflation is driven by tension release in actomyosin stress fibers of epithelial pinacocytes C_LIO_LIAkt kinase/Nitric oxide/Protein kinase G/A regulate actomyosin relaxation C_LIO_LIAgitation-induced deflation coincides with an inflammatory state C_LIO_LIThe sponge relaxant-inflammatory response is evolutionary related to similar responses in the vertebrate vascular system C_LI

molecular biology↗

bioRxiv2023

Single-cell atlases of two lophotrochozoan larvae highlight their complex evolutionary histories

Pelagic larval stages are widespread across animals, yet it is unclear if larvae were present in the last common ancestor of animals or whether they evolved multiple times due to common selective pressures. Many marine larvae are at least superficially similar, they are small, swim through beating of ciliated bands and sense the environment with an apical organ structure. To understand these similarities, we have generated single cell atlases for marine larvae from two animal phyla and have compared their cell types. We found clear similarities among ciliary band cells and neurons of the apical organ in the two larvae pointing to possible homology of these structures suggesting a single origin of larvae within the clade analysed here (Lophotrochozoa). We also find several clade specific innovations in each larva, including distinct myocytes and shell gland cells in the oyster larva. Oyster shell gland cells express many novel genes which have made previous gene age estimates for trochophore larvae too young.

evolutionary biology↗

bioRxiv2022

Antibody escape and cryptic cross-domain stabilization in the SARS CoV-2 Omicron spike protein

The worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the repeated emergence of variants of concern. The Omicron variant has two dominant sub-lineages, BA.1 and BA.2, each with unprecedented numbers of nonsynonymous and indel spike protein mutations: 33 and 29, respectively. Some of these mutations individually increase transmissibility and enhance immune evasion, but their interactions within the Omicron mutational background is unknown. We characterize the molecular effects of all Omicron spike mutations on expression, human ACE2 receptor affinity, and neutralizing antibody recognition. We show that key mutations enable escape from neutralizing antibodies at a variety of epitopes. Stabilizing mutations in the N-terminal and S2 domains of the spike protein compensate for destabilizing mutations in the receptor binding domain, thereby enabling the record number of mutations in Omicron sub-lineages. Taken together, our results provide a comprehensive account of the mutational effects in the Omicron spike protein and illuminate previously unknown mechanisms of how the N-terminal domain can compensate for destabilizing mutations within the more evolutionarily constrained RBD.

immunology↗

bioRxiv2022

Detection of SARS-CoV-2 Omicron variant (B.1.1.529) infection of white-tailed deer

White-tailed deer (Odocoileus virginianus) are highly susceptible to infection by SARS-CoV-2, with multiple reports of widespread spillover of virus from humans to free-living deer. While the recently emerged SARS-CoV-2 B.1.1.529 Omicron variant of concern (VoC) has been shown to be notably more transmissible amongst humans, its ability to cause infection and spillover to non-human animals remains a challenge of concern. We found that 19 of the 131 (14.5%; 95% CI: 0.10-0.22) white-tailed deer opportunistically sampled on Staten Island, New York, between December 12, 2021, and January 31, 2022, were positive for SARS-CoV-2 specific serum antibodies using a surrogate virus neutralization assay, indicating prior exposure. The results also revealed strong evidence of age-dependence in antibody prevalence. A significantly ({chi}2, p < 0.001) greater proportion of yearling deer possessed neutralizing antibodies as compared with fawns (OR=12.7; 95% CI 4-37.5). Importantly, SARS-CoV-2 nucleic acid was detected in nasal swabs from seven of 68 (10.29%; 95% CI: 0.0-0.20) of the sampled deer, and whole-genome sequencing identified the SARS-CoV-2 Omicron VoC (B.1.1.529) is circulating amongst the white-tailed deer on Staten Island. Phylogenetic analyses revealed the deer Omicron sequences clustered closely with other, recently reported Omicron sequences recovered from infected humans in New York City and elsewhere, consistent with human to deer spillover. Interestingly, one individual deer was positive for viral RNA and had a high level of neutralizing antibodies, suggesting either rapid serological conversion during an ongoing infection or a "breakthrough" infection in a previously exposed animal. Together, our findings show that the SARS-CoV-2 B.1.1.529 Omicron VoC can infect white-tailed deer and highlights an urgent need for comprehensive surveillance of susceptible animal species to identify ecological transmission networks and better assess the potential risks of spillback to humans. Key FindingsThese studies provide strong evidence of infection of free-living white-tailed deer with the SARS-CoV-2 B.1.1.529 Omicron variant of concern on Staten Island, New York, and highlight an urgent need for investigations on human-to-animal-to-human spillovers/spillbacks as well as on better defining the expanding host-range of SARS-CoV-2 in non-human animals and the environment.

microbiology↗

bioRxiv2021

Regenerated crustacean limbs are precise replicas

Animals can regenerate complex organs, yet this frequently results in imprecise replicas of the original structure. In the crustacean Parhyale, embryonic and regenerating legs differ in gene expression dynamics but produce apparently similar mature structures. We examine the fidelity of Parhyale leg regeneration using complementary approaches to investigate microanatomy, sensory function, cellular composition and cell molecular profiles. We find that regeneration precisely replicates the complex microanatomy and spatial distribution of external sensory organs, and restores their sensory function. Single-nuclei sequencing shows that regenerated and uninjured legs are indistinguishable in terms of cell type composition and transcriptional profiles. This remarkable fidelity highlights the ability of organisms to achieve identical outcomes via distinct processes.

developmental biology↗

bioRxiv2021

Multiple spillovers and onward transmission of SARS-Cov-2 in free-living and captive White-tailed deer (Odocoileus virginianus)

Many animal species are susceptible to SARS-CoV-2 and could potentially act as reservoirs, yet transmission of the virus in non-human free-living animals has not been documented. White-tailed deer (Odocoileus virginianus), the predominant cervid in North America, are susceptible to SARS-CoV-2 infection, and experimentally infected fawns can transmit the virus. To test the hypothesis that SARS-CoV-2 may be circulating in deer, we tested 283 retropharyngeal lymph node (RPLN) samples collected from 151 free-living and 132 captive deer in Iowa from April 2020 through December of 2020 for the presence of SARS-CoV-2 RNA. Ninety-four of the 283 deer (33.2%; 95% CI: 28, 38.9) samples were positive for SARS-CoV-2 RNA as assessed by RT-PCR. Notably, between November 23, 2020 and January 10, 2021, 80 of 97 (82.5%; 95% CI 73.7, 88.8) RPLN samples had detectable SARS-CoV-2 RNA by RT-PCR. Whole genome sequencing of the 94 positive RPLN samples identified 12 SARS-CoV-2 lineages, with B.1.2 (n = 51; 54.5%), and B.1.311 (n = 19; 20%) accounting for ~75% of all samples. The geographic distribution and nesting of clusters of deer and human lineages strongly suggest multiple zooanthroponotic spillover events and deer-to-deer transmission. The discovery of sylvatic and enzootic SARS-CoV-2 transmission in deer has important implications for the ecology and long-term persistence, as well as the potential for spillover to other animals and spillback into humans. These findings highlight an urgent need for a robust and proactive "One Health" approach to obtaining a better understanding of the ecology and evolution of SARS-CoV-2. One-Sentence SummarySARS-CoV-2 was detected in one-third of sampled white-tailed deer in Iowa between September 2020 and January of 2021 that likely resulted from multiple human-to-deer spillover and deer-to-deer transmission events.

microbiology↗

bioRxiv2021

Analysis of the ARTIC version 3 and version 4 SARS-CoV-2 primers and their impact on the detection of the G142D amino acid substitution in the spike protein

The ARTIC Network provides a common resource of PCR primer sequences and recommendations for amplifying SARS-CoV-2 genomes. The initial tiling strategy was developed with the reference genome Wuhan-01, and subsequent iterations have addressed areas of low amplification and sequence drop out. Recently, a new version (V4) was released, based on new variant genome sequences, in response to the realization that some V3 primers were located in regions with key mutations. Herein, we compare the performance of the ARTIC V3 and V4 primer sets with a matched set of 663 SARS-CoV-2 clinical samples sequenced with an Illumina NovaSeq 6000 instrument. We observe general improvements in sequencing depth and quality, and improved resolution of the SNP causing the D950N variation in the spike protein. Importantly, we also find nearly universal presence of spike protein substitution G142D in Delta-lineage samples. Due to the prior release and widespread use of the ARTIC V3 primers during the initial surge of the Delta variant, it is likely that the G142D amino acid substitution is substantially underrepresented among early Delta variant genomes deposited in public repositories. In addition to the improved performance of the ARTIC V4 primer set, this study also illustrates the importance of the primer scheme in downstream analyses. ImportanceARTIC Network primers are commonly used by laboratories worldwide to amplify and sequence SARS-CoV-2 present in clinical samples. As new variants have evolved and spread, it was found that the V3 primer set poorly amplified several key mutations. In this report, we compare the results of sequencing a matched set of samples with the V3 and V4 primer sets. We find that adoption of the ARTIC V4 primer set is critical for accurate sequencing of the SARS-CoV-2 spike region. The absence of metadata describing the primer scheme used will negatively impact the downstream use of publicly available SARS-Cov-2 sequencing reads and assembled genomes.

bioinformatics↗

bioRxiv2021

Systems Biology Analysis of Human Genomes Points to Key Pathways Conferring Spina Bifida Risk

Spina bifida (SB) is a debilitating birth defect caused by multiple gene and environment interactions. Though SB shows non-Mendelian inheritance, genetic factors contribute to an estimated 70% of cases. Nevertheless, identifying human mutations conferring SB risk is challenging due to its relative rarity, genetic heterogeneity, incomplete penetrance and environmental influences that hamper GWAS approaches to untargeted discovery. Thus, SB genetic studies may suffer from population substructure and/or selection bias introduced by typical candidate gene searches. We report a population based, ancestry-matched whole-genome sequence analysis of SB genetic predisposition using a systems biology strategy to interrogate 298 case-control subject genomes (149 pairs). Genes that were enriched in likely gene disrupting (LGD), rare protein-coding variants were subjected to machine learning analysis to identify genes in which LGD variants occur with a different frequency in cases vs. controls and so discriminate between these groups. Those genes with high discriminatory potential for SB significantly enriched pathways pertaining to carbon metabolism, inflammation, innate immunity, cytoskeletal regulation and essential transcriptional regulation, indicating their impact on the pathogenesis of human SB. Additionally, interrogation of conserved non-coding sequences identified robust variant enrichment in regulatory regions of several transcription factors critical to embryonic development. This genome-wide perspective offers an effective approach to interrogation of coding and non-coding sequence variant contributions to rare complex genetic disorders.

genomics↗

bioRxiv2021

Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (Kd,app = 68 pM) to the receptor binding domain (RBD) of the spike protein and robustly neutralizes the virus in vitro. This antibody likely binds all three RBDs of the trimeric spike protein with a single IgG. Importantly, N3-1 equivalently binds spike proteins from emerging SARS-CoV-2 variants of concern, neutralizes UK variant B.1.1.7, and binds SARS-CoV spike with nanomolar affinity. Taken together, the strategies described herein will prove broadly applicable in interrogating adaptive immunity and developing rapid response biological countermeasures to emerging pathogens.

synthetic biology↗

bioRxiv2020

Limited window for donation of convalescent plasma with high live-virus neutralizing antibodies for COVID-19 immunotherapy

The optimal timeframe for donating convalescent plasma to be used for COVID-19 immunotherapy is unknown. To address this important knowledge deficit, we determined in vitro live-virus neutralizing capacity and persistence of IgM and IgG antibody responses against the receptor-binding domain and S1 ectodomain of the SARS-CoV-2 spike glycoprotein in 540 convalescent plasma samples obtained from 175 COVID-19 plasma donors for up to 142 days post-symptom onset. Robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 persist, in the aggregate, for at least 100 days post-symptom onset. However, a notable acceleration in decline in virus neutralization titers [≥]160, a value suitable for convalescent plasma therapy, was observed starting 60 days after first symptom onset. Together, these findings better define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor, including age and COVID-19 disease severity score. One Sentence SummaryEvaluation of SARS-CoV-2 anti-spike protein IgM, IgG, and live-virus neutralizing titer profiles reveals that the optimal window for donating convalescent plasma for use in immunotherapy is within the first 60 days of symptom onset.

immunology↗

bioRxiv2020

Relationship between Anti-Spike Protein Antibody Titers and SARS-CoV-2 In Vitro Virus Neutralization in Convalescent Plasma

Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer [≥]160 was 80% or greater with anti-RBD or anti-ECD titers of [≥]1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers [≥]160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of [≥]1:1350, and evidence of VN [≥]1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of [≥]1:1350 may provide critical information about protection against COVID-19 disease.

immunology↗

bioRxiv2020

Population genomic molecular epidemiological study of macrolide resistant Streptococcus pyogenes in Iceland,1995-2016: Identification of a large clonal population with a pbp2x mutation conferring reduced in vitro beta-lactam susceptibility

Resistance to macrolide antibiotics is a global concern in the treatment of Streptococcus pyogenes (Group A Streptococcus, GAS) infections. In Iceland, since the detection of the first macrolide-resistant isolate in 1998, three epidemic waves of macrolide-resistant GAS infections have occurred with peaks in 1999, 2004, and 2008. We conducted whole genome sequencing of all 1,575 available GAS macrolide-resistant clinical isolates of all infection types collected at the national reference laboratory in Reykjavik from 1998 to 2016. Among 1,515 erythromycin-resistant isolates, 90.3% were of only three emm types: emm4 (n = 713), emm6 (n = 324), and emm12 (n = 332), with each being predominant in a distinct epidemic peak. The antibiotic efflux pump genes, mef(A) and msr(D), were present on chimeric mobile genetic elements in 99.3% of the macrolide-resistant isolates of these emm types. Of note, in addition to macrolide resistance, virtually all emm12 isolates had a single amino acid substitution in penicillin-binding protein PBP2X that conferred a two-fold increased penicillin G and ampicillin MIC among isolates tested. We conclude that each of the three large epidemic peaks of macrolide-resistant GAS infections occurring in Iceland since 1998 was caused by the emergence and clonal expansion of progenitor strains, with macrolide resistance being conferred predominantly by inducible Mef(A)-Msr(D) drug efflux pumps. The occurrence of emm12 strains with macrolide resistance and decreased beta-lactam susceptibility was unexpected and is of public health concern. RepositoriesGenomic sequencing data for all 1,515 macrolide/erythromycin-resistant isolates were deposited into the National Center for Biotechnology Information Sequence Read Archive under bioproject accession PRJNA614628 and assembled sequences for composite elements {Phi}29854, {Phi}29862 and {Phi}29661 were deposited in Genbank under accessions ###, ### and ### respectively.

genomics↗

bioRxiv2020

Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas

We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. These genomes were from the viruses causing infections in the earliest recognized phase of the pandemic affecting Houston. Substantial viral genomic diversity was identified, which we interpret to mean that the virus was introduced into Houston many times independently by individuals who had traveled from different parts of the country and the world. The majority of viruses are apparent progeny of strains derived from Europe and Asia. We found no significant evidence of more virulent viral types, stressing the linkage between severe disease, underlying medical conditions, and perhaps host genetics. We discovered a signal of selection acting on the spike protein, the primary target of massive vaccine efforts worldwide. The data provide a critical resource for assessing virus evolution, the origin of new outbreaks, and the effect of host immune response. SignificanceCOVID-19, the disease caused by the SARS-CoV-2 virus, is a global pandemic. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. We identified no evidence that a particular strain or its progeny causes more severe disease, underscoring the connection between severe disease, underlying health conditions, and host genetics. Some amino acid replacements in the spike protein suggest positive immune selection is at work in shaping variation in this protein. Our analysis traces the early molecular architecture of SARS-CoV-2 in Houston, and will help us to understand the origin and trajectory of future infection spikes.

genetics↗