Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis

Haltom et al., Molecular Biology and Evolution, doi:10.1093/molbev/msaf211, Oct 2025
In silico and in vitro study showing that the SARS-CoV-2 orphan gene, ORF10, promotes pathogenesis and contributes to severe COVID-19. Authors analyzed millions of SARS-CoV-2 genomes, finding ORF10 is highly conserved, with mutations present in <5% of genomes. Four rare ORF10 mutations were found to be strongly associated with less severe clinical outcomes. In vitro, ORF10 expression in A549 and 293T human cells perturbed oxidative phosphorylation (OXPHOS) gene expression and disrupted immune gene networks. Authors propose that ORF10 expression leads to mitochondrial dysfunction and mitophagy, which in turn suppresses the host's MAVS-associated antiviral immune response.
Important missing comments or errors? Let us know.
Haltom et al., 1 Oct 2025, peer-reviewed, 19 authors. Contact: res2025@med.cornell.edu, mash@iastate.edu.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis
Jeffrey A Haltom, Nidia S Trovao, Joseph W Guarnieri, Vincent Pan, Urminder Singh, Sergey Tsoy, Collin A O’leary, Yaron Bram, Gabrielle A Widjaja, Zimu Cen, Robert Meller, Stephen B Baylin, Walter N Moss, Basil J Nikolau, Francisco J Enguita, Douglas C Wallace, Afshin Beheshti, Robert E Schwartz, Eve Syrkin Wurtele
Molecular Biology and Evolution, doi:10.1093/molbev/msaf211
Orphan genes, which encode species-specific proteins, are common but are rarely investigated. The SARS-CoV-2 orphan gene, ORF10, has been understudied; in vitro work suggests it may modulate innate immunity. Whether ORF10 influences COVID-19 outcomes in humans remained unknown. Here, analyzing millions of SARS-CoV-2 genomes, we find ORF10 sequences are identical to ancestral Wuhan-Hu-1 haplotype. In all variants of concern, <5% of genomes carry any ORF10 mutation. Despite limited statistical power due to the sparsity of mutated sequences, four ORF10 mutations were associated with less severe clinical outcomes in COVID-19 patients: three affect protein structure, one alters RNA structural dynamics. No mutations were linked to increased severity. ORF10 transcript levels in humans and human models are conditionally discordant from other SARS-CoV-2 genes. ORF10 expression in A549 and 293T cells significantly perturbs oxidative phosphorylation gene expression, disrupts immune gene networks, and shifts expression of 14 novel human transcripts. ORF10 is present in multiple Betacoronavirus pandemicum strains, but absent from SARS-CoV-1-like strains. We propose that this strain-restricted orphan gene contributes to severe COVID-19 in humans, with implications for future therapeutic strategies. These findings underscore the importance of studying recently evolved, potentially overlooked, viral orphan genes as a standard approach in pandemic preparedness.
Supplementary Material Supplementary material is available at Molecular Biology and Evolution online. Author Contributions Conceptualization, E.S.W., R.E.S., J.A.H., N.S. Conflict of Interest R.E.S. is on the scientific advisory board of Miromatrix Inc. and Lime Therapeutics and is a paid consultant and speaker for Alnylam Inc. D.C.W. is on the scientific advisory boards of Pano Therapeutics, Inc. and Medical Excellence Capital. Data Availability All data generated or analyzed during this study are included in this published article and its supplementary information files. Supplementary Table 1 , Supplementary Material online contains the 210,101 ORF10 sequences with mutation and clinical metadata. Supplementary Table 3 , Supplementary Material online contains SRA accession numbers for all samples used in the meta transcriptomics portion of this study. Supplementary data (Files 1-4), Supplementary Material online, including PDB files for the protein structures is available at https://iastate.box.com/ s/t1a64vhx9bl7jw4nbz4mfo4dvn0izedd . EB noncanonical human gene metadata is at https://github.com/urmi-21/Human_ orphan_genes and is available for visualization on UCSC gene browser (Nassar et al. 2023 ) at https://genome.ucsc.edu/s/ jahaltom/Orphan%20Genes . ORF10 expressing A549/HEK cell RNA-Seq data can be found on NCBI using accession GSE281252. Ethics Approval and Consent to Participate All data used in this study were publicly available. Consent for..
References
Aksamentov, Roemer, Hodcroft, Neher, Nextclade: clade assignment, mutation calling and quality control for viral genomes, J Open Source Softw, doi:10.21105/joss
Amicone, Borges, Alves, Isidro, Zé-Zé et al., Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution, Evol Med Public Health, doi:10.1093/emph/eoac010
An, Zhang, Mo, Luan, Tian et al., De novo genes with an lncRNA origin encode unique human brain developmental functionality, Nat Ecol Evol, doi:10.1038/s41559-022-01925-6
Andrews, Leary, Tompkins, Peterson, Haniff et al., A map of the SARS-CoV-2 RNA structurome, NAR Genom Bioinform, doi:10.1093/nargab/lqab043
Andrews, Roche, Moss, Scanfold: an approach for genomewide discovery of local RNA structural elements-applications to Zika virus and HIV, PeerJ, doi:10.7717/peerj.6136
Arendsee, Li, Wurtele, Coming of age: orphan genes in plants, Trends Plant Sci, doi:10.1016/j.tplants.2014.07.003
Baalsrud, Tørresen, Solbakken, Salzburger, Hanel et al., De novo gene evolution of antifreeze glycoproteins in codfishes revealed by whole genome sequence data, Mol Biol Evol, doi:10.1093/molbev/msx311
Baek, Dimaio, Anishchenko, Dauparas, Ovchinnikov et al., Accurate prediction of protein structures and interactions using a three-track neural network, Science, doi:10.1126/science.abj8754
Beachboard, Horner, Innate immune evasion strategies of DNA and RNA viruses, Curr Opin Microbiol, doi:10.1016/j.mib.2016.05.015
Benvenuto, Angeletti, Giovanetti, Bianchi, Pascarella et al., Evolutionary analysis of SARS-CoV-2: how mutation of non-structural protein 6 (NSP6) could affect viral autophagy, J Infect, doi:10.1016/j.jinf.2020.03.058
Bloom, Neher, Fitness effects of mutations to SARS-CoV-2 proteins, Virus Evol, doi:10.1093/ve/vead050
Boratto, Oliveira, Machado, Andrade, Baudoin et al., Yaravirus: a novel 80-nm virus infecting acanthamoeba castellanii, Proc Natl Acad Sci, doi:10.1073/pnas.2001637117
Bornberg-Bauer, Hlouchova, Lange, Protein-Carbohydrate Complexes and Glycosylation Sequences and Topology, Curr Opin Struct Biol, doi:10.1016/j.sbi.2020.11.010
Cagliani, Forni, Clerici, Sironi, Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses, Infect Genet Evol, doi:10.1016/j.meegid.2020.104353
Camacho, Coulouris, Avagyan, Ma, Papadopoulos et al., Blast+: architecture and applications, BMC Bioinformatics, doi:10.1186/1471-2105-10-421
Cannino, El-Khoury, Pirinen, Hutz, Jacobs et al., Glucose modulates respiratory complex I activity in response to acute mitochondrial dysfunction, J Biol Chem, doi:10.1074/jbc.M112.386060
Capella-Gutierrez, Silla-Martinez, Gabaldon, trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses, Bioinformatics, doi:10.1093/bioinformatics/btp348
Carabelli, Peacock, Thorne, Harvey, Hughes et al., SARS-CoV-2 variant biology: immune escape, transmission and fitness, Nat Rev Microbiol, doi:10.1038/s41579-022-00841-7
Carrazco-Montalvo, Herrera-Yela, Vallejo, Gutiérrez-Pallo, Armendáriz-Castillo et al., Omicron sub-lineages (BA.1.1.529 + BA.*) current status in Ecuador, Viruses, doi:10.3390/v14061177
Carvunis, Rolland, Wapinski, Calderwood, Yildirim et al., Proto-genes and de novo gene birth, Nature, doi:10.1038/nature11184
Chang, Rawlinson, Pitt, Taiaroa, Gleeson et al., Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection, Cell Rep, doi:10.1016/j.celrep.2021.109108
Chazal, Coronavirus, the king who wanted more than a crown: from common to the highly pathogenic SARS-CoV-2, is the key in the accessory genes?, Front Microbiol, doi:10.3389/fmicb.2021.682603
Chen, Bardes, Aronow, Jegga, ToppGene suite for gene list enrichment analysis and candidate gene prioritization, Nucleic Acids Res, doi:10.1093/nar/gkp427
Chen, Krinsky, Long, New genes as drivers of phenotypic evolution, Nat Rev Genet, doi:10.1038/nrg3521
Chowdhury, Bouatta, Biswas, Floristean, Kharkar et al., Single-sequence protein structure prediction using a language model and deep learning, Nat Biotechnol, doi:10.1038/s41587-022-01432-w
Crespo-Bellido, Duffy, The how of counter-defense: viral evolution to combat host immunity, Curr Opin Microbiol, doi:10.1016/j.mib.2023.102320
Darty, Ponty, Varna: interactive drawing and editing of the RNA secondary structure, Bioinformatics, doi:10.1093/bioinformatics/btp250
Dennis, Ballesteros, Robin, Schrader, Bast et al., Functional insights from the GC-poor genomes of two aphid parasitoids, Aphidius ervi and Lysiphlebus fabarum, BMC Genomics, doi:10.1186/s12864-020-6764-0
Domazet-Lošo, Tautz, A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns, Nature, doi:10.1038/nature09632
Elbe, Buckland-Merrett, Data, disease and diplomacy: GISAID's innovative contribution to global health, Global Chall, doi:10.1002/gch2.v1.1
Emanuel, Kirstin, Vedran, Asija, Theresa et al., Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy, iScience, doi:10.1016/j.isci.2021.102151
Emsley, Lohkamp, Scott, Cowtan, Features and development of coot, Acta Crystallogr D Biol Crystallogr, doi:10.1107/S0907444910007493
Fakhar, Liu, Pajerowska-Mukhtar, Mukhtar, The lost and found: unraveling the functions of orphan genes, J Dev Biol, doi:10.3390/jdb11020027
Fessler, Eckl, Schmitt, Mancilla, Meyer-Bender et al., A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol, Nature, doi:10.1038/s41586-020-2076-4
Fessler, Krumwiede, Jae, DELE1 tracks perturbed protein import and processing in human mitochondria, Nat Commun, doi:10.1038/s41467-022-29479-y
Finkel, Mizrahi, Nachshon, Weingarten-Gabbay, Morgenstern et al., The coding capacity of SARS-CoV-2, Nature, doi:10.1038/s41586-020-2739-1
Fischer, Riemer, The mitochondrial disulfide relay system: roles in oxidative protein folding and beyond, Int J Cell Biol, doi:10.1155/2013/742923
Frank, Duvezin-Caubet, Koob, Occhipinti, Jagasia et al., Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner, Biochim Biophys Acta, doi:10.1016/j.bbamcr.2012.08.007
Fumagalli, Padhiar, Meyer, Katneni, Bar et al., Analysis of 3.5 million SARS-CoV-2 sequences reveals unique mutational trends with consistent nucleotide and codon frequencies, Virol J, doi:10.1186/s12985-023-01982-8
Gordon, Hiatt, Bouhaddou, Rezelj, Ulferts et al., Comparative hostcoronavirus protein interaction networks reveal pan-viral disease mechanisms, Science, doi:10.1126/science.abe9403
Gordon, Jang, Bouhaddou, Xu, Obernier et al., A sars-cov-2 protein interaction map reveals targets for drug repurposing, Nature, doi:10.1038/s41586-020-2286-9
Gu, Bentley, Milligan, Almuqrin, Sharma et al., Recombinant sars-cov-2 lacking initiating and internal methionine codons within orf10 is attenuated in vivo, bioRxiv, doi:10.1101/2023.08.04.551973
Guarnieri, Dybas, Fazelinia, Kim, Frere et al., Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts, Sci Transl Med, doi:10.1126/scitranslmed.abq1533
Guarnieri, Haltom, Albrecht, Lie, Olali et al., SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19, Pharmacol Res, doi:10.1016/j.phrs.2024.107170
Gubala, Schmitz, Kearns, Vinh, Bornberg-Bauer et al., The Goddard and Saturn genes are essential for Drosophila male fertility and may have arisen de novo, Mol Biol Evol, doi:10.1093/molbev/msx057
Guo, Aviles, Liu, Tian, Unger et al., Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway, Nature, doi:10.1038/s41586-020-2078-2
Han, Zheng, Deng, Nan, Zhuang et al., Sars-cov-2 orf10 antagonizes stingdependent interferon activation and autophagy, J Med Virol, doi:10.1002/jmv.v94.11
Harris, Millman, Van Der Walt, Gommers, Virtanen et al., Array programming with NumPy, Nature, doi:10.1038/s41586-020-2649-2
Hassan, Attrish, Ghosh, Choudhury, Uversky et al., Notable sequence homology of the orf10 protein introspects the architecture of SARS-CoV-2, Int J Biol Macromol, doi:10.1016/j.ijbiomac.2021.03.199
Hu, Lu, Chen, Wang, Chen et al., K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis, Cell Res, doi:10.1038/cr.2011.145
Jeppesen, Toft-Bertelsen, Kledal, Rosenkilde, Amantadine inhibits known and novel ion channels encoded by SARS-CoV-2 in vitro, Commun Biol, doi:10.1038/s42003-021-02866-9
Jiang, Zhang, Meng, Xie, Li et al., SARS-CoV-2 orf9b suppresses type I interferon responses by targeting TOM70, Cell Mol Immunol, doi:10.1038/s41423-020-0514-8
Jr, Narayanan, Trovão, Guarnieri, Topper et al., A comprehensive SARS-CoV-2 and COVID-19 review, part 1: intracellular overdrive for SARS-CoV-2 infection, Eur J Hum Genet, doi:10.1038/s41431-022-01108-8
Jumper, Evans, Pritzel, Green, Figurnov et al., Highly accurate protein structure prediction with AlphaFold, Nature, doi:10.1038/s41586-021-03819-2
Karki, Lee, Mall, Pandian, Wang et al., ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection, Sci Immunol, doi:10.1126/sciimmunol.abo6294
Kato, Iwasaki, Takeshima, Maruzuru, Koyanagi et al., Identification of a novel neurovirulence factor encoded by the cryptic orphan gene UL31.6 of herpes simplex virus 1, J Virol, doi:10.1128/jvi.00747-24
Khan, Terenzi, Liu, Ghosh, Ye et al., A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon, Nat Commun, doi:10.1038/s41467-023-39091-3
Kim, Kim, Park, Chang, Chang et al., A high-resolution temporal atlas of the SARS-CoV-2 translatome and transcriptome, Nat Commun, doi:10.1038/s41467-021-25361-5
Koonin, Dolja, Krupovic, The logic of virus evolution, Cell Host Microbe, doi:10.1016/j.chom.2022.06.008
Kubli, Gustafsson, Mitochondria and mitophagy: the yin and yang of cell death control, Circ Res, doi:10.1161/CIRCRESAHA.112.265819
Lai, Proctor, Zhu, Meyer, R-chie: a web server and R package for visualizing RNA secondary structures, Nucleic Acids Res, doi:10.1093/nar/gks241
Lange, Patel, Heames, Damry, Saenger et al., Structural and functional characterization of a putative de novo gene in drosophila, Nat Commun, doi:10.1038/s41467-021-21667-6
Leary, Gaudieri, Parker, Chopra, James et al., Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level, Pathog Immun, doi:10.20411/pai.v6i2.460
Legendre, Alempic, Lartigue, Jeudy, Poirot et al., Pandoravirus celtis illustrates the microevolution processes at work in the giant Pandoraviridae genomes, Front Microbiol, doi:10.3389/fmicb.2019.00430
Lei, Dong, Ma, Xiao, Tian et al., Activation and evasion of type i interferon responses by SARS-CoV-2, Nat Commun, doi:10.1038/s41467-019-13993-7
Li, Foster, Gan, Nettleton, James et al., Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves, Plant J, doi:10.1111/tpj.2009.58.issue-3
Li, Hou, Ma, Wang, Wang et al., SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy, Cell Mol Immunol, doi:10.1038/s41423-021-00807-4
Li, Singh, Bhandary, Campbell, Arendsee et al., Foster thy young: enhanced prediction of orphan genes in assembled genomes, Nucleic Acids Res, doi:10.1093/nar/gkab1238
Li, Wurtele, The QQS orphan gene of Arabidopsis modulates carbon and nitrogen allocation in Soybean, Plant Biotechnol J, doi:10.1111/pbi.2015.13.issue-2
Liu, Hong, Parameswaran, Ernst, Marazzi et al., Human virus transcriptional regulators, Cell, doi:10.1016/j.cell.2020.06.023
Liu, Jia, Fang, Zhao, Differential expression of viral transcripts from single-cell RNA sequencing of moderate and severe COVID-19 patients and its implications for case severity, Front Microbiol, doi:10.3389/fmicb.2020.603509
Liu, Jiang, Wan, Hua, Li et al., Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?, PLoS Pathog, doi:10.1371/journal.ppat.1008421
Liu, Liang, Fung, Human coronavirus-229E,-OC43,-NL63, and-HKU1 (Coronaviridae), Encycl Virol, doi:10.1016/B978-0-12-809633-8.21501-X
Lorenz, Bernhart, Zu Siederdissen, Tafer, Flamm et al., ViennaRNA package 2.0, Algorithms Mol Biol, doi:10.1186/1748-7188-6-26
Lyly, Marjavaara, Kyttälä, Uusi-Rauva, Luiro et al., Deficiency of the INCL protein ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism, Hum Mol Genet, doi:10.1093/hmg/ddn028
Madeira, Pearce, Tivey, Basutkar, Lee et al., Search and sequence analysis tools services from EMBL-EBI in 2022, Nucleic Acids Res, doi:10.1093/nar/gkac240
Manrubia, The simple emergence of complex molecular function, Philos Trans A Math Phys Eng Sci, doi:10.1098/rsta.2020.0422
Mclysaght, Hurst, Open questions in the study of de novo genes: what, how and why, Nat Rev Genet, doi:10.1038/nrg.2016.78
Mena, Donahue, Vaites, Li, Rona et al., Orf10-cullin-2zyg11b complex is not required for SARS-CoV-2 infection, Proc Natl Acad Sci, doi:10.1073/pnas.2023157118
Mentzen, Wurtele, Regulon organization of Arabidopsis, BMC Plant Biol, doi:10.1186/1471-2229-8-99
Mercatelli, Giorgi, Geographic and genomic distribution of SARS-CoV-2 mutations, Front Microbiol, doi:10.3389/fmicb.2020.01800
Michaud, Madani, Fraser, A language model beats alphafold2 on orphans, Nat Biotechnol, doi:10.1038/s41587-022-01466-0
Minh, Schmidt, Chernomor, Schrempf, Woodhams et al., IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era, Mol Biol Evol, doi:10.1093/molbev/msaa015
Mohammadi, Shafiee, Shahzamani, Ranjbar, Alibakhshi et al., Novel and emerging mutations of SARS-CoV-2: biomedical implications, Biomed Pharmacother, doi:10.1016/j.biopha.2021.111599
Moustaqil, Ollivier, Chiu, Van Tol, Rudolffi-Soto et al., SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species, Emerg Microbes Infect, doi:10.1080/22221751.2020.1870414
Mészáros, Erdős, Dosztányi, Iupred2a: context-dependent prediction of protein disorder as a function of redox state and protein binding, Nucleic Acids Res, doi:10.1093/nar/gky384
Nasonovs, Garcia-Diaz, Bogenhagen, A549 cells contain enlarged mitochondria with independently functional clustered Importance of de novo gene evolution to emerging viral threats, PLoS One, doi:10.1371/journal.pone.0249047
Nassar, Barber, Benet-Pagès, Casper, Clawson et al., The UCSC genome browser database: 2023 update, Nucleic Acids Res, doi:10.1093/nar/gkac1072
Nelson, Ardern, Goldberg, Meng, Kuo et al., Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic, Elife, doi:10.7554/eLife.59633
Ovchinnikova, Balandin, Aleshina, Tagaev, Leonova et al., Aurelin, a novel antimicrobial peptide from jellyfish Aurelia aurita with structural features of defensins and channel-blocking toxins, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2006.07.078
Pancer, Milewska, Owczarek, Dabrowska, Kowalski et al., The SARS-CoV-2 orf10 is not essential in vitro or in vivo in humans, PLoS Pathog, doi:10.1371/journal.ppat.1008959
Patro, Duggal, Love, Irizarry, Kingsford, Salmon provides fast and bias-aware quantification of transcript expression, Nat Methods, doi:10.1038/nmeth.4197
Pekar, Lytras, Ghafari, Magee, Parker et al., The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2, Cell, doi:10.1016/j.cell.2025.03.035
Peng, Zhao, The origin and structural evolution of de novo genes in Drosophila, Nat Commun, doi:10.1038/s41467-024-45028-1
Qi, Zheng, Zhao, Hohenstein, Kandel et al., QQS orphan gene and its interactor NF-YC 4 reduce susceptibility to pathogens and pests, Plant Biotechnol J, doi:10.1111/pbi.2019.17.issue-1
Qin, Rao, Yuan, Wang, Zhao et al., SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis, Proc Natl Acad Sci, doi:10.1073/pnas.2122897119
Quinlan, Hall, Bedtools: a flexible suite of utilities for comparing genomic features, Bioinformatics
Ramløv, Friis, Antifreeze proteins volume 2: biochemistry, molecular biology and applications, doi:10.1007/978-3-030-41948-6_1
Rangan, Zheludev, Hagey, Pham, Wayment-Steele et al., RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses: a first look, RNA, doi:10.1261/rna.076141.120
Ravindra, Alfajaro, Gasque, Wei, Filler et al., Singlecell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes, PLOS Biol, doi:10.1371/journal.pbio.3001143
Reinhardt, Wanjiru, Brant, Saelao, Begun et al., De novo ORFs in drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences, PLoS Genet, doi:10.1371/journal.pgen.1003860
Rice, Longden, Bleasby, Emboss: the European molecular biology open software suite, Trends Genet, doi:10.1016/s0168-95250002024-2
Rihn, Merits, Bakshi, Turnbull, Wickenhagen et al., A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research, PLoS Biol, doi:10.1371/journal.pbio.3001091
Rivas, Clements, Eddy, Estimating the power of sequence covariation for detecting conserved RNA structure, Bioinformatics, doi:10.1093/bioinformatics/btaa080
Ruiz-Orera, Albà, Translation of small open reading frames: roles in regulation and evolutionary innovation, Trends Genet, doi:10.1016/j.tig.2018.12.003
Ruiz-Orera, Messeguer, Subirana, Alba, Long non-coding RNAS as a source of new peptides, eLife, doi:10.7554/eLife.03523
Saba, Adiba, Saha, Hosen, Chakraborty et al., An indepth in silico and immunoinformatics approach for designing a potential multi-epitope construct for the effective development of vaccine to combat against SARS-CoV-2 encompassing variants of concern and interest, Comput Biol Med, doi:10.1016/j.compbiomed.2021.104703
Sanchez, Linde, Coolon, Genome-wide effect of tetracycline, doxycycline and 4-epidoxycycline on gene expression in saccharomyces cerevisiae, Yeast, doi:10.1002/yea.v37.7-8
Sender, Bar-On, Gleizer, Bernshtein, Flamholz et al., The total number and mass of SARS-CoV-2 virions, Proc Natl Acad Sci, doi:10.1073/pnas.2024815118
Shin, Mukherjee, Grewe, Bojkova, Baek et al., Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity, Nature, doi:10.1038/s41586-020-2601-5
Shu, Mccauley, GISAID: global initiative on sharing all influenza data -from vision to reality, Euro Surveill, doi:10.2807/1560-7917.ES.2017.22.13.30494
Singh, Haltom, Guarnieri, Li, Seetharam et al., A pan-tissue, pan-disease compendium of human orphan genes, bioRxiv, doi:10.1101/2024.02.21.581488
Singh, Li, Seetharam, Wurtele, pyrpipe: a Python package for RNA-Seq workflows, NAR Genom Bioinform, doi:10.1093/nargab/lqab049
Singh, Wurtele, Genetic novelty: how new genes are born, eLife, doi:10.7554/eLife.55136
Singh, Yi, On the origin and evolution of SARS-CoV-2, Exp Mol Med, doi:10.1038/s12276-021-00604-z
Smet, Hendrix, Blasdel, Danis-Wlodarczyk, Lavigne, Pseudomonas predators: understanding and exploiting phage-host interactions, Nat Rev Microbiol, doi:10.1038/nrmicro.2017.61
Talbert, Armache, Henikoff, Viral histones: pickpocket's prize or primordial progenitor?, Epigenetics Chromatin, doi:10.1186/s13072-022-00454-7
Tautz, Domazet-Lošo, The evolutionary origin of orphan genes, Nat Rev Genet, doi:10.1038/nrg3053
Thorvaldsdottir, Robinson, Mesirov, Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration, Brief Bioinform, doi:10.1093/bib/bbs017
Topper, Guarnieri, Haltom, Chadburn, Cope et al., Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes, Proc Natl Acad Sci, doi:10.1073/pnas.2401968121
Vakirlis, Kupczok, Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins, Genome Res, doi:10.1101/gr.278977.124
Van Dongen, Graph clustering via a discrete uncoupling process, SIAM J Matrix Anal Appl, doi:10.1137/040608635
Van Oss, Carvunis, De novo gene birth, PLoS Genet, doi:10.1371/journal.pgen.1008160
Verbeke, Bolle, Arnould, Wallace, To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?, Nat Rev Cancer, doi:10.1038/nrc3365
Wang, Liu, Yang, Zhang, Jiao et al., SARS-CoV-2 orf10 impairs cilia by enhancing cul2zyg11b activity, J Cell Biol, doi:10.1083/jcb.202108015
Wong, Lebon, Basso, Kohlhaas, Nikkel et al., eIF2B activator prevents neurological defects caused by a chronic integrated stress response, eLife, doi:10.7554/eLife.42940
Wong, Lebon, Edalji, Lim, Sun et al., The small molecule ISRIB rescues the stability and activity of vanishing white matter disease eIF2B mutant complexes, eLife, doi:10.7554/eLife.32733
Wong, Perlman, Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses-are we our own worst enemy?, Nat Rev Immunol, doi:10.1038/s41577-021-00656-2
Wu, Hu, Xu, Chen, Guo et al., clusterProfiler 4.0: a universal enrichment tool for interpreting omics data, Innovation (Camb), doi:10.1016/j.xinn.2021.100141
Wu, Shi, Pan, Wu, Hou et al., SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting k63-linked ubiquitination of NEMO, Cell Rep, doi:10.1016/j.celrep.2021.108761
Xia, Cao, Xie, Zhang, Chen et al., Evasion of type I interferon by SARS-CoV-2, Cell Rep, doi:10.1016/j.celrep.2020.108234
Yi, Kim, Bleazard, Kim, Youk et al., Mutational spectrum of SARS-CoV-2 during the global pandemic, Exp Mol Med, doi:10.1038/s12276-021-00658-z
Yin, Fischer, Identification and investigation of ORFans in the viral world, BMC Genomics, doi:10.1186/1471-2164-9-1
Yu, Smith, Zhu, Guan, Lam, ggtree: an R package for visualization and annotation of phylogenetic trees with their covariates and other associated data, Methods Ecol Evol, doi:10.1111/mee3.2017.8.issue-1
Zandi, Orf9c and orf10 as accessory proteins of SARS-CoV-2 in immune evasion, Nat Rev Immunol, doi:10.1038/s41577-022-00715-2
Zhang, Cruz-Cosme, Zhuang, Liu, Liu et al., A systemic and molecular study of subcellular localization of SARS-CoV-2 proteins, Signal Transduct Target Ther, doi:10.1038/s41392-024-02041-6
Zhang, Li, Feng, Song, Dong et al., Structural insights into ORF10 recognition by ZYG11B, Biochem Biophys Res Commun, doi:10.1016/j.bbrc.2022.05.069
Zhao, Wang, Liu, Li, Wang et al., Leng8 regulation of mRNA processing, is responsible for the control of mitochondrial activity, Cell Biosci, doi:10.1186/s13578-021-00569-6
Zhou, Zhang, Zhang, Ye, Liu et al., Gene fusion as an important mechanism to generate new genes in the genus Oryza, Genome Biol, doi:10.1186/s13059-022-02696-w
DOI record: { "DOI": "10.1093/molbev/msaf211", "ISSN": [ "0737-4038", "1537-1719" ], "URL": "http://dx.doi.org/10.1093/molbev/msaf211", "abstract": "<jats:title>Abstract</jats:title>\n <jats:p>Orphan genes, which encode species-specific proteins, are common but are rarely investigated. The SARS-CoV-2 orphan gene, ORF10, has been understudied; in vitro work suggests it may modulate innate immunity. Whether ORF10 influences COVID-19 outcomes in humans remained unknown. Here, analyzing millions of SARS-CoV-2 genomes, we find ORF10 sequences are identical to ancestral Wuhan-Hu-1 haplotype. In all variants of concern, &amp;lt;5% of genomes carry any ORF10 mutation. Despite limited statistical power due to the sparsity of mutated sequences, four ORF10 mutations were associated with less severe clinical outcomes in COVID-19 patients: three affect protein structure, one alters RNA structural dynamics. No mutations were linked to increased severity. ORF10 transcript levels in humans and human models are conditionally discordant from other SARS-CoV-2 genes. ORF10 expression in A549 and 293T cells significantly perturbs oxidative phosphorylation gene expression, disrupts immune gene networks, and shifts expression of 14 novel human transcripts. ORF10 is present in multiple Betacoronavirus pandemicum strains, but absent from SARS-CoV-1-like strains. We propose that this strain-restricted orphan gene contributes to severe COVID-19 in humans, with implications for future therapeutic strategies. These findings underscore the importance of studying recently evolved, potentially overlooked, viral orphan genes as a standard approach in pandemic preparedness.</jats:p>", "article-number": "msaf211", "author": [ { "ORCID": "https://orcid.org/0000-0003-4534-2920", "affiliation": [ { "name": "Bioinformatics and Computational Biology Program, Genetics Program, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Department of Genetics, Development and Cell Biology, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children’s Hospital of Philadelphia , Philadelphia, PA 19104 ,", "place": [ "USA" ] }, { "name": "COVID-19 International Research Team , Medford, MA 02155 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Haltom", "given": "Jeffrey A", "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0002-2106-1166", "affiliation": [ { "name": "COVID-19 International Research Team , Medford, MA 02155 ,", "place": [ "USA" ] }, { "name": "Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health , Bethesda, MD 20892 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Trovao", "given": "Nidia S", "sequence": "additional" }, { "affiliation": [ { "name": "COVID-19 International Research Team , Medford, MA 02155 ,", "place": [ "USA" ] }, { "name": "Blue Marble Space Institute of Science , Seattle, WA 98104 ,", "place": [ "USA" ] }, { "name": "Guarnieri Research Group LLC , Philadelphia, PA 19146 ,", "place": [ "USA" ] } ], "family": "Guarnieri", "given": "Joseph W", "sequence": "additional" }, { "affiliation": [ { "name": "Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health , Bethesda, MD 20892 ,", "place": [ "USA" ] } ], "family": "Pan", "given": "Vincent", "sequence": "additional" }, { "affiliation": [ { "name": "Bioinformatics and Computational Biology Program, Genetics Program, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Department of Genetics, Development and Cell Biology, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "COVID-19 International Research Team , Medford, MA 02155 ,", "place": [ "USA" ] } ], "family": "Singh", "given": "Urminder", "sequence": "additional" }, { "affiliation": [ { "name": "Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine , New York, NY ,", "place": [ "USA" ] } ], "family": "Tsoy", "given": "Sergey", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-4246-6277", "affiliation": [ { "name": "Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Department of Biology and Chemistry, Cornell College , Mount Vernon, IA 52314 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "O’Leary", "given": "Collin A", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-9711-575X", "affiliation": [ { "name": "Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine , New York, NY ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Bram", "given": "Yaron", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children’s Hospital of Philadelphia , Philadelphia, PA 19104 ,", "place": [ "USA" ] } ], "family": "Widjaja", "given": "Gabrielle A", "sequence": "additional" }, { "affiliation": [ { "name": "Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children’s Hospital of Philadelphia , Philadelphia, PA 19104 ,", "place": [ "USA" ] }, { "name": "Department of Bioengineering, University of Pennsylvania , Philadelphia, PA 19104 ,", "place": [ "USA" ] } ], "family": "Cen", "given": "Zimu", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Neurobiology, Morehouse School of Medicine , Atlanta, GA 30310-1495 ,", "place": [ "USA" ] } ], "family": "Meller", "given": "Robert", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-3697-3798", "affiliation": [ { "name": "Department of Neurobiology, Morehouse School of Medicine , Atlanta, GA 30310-1495 ,", "place": [ "USA" ] }, { "name": "Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore, MD 21231, USA" } ], "authenticated-orcid": false, "family": "Baylin", "given": "Stephen B", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0001-6419-5570", "affiliation": [ { "name": "Bioinformatics and Computational Biology Program, Genetics Program, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Moss", "given": "Walter N", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-4672-7139", "affiliation": [ { "name": "Bioinformatics and Computational Biology Program, Genetics Program, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine , New York, NY ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Nikolau", "given": "Basil J", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-8072-8557", "affiliation": [ { "name": "Van Andel Research Institute , Grand Rapids, MI 49503, USA" } ], "authenticated-orcid": false, "family": "Enguita", "given": "Francisco J", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-7480-8278", "affiliation": [ { "name": "Center for Mitochondrial and Epigenomic Medicine, Division of Human Genetics, The Children’s Hospital of Philadelphia , Philadelphia, PA 19104 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Wallace", "given": "Douglas C", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-4643-531X", "affiliation": [ { "name": "COVID-19 International Research Team , Medford, MA 02155 ,", "place": [ "USA" ] }, { "name": "Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard , Cambridge, MA 02142 ,", "place": [ "USA" ] }, { "name": "Center for Space Biomedicine, McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh , Pittsburgh, PA 15219 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Beheshti", "given": "Afshin", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-5417-5995", "affiliation": [ { "name": "Division of Gastroenterology and Hepatology, Department of Medicine, Weill Cornell Medicine , New York, NY ,", "place": [ "USA" ] }, { "name": "Department of Physiology, Biophysics and Systems Biology, Weill Cornell Medicine , New York, NY ,", "place": [ "USA" ] }, { "name": "Department of Biomedical Engineering, Cornell University , Ithaca, NY ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Schwartz", "given": "Robert E", "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-1552-9495", "affiliation": [ { "name": "Bioinformatics and Computational Biology Program, Genetics Program, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "Department of Genetics, Development and Cell Biology, Iowa State University , Ames, IA 50011 ,", "place": [ "USA" ] }, { "name": "COVID-19 International Research Team , Medford, MA 02155 ,", "place": [ "USA" ] } ], "authenticated-orcid": false, "family": "Wurtele", "given": "Eve Syrkin", "sequence": "additional" } ], "container-title": "Molecular Biology and Evolution", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 10, 15 ] ], "date-time": "2025-10-15T20:29:07Z", "timestamp": 1760560147000 }, "deposited": { "date-parts": [ [ 2025, 10, 15 ] ], "date-time": "2025-10-15T20:29:09Z", "timestamp": 1760560149000 }, "editor": [ { "affiliation": [], "family": "Carvunis", "given": "Anne-Ruxandra", "sequence": "additional" } ], "funder": [ { "DOI": "10.13039/100000001", "award": [ "ACI-1548562" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100000001", "id-type": "DOI" } ], "name": "National Science Foundation" }, { "DOI": "10.13039/100000002", "award": [ "NIAID 2R01AI107301", "NIDDK R01DK121072" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100000002", "id-type": "DOI" } ], "name": "NIH" }, { "award": [ "R01GM133810" ], "name": "NIH/NIGMS" }, { "DOI": "10.13039/100000005", "award": [ "W81XWH-21-1-0128" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100000005", "id-type": "DOI" } ], "name": "DOD" }, { "DOI": "10.13039/100000865", "award": [ "INV-046722" ], "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100000865", "id-type": "DOI" } ], "name": "Bill & Melinda Gates Foundation" } ], "indexed": { "date-parts": [ [ 2025, 10, 16 ] ], "date-time": "2025-10-16T01:03:32Z", "timestamp": 1760576612608, "version": "build-2065373602" }, "is-referenced-by-count": 0, "issue": "10", "issued": { "date-parts": [ [ 2025, 10, 1 ] ] }, "journal-issue": { "issue": "10", "published-print": { "date-parts": [ [ 2025, 10, 1 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by-nc/4.0/", "content-version": "vor", "delay-in-days": 14, "start": { "date-parts": [ [ 2025, 10, 15 ] ], "date-time": "2025-10-15T00:00:00Z", "timestamp": 1760486400000 } } ], "link": [ { "URL": "https://academic.oup.com/mbe/article-pdf/42/10/msaf211/64712237/msaf211.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "syndication" }, { "URL": "https://academic.oup.com/mbe/article-pdf/42/10/msaf211/64712237/msaf211.pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "286", "original-title": [], "prefix": "10.1093", "published": { "date-parts": [ [ 2025, 10, 1 ] ] }, "published-online": { "date-parts": [ [ 2025, 10, 15 ] ] }, "published-other": { "date-parts": [ [ 2025, 10 ] ] }, "published-print": { "date-parts": [ [ 2025, 10, 1 ] ] }, "publisher": "Oxford University Press (OUP)", "reference": [ { "DOI": "10.21105/joss", "article-title": "Nextclade: clade assignment, mutation calling and quality control for viral genomes", "author": "Aksamentov", "doi-asserted-by": "publisher", "first-page": "3773", "issue": "67", "journal-title": "J Open Source Softw", "key": "2025101516290195200_msaf211-B1", "volume": "6", "year": "2021" }, { "DOI": "10.1093/emph/eoac010", "article-title": "Mutation rate of SARS-CoV-2 and emergence of mutators during experimental evolution", "author": "Amicone", "doi-asserted-by": "publisher", "first-page": "142", "issue": "1", "journal-title": "Evol Med Public Health", "key": "2025101516290195200_msaf211-B2", "volume": "10", "year": "2022" }, { "DOI": "10.1038/s41559-022-01925-6", "article-title": "De novo genes with an lncRNA origin encode unique human brain developmental functionality", "author": "An", "doi-asserted-by": "publisher", "first-page": "264", "issue": "2", "journal-title": "Nat Ecol Evol", "key": "2025101516290195200_msaf211-B3", "volume": "7", "year": "2023" }, { "DOI": "10.1093/nargab/lqab043", "article-title": "A map of the SARS-CoV-2 RNA structurome", "author": "Andrews", "doi-asserted-by": "publisher", "first-page": "lqab043", "issue": "2", "journal-title": "NAR Genom Bioinform", "key": "2025101516290195200_msaf211-B4", "volume": "3", "year": "2021" }, { "DOI": "10.7717/peerj.6136", "article-title": "Scanfold: an approach for genome-wide discovery of local RNA structural elements-applications to Zika virus and HIV", "author": "Andrews", "doi-asserted-by": "publisher", "first-page": "e6136", "issue": "6316", "journal-title": "PeerJ", "key": "2025101516290195200_msaf211-B5", "volume": "6", "year": "2018" }, { "DOI": "10.1016/j.tplants.2014.07.003", "article-title": "Coming of age: orphan genes in plants", "author": "Arendsee", "doi-asserted-by": "publisher", "first-page": "698", "issue": "11", "journal-title": "Trends Plant Sci", "key": "2025101516290195200_msaf211-B6", "volume": "19", "year": "2014" }, { "DOI": "10.1093/molbev/msx311", "article-title": "De novo gene evolution of antifreeze glycoproteins in codfishes revealed by whole genome sequence data", "author": "Baalsrud", "doi-asserted-by": "publisher", "first-page": "593", "issue": "3", "journal-title": "Mol Biol Evol", "key": "2025101516290195200_msaf211-B7", "volume": "35", "year": "2018" }, { "DOI": "10.1126/science.abj8754", "article-title": "Accurate prediction of protein structures and interactions using a three-track neural network", "author": "Baek", "doi-asserted-by": "publisher", "first-page": "871", "issue": "6557", "journal-title": "Science", "key": "2025101516290195200_msaf211-B8", "volume": "373", "year": "2021" }, { "DOI": "10.1016/j.mib.2016.05.015", "article-title": "Innate immune evasion strategies of DNA and RNA viruses", "author": "Beachboard", "doi-asserted-by": "publisher", "first-page": "113", "journal-title": "Curr Opin Microbiol", "key": "2025101516290195200_msaf211-B9", "volume": "32", "year": "2016" }, { "DOI": "10.1016/j.jinf.2020.03.058", "article-title": "Evolutionary analysis of SARS-CoV-2: how mutation of non-structural protein 6 (NSP6) could affect viral autophagy", "author": "Benvenuto", "doi-asserted-by": "publisher", "first-page": "e24", "issue": "1", "journal-title": "J Infect", "key": "2025101516290195200_msaf211-B10", "volume": "81", "year": "2020" }, { "DOI": "10.1093/ve/vead050", "article-title": "Fitness effects of mutations to SARS-CoV-2 proteins", "author": "Bloom", "doi-asserted-by": "publisher", "first-page": "055", "issue": "2", "journal-title": "Virus Evol", "key": "2025101516290195200_msaf211-B11", "volume": "9", "year": "2023" }, { "DOI": "10.1073/pnas.2001637117", "article-title": "Yaravirus: a novel 80-nm virus infecting acanthamoeba castellanii", "author": "Boratto", "doi-asserted-by": "publisher", "first-page": "16579", "issue": "28", "journal-title": "Proc Natl Acad Sci USA", "key": "2025101516290195200_msaf211-B12", "volume": "117", "year": "2020" }, { "DOI": "10.1016/j.sbi.2020.11.010", "article-title": "Structure and function of naturally evolved de novo proteins", "author": "Bornberg-Bauer", "doi-asserted-by": "publisher", "first-page": "175", "journal-title": "Curr Opin Struct Biol", "key": "2025101516290195200_msaf211-B13", "volume": "68", "year": "2021" }, { "DOI": "10.1016/j.meegid.2020.104353", "article-title": "Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses", "author": "Cagliani", "doi-asserted-by": "publisher", "first-page": "104353", "issue": "10224", "journal-title": "Infect Genet Evol", "key": "2025101516290195200_msaf211-B14", "volume": "83", "year": "2020" }, { "DOI": "10.1186/1471-2105-10-421", "article-title": "Blast+: architecture and applications", "author": "Camacho", "doi-asserted-by": "publisher", "first-page": "421", "issue": "1", "journal-title": "BMC Bioinformatics", "key": "2025101516290195200_msaf211-B15", "volume": "10", "year": "2009" }, { "DOI": "10.1074/jbc.M112.386060", "article-title": "Glucose modulates respiratory complex I activity in response to acute mitochondrial dysfunction", "author": "Cannino", "doi-asserted-by": "publisher", "first-page": "38729", "issue": "46", "journal-title": "J Biol Chem", "key": "2025101516290195200_msaf211-B16", "volume": "287", "year": "2012" }, { "DOI": "10.1093/bioinformatics/btp348", "article-title": "trimAl: a tool for automated alignment trimming in large-scale phylogenetic analyses", "author": "Capella-Gutierrez", "doi-asserted-by": "publisher", "first-page": "1972", "issue": "15", "journal-title": "Bioinformatics", "key": "2025101516290195200_msaf211-B17", "volume": "25", "year": "2009" }, { "DOI": "10.1038/s41579-022-00841-7", "article-title": "SARS-CoV-2 variant biology: immune escape, transmission and fitness", "author": "Carabelli", "doi-asserted-by": "publisher", "first-page": "162", "issue": "3", "journal-title": "Nat Rev Microbiol", "key": "2025101516290195200_msaf211-B18", "volume": "21", "year": "2023" }, { "DOI": "10.3390/v14061177", "article-title": "Omicron sub-lineages (BA.1.1.529 + BA.*) current status in Ecuador", "author": "Carrazco-Montalvo", "doi-asserted-by": "publisher", "first-page": "1177", "issue": "6", "journal-title": "Viruses", "key": "2025101516290195200_msaf211-B19", "volume": "14", "year": "2022" }, { "DOI": "10.1038/nature11184", "article-title": "Proto-genes and de novo gene birth", "author": "Carvunis", "doi-asserted-by": "publisher", "first-page": "370", "issue": "7407", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B20", "volume": "487", "year": "2012" }, { "DOI": "10.1016/j.celrep.2021.109108", "article-title": "Transcriptional and epi-transcriptional dynamics of SARS-CoV-2 during cellular infection", "author": "Chang", "doi-asserted-by": "publisher", "first-page": "109108", "issue": "6", "journal-title": "Cell Rep", "key": "2025101516290195200_msaf211-B21", "volume": "35", "year": "2021" }, { "DOI": "10.3389/fmicb.2021.682603", "article-title": "Coronavirus, the king who wanted more than a crown: from common to the highly pathogenic SARS-CoV-2, is the key in the accessory genes?", "author": "Chazal", "doi-asserted-by": "publisher", "first-page": "682603", "journal-title": "Front Microbiol", "key": "2025101516290195200_msaf211-B22", "volume": "12", "year": "2021" }, { "DOI": "10.1093/nar/gkp427", "article-title": "ToppGene suite for gene list enrichment analysis and candidate gene prioritization", "author": "Chen", "doi-asserted-by": "publisher", "first-page": "W305", "issue": "Web Server", "journal-title": "Nucleic Acids Res", "key": "2025101516290195200_msaf211-B23", "volume": "37", "year": "2009" }, { "DOI": "10.1038/nrg3521", "article-title": "New genes as drivers of phenotypic evolution", "author": "Chen", "doi-asserted-by": "publisher", "first-page": "645", "issue": "9", "journal-title": "Nat Rev Genet", "key": "2025101516290195200_msaf211-B24", "volume": "14", "year": "2013" }, { "DOI": "10.1038/s41587-022-01432-w", "article-title": "Single-sequence protein structure prediction using a language model and deep learning", "author": "Chowdhury", "doi-asserted-by": "publisher", "first-page": "1617", "issue": "11", "journal-title": "Nat Biotechnol", "key": "2025101516290195200_msaf211-B25", "volume": "40", "year": "2022" }, { "DOI": "10.1016/j.mib.2023.102320", "article-title": "The how of counter-defense: viral evolution to combat host immunity", "author": "Crespo-Bellido", "doi-asserted-by": "publisher", "first-page": "102320", "issue": "102320", "journal-title": "Curr Opin Microbiol", "key": "2025101516290195200_msaf211-B26", "volume": "74", "year": "2023" }, { "DOI": "10.1093/bioinformatics/btp250", "article-title": "Varna: interactive drawing and editing of the RNA secondary structure", "author": "Darty", "doi-asserted-by": "publisher", "first-page": "1974", "issue": "15", "journal-title": "Bioinformatics", "key": "2025101516290195200_msaf211-B27", "volume": "25", "year": "2009" }, { "DOI": "10.1186/s12864-020-6764-0", "article-title": "Functional insights from the GC-poor genomes of two aphid parasitoids, Aphidius ervi and Lysiphlebus fabarum", "author": "Dennis", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "BMC Genomics", "key": "2025101516290195200_msaf211-B28", "volume": "21", "year": "2020" }, { "DOI": "10.1038/nrmicro.2017.61", "article-title": "Pseudomonas predators: understanding and exploiting phage–host interactions", "author": "De Smet", "doi-asserted-by": "publisher", "first-page": "517", "issue": "9", "journal-title": "Nat Rev Microbiol", "key": "2025101516290195200_msaf211-B29", "volume": "15", "year": "2017" }, { "DOI": "10.1038/nature09632", "article-title": "A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns", "author": "Domazet-Lošo", "doi-asserted-by": "publisher", "first-page": "815", "issue": "7325", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B30", "volume": "468", "year": "2010" }, { "DOI": "10.1002/gch2.v1.1", "article-title": "Data, disease and diplomacy: GISAID’s innovative contribution to global health", "author": "Elbe", "doi-asserted-by": "publisher", "first-page": "33", "issue": "1", "journal-title": "Global Chall", "key": "2025101516290195200_msaf211-B31", "volume": "1", "year": "2017" }, { "DOI": "10.1016/j.isci.2021.102151", "article-title": "Transcriptomic profiling of SARS-CoV-2 infected human cell lines identifies HSP90 as target for COVID-19 therapy", "author": "Emanuel", "doi-asserted-by": "publisher", "issue": "3", "journal-title": "iScience", "key": "2025101516290195200_msaf211-B32", "volume": "24" }, { "DOI": "10.1107/S0907444910007493", "article-title": "Features and development of coot", "author": "Emsley", "doi-asserted-by": "publisher", "first-page": "486", "issue": "4", "journal-title": "Acta Crystallogr D Biol Crystallogr", "key": "2025101516290195200_msaf211-B33", "volume": "66", "year": "2010" }, { "DOI": "10.3390/jdb11020027", "article-title": "The lost and found: unraveling the functions of orphan genes", "author": "Fakhar", "doi-asserted-by": "publisher", "first-page": "27", "issue": "2", "journal-title": "J Dev Biol", "key": "2025101516290195200_msaf211-B34", "volume": "11", "year": "2023" }, { "DOI": "10.1038/s41586-020-2076-4", "article-title": "A pathway coordinated by DELE1 relays mitochondrial stress to the cytosol", "author": "Fessler", "doi-asserted-by": "publisher", "first-page": "433", "issue": "7799", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B35", "volume": "579", "year": "2020" }, { "DOI": "10.1038/s41467-022-29479-y", "article-title": "DELE1 tracks perturbed protein import and processing in human mitochondria", "author": "Fessler", "doi-asserted-by": "publisher", "first-page": "1853", "issue": "1", "journal-title": "Nat Commun", "key": "2025101516290195200_msaf211-B36", "volume": "13", "year": "2022" }, { "DOI": "10.1038/s41586-020-2739-1", "article-title": "The coding capacity of SARS-CoV-2", "author": "Finkel", "doi-asserted-by": "publisher", "first-page": "125", "issue": "7840", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B37", "volume": "589", "year": "2021" }, { "DOI": "10.1155/2013/742923", "article-title": "The mitochondrial disulfide relay system: roles in oxidative protein folding and beyond", "author": "Fischer", "doi-asserted-by": "publisher", "first-page": "1", "issue": "23", "journal-title": "Int J Cell Biol", "key": "2025101516290195200_msaf211-B38", "volume": "2013", "year": "2013" }, { "DOI": "10.1016/j.bbamcr.2012.08.007", "article-title": "Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner", "author": "Frank", "doi-asserted-by": "publisher", "first-page": "2297", "issue": "12", "journal-title": "Biochim Biophys Acta", "key": "2025101516290195200_msaf211-B39", "volume": "1823", "year": "2012" }, { "DOI": "10.1186/s12985-023-01982-8", "article-title": "Analysis of 3.5 million SARS-CoV-2 sequences reveals unique mutational trends with consistent nucleotide and codon frequencies", "author": "Fumagalli", "doi-asserted-by": "publisher", "first-page": "31", "issue": "1", "journal-title": "Virol J", "key": "2025101516290195200_msaf211-B40", "volume": "20", "year": "2023" }, { "DOI": "10.1126/science.abe9403", "article-title": "Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms", "author": "Gordon", "doi-asserted-by": "publisher", "first-page": "eabe9403", "issue": "6521", "journal-title": "Science", "key": "2025101516290195200_msaf211-B41", "volume": "370", "year": "2020" }, { "DOI": "10.1038/s41586-020-2286-9", "article-title": "A sars-cov-2 protein interaction map reveals targets for drug repurposing", "author": "Gordon", "doi-asserted-by": "publisher", "first-page": "459", "issue": "7816", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B42", "volume": "583", "year": "2020" }, { "DOI": "10.1101/2023.08.04.551973", "author": "Gu", "doi-asserted-by": "publisher", "key": "2025101516290195200_msaf211-B43" }, { "DOI": "10.1126/scitranslmed.abq1533", "article-title": "Core mitochondrial genes are down-regulated during SARS-CoV-2 infection of rodent and human hosts", "author": "Guarnieri", "doi-asserted-by": "publisher", "first-page": "eabq1533", "issue": "708", "journal-title": "Sci Transl Med", "key": "2025101516290195200_msaf211-B44", "volume": "15", "year": "2023" }, { "DOI": "10.1016/j.phrs.2024.107170", "article-title": "SARS-CoV-2 mitochondrial metabolic and epigenomic reprogramming in COVID-19", "author": "Guarnieri", "doi-asserted-by": "publisher", "first-page": "107170", "issue": "708", "journal-title": "Pharmacol Res", "key": "2025101516290195200_msaf211-B45", "volume": "204", "year": "2024" }, { "DOI": "10.1093/molbev/msx057", "article-title": "The Goddard and Saturn genes are essential for Drosophila male fertility and may have arisen de novo", "author": "Gubala", "doi-asserted-by": "publisher", "first-page": "1066", "issue": "5", "journal-title": "Mol Biol Evol", "key": "2025101516290195200_msaf211-B46", "volume": "34", "year": "2017" }, { "DOI": "10.1038/s41586-020-2078-2", "article-title": "Mitochondrial stress is relayed to the cytosol by an OMA1-DELE1-HRI pathway", "author": "Guo", "doi-asserted-by": "publisher", "first-page": "427", "issue": "7799", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B47", "volume": "579", "year": "2020" }, { "DOI": "10.1002/jmv.v94.11", "article-title": "Sars-cov-2 orf10 antagonizes sting-dependent interferon activation and autophagy", "author": "Han", "doi-asserted-by": "publisher", "first-page": "5174", "issue": "11", "journal-title": "J Med Virol", "key": "2025101516290195200_msaf211-B48", "volume": "94", "year": "2022" }, { "DOI": "10.1038/s41586-020-2649-2", "article-title": "Array programming with NumPy", "author": "Harris", "doi-asserted-by": "publisher", "first-page": "357", "issue": "7825", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B49", "volume": "585", "year": "2020" }, { "DOI": "10.1016/j.ijbiomac.2021.03.199", "article-title": "Notable sequence homology of the orf10 protein introspects the architecture of SARS-CoV-2", "author": "Hassan", "doi-asserted-by": "publisher", "first-page": "801", "issue": "5", "journal-title": "Int J Biol Macromol", "key": "2025101516290195200_msaf211-B50", "volume": "181", "year": "2021" }, { "DOI": "10.1038/cr.2011.145", "article-title": "K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic switch from oxidative phosphorylation to glycolysis", "author": "Hu", "doi-asserted-by": "publisher", "first-page": "399", "issue": "2", "journal-title": "Cell Res", "key": "2025101516290195200_msaf211-B51", "volume": "22", "year": "2012" }, { "DOI": "10.1038/s41431-022-01108-8", "article-title": "A comprehensive SARS-CoV-2 and COVID-19 review, part 1: intracellular overdrive for SARS-CoV-2 infection", "author": "Jamison", "doi-asserted-by": "publisher", "first-page": "889", "issue": "8", "journal-title": "Eur J Hum Genet", "key": "2025101516290195200_msaf211-B52", "volume": "30", "year": "2022" }, { "DOI": "10.1038/s42003-021-02866-9", "article-title": "Amantadine inhibits known and novel ion channels encoded by SARS-CoV-2 in vitro", "author": "Jeppesen", "doi-asserted-by": "publisher", "first-page": "1347", "issue": "1", "journal-title": "Commun Biol", "key": "2025101516290195200_msaf211-B53", "volume": "4", "year": "2021" }, { "DOI": "10.1038/s41423-020-0514-8", "article-title": "SARS-CoV-2 orf9b suppresses type I interferon responses by targeting TOM70", "author": "Jiang", "doi-asserted-by": "publisher", "first-page": "998", "issue": "9", "journal-title": "Cell Mol Immunol", "key": "2025101516290195200_msaf211-B54", "volume": "17", "year": "2020" }, { "DOI": "10.1038/s41586-021-03819-2", "article-title": "Highly accurate protein structure prediction with AlphaFold", "author": "Jumper", "doi-asserted-by": "publisher", "first-page": "583", "issue": "7873", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B55", "volume": "596", "year": "2021" }, { "DOI": "10.1126/sciimmunol.abo6294", "article-title": "ZBP1-dependent inflammatory cell death, PANoptosis, and cytokine storm disrupt IFN therapeutic efficacy during coronavirus infection", "author": "Karki", "doi-asserted-by": "publisher", "first-page": "eabo6294", "issue": "74", "journal-title": "Sci Immunol", "key": "2025101516290195200_msaf211-B56", "volume": "7", "year": "2022" }, { "DOI": "10.1128/jvi.00747-24", "article-title": "Identification of a novel neurovirulence factor encoded by the cryptic orphan gene UL31.6 of herpes simplex virus 1", "author": "Kato", "doi-asserted-by": "publisher", "first-page": "e0074724", "issue": "7", "journal-title": "J Virol", "key": "2025101516290195200_msaf211-B57", "volume": "98", "year": "2024" }, { "DOI": "10.1038/s41467-023-39091-3", "article-title": "A viral pan-end RNA element and host complex define a SARS-CoV-2 regulon", "author": "Khan", "doi-asserted-by": "publisher", "first-page": "3385", "issue": "1", "journal-title": "Nat Commun", "key": "2025101516290195200_msaf211-B58", "volume": "14", "year": "2023" }, { "DOI": "10.1038/s41467-021-25361-5", "article-title": "A high-resolution temporal atlas of the SARS-CoV-2 translatome and transcriptome", "author": "Kim", "doi-asserted-by": "publisher", "first-page": "5120", "issue": "1", "journal-title": "Nat Commun", "key": "2025101516290195200_msaf211-B59", "volume": "12", "year": "2021" }, { "DOI": "10.1016/j.chom.2022.06.008", "article-title": "The logic of virus evolution", "author": "Koonin", "doi-asserted-by": "publisher", "first-page": "917", "issue": "7", "journal-title": "Cell Host Microbe", "key": "2025101516290195200_msaf211-B60", "volume": "30", "year": "2022" }, { "DOI": "10.1161/CIRCRESAHA.112.265819", "article-title": "Mitochondria and mitophagy: the yin and yang of cell death control", "author": "Kubli", "doi-asserted-by": "publisher", "first-page": "1208", "issue": "9", "journal-title": "Circ Res", "key": "2025101516290195200_msaf211-B61", "volume": "111", "year": "2012" }, { "DOI": "10.1093/nar/gks241", "article-title": "R-chie: a web server and R package for visualizing RNA secondary structures", "author": "Lai", "doi-asserted-by": "publisher", "first-page": "e95", "issue": "12", "journal-title": "Nucleic Acids Res", "key": "2025101516290195200_msaf211-B62", "volume": "40", "year": "2012" }, { "DOI": "10.1038/s41467-021-21667-6", "article-title": "Structural and functional characterization of a putative de novo gene in drosophila", "author": "Lange", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Nat Commun", "key": "2025101516290195200_msaf211-B63", "volume": "12", "year": "2021" }, { "DOI": "10.20411/pai.v6i2.460", "article-title": "Generation of a novel SARS-CoV-2 sub-genomic RNA due to the R203K/G204R variant in nucleocapsid: homologous recombination has potential to change SARS-CoV-2 at both protein and RNA level", "author": "Leary", "doi-asserted-by": "publisher", "first-page": "27", "issue": "2", "journal-title": "Pathog Immun", "key": "2025101516290195200_msaf211-B64", "volume": "6" }, { "DOI": "10.3389/fmicb.2019.00430", "article-title": "Pandoravirus celtis illustrates the microevolution processes at work in the giant Pandoraviridae genomes", "author": "Legendre", "doi-asserted-by": "publisher", "journal-title": "Front Microbiol", "key": "2025101516290195200_msaf211-B65", "volume": "10", "year": "2019" }, { "DOI": "10.1038/s41467-019-13993-7", "article-title": "Activation and evasion of type i interferon responses by SARS-CoV-2", "author": "Lei", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Nat Commun", "key": "2025101516290195200_msaf211-B66", "volume": "11", "year": "2020" }, { "DOI": "10.1093/nar/gkab1238", "article-title": "Foster thy young: enhanced prediction of orphan genes in assembled genomes", "author": "Li", "doi-asserted-by": "publisher", "first-page": "e37", "issue": "7", "journal-title": "Nucleic Acids Res", "key": "2025101516290195200_msaf211-B67", "volume": "50", "year": "2022" }, { "DOI": "10.1111/tpj.2009.58.issue-3", "article-title": "Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves", "author": "Li", "doi-asserted-by": "publisher", "first-page": "485", "issue": "3", "journal-title": "Plant J", "key": "2025101516290195200_msaf211-B68", "volume": "58", "year": "2009" }, { "DOI": "10.1111/pbi.2015.13.issue-2", "article-title": "The QQS orphan gene of Arabidopsis modulates carbon and nitrogen allocation in Soybean", "author": "Li", "doi-asserted-by": "publisher", "first-page": "177", "issue": "2", "journal-title": "Plant Biotechnol J", "key": "2025101516290195200_msaf211-B69", "volume": "13", "year": "2015" }, { "DOI": "10.1038/s41423-021-00807-4", "article-title": "SARS-CoV-2 ORF10 suppresses the antiviral innate immune response by degrading MAVS through mitophagy", "author": "Li", "doi-asserted-by": "publisher", "first-page": "67", "issue": "1", "journal-title": "Cell Mol Immunol", "key": "2025101516290195200_msaf211-B70", "volume": "19", "year": "2022" }, { "DOI": "10.1016/B978-0-12-809633-8.21501-X", "article-title": "Human coronavirus-229E,-OC43,-NL63, and-HKU1 (Coronaviridae)", "author": "Liu", "doi-asserted-by": "publisher", "first-page": "428", "journal-title": "Encycl Virol", "key": "2025101516290195200_msaf211-B71", "year": "2021" }, { "DOI": "10.1371/journal.ppat.1008421", "article-title": "Are pangolins the intermediate host of the 2019 novel coronavirus (SARS-CoV-2)?", "author": "Liu", "doi-asserted-by": "publisher", "first-page": "1", "issue": "5", "journal-title": "PLoS Pathog", "key": "2025101516290195200_msaf211-B72", "volume": "16", "year": "2020" }, { "DOI": "10.3389/fmicb.2020.603509", "article-title": "Differential expression of viral transcripts from single-cell RNA sequencing of moderate and severe COVID-19 patients and its implications for case severity", "author": "Liu", "doi-asserted-by": "publisher", "journal-title": "Front Microbiol", "key": "2025101516290195200_msaf211-B73", "volume": "11", "year": "2020" }, { "DOI": "10.1016/j.cell.2020.06.023", "article-title": "Human virus transcriptional regulators", "author": "Liu", "doi-asserted-by": "publisher", "first-page": "24", "issue": "1", "journal-title": "Cell", "key": "2025101516290195200_msaf211-B74", "volume": "182", "year": "2020" }, { "DOI": "10.1186/1748-7188-6-26", "article-title": "ViennaRNA package 2.0", "author": "Lorenz", "doi-asserted-by": "publisher", "first-page": "26", "issue": "1", "journal-title": "Algorithms Mol Biol", "key": "2025101516290195200_msaf211-B75", "volume": "6", "year": "2011" }, { "DOI": "10.1093/hmg/ddn028", "article-title": "Deficiency of the INCL protein ppt1 results in changes in ectopic F1-ATP synthase and altered cholesterol metabolism", "author": "Lyly", "doi-asserted-by": "publisher", "first-page": "1406", "issue": "10", "journal-title": "Hum Mol Genet", "key": "2025101516290195200_msaf211-B76", "volume": "17", "year": "2008" }, { "DOI": "10.1093/nar/gkac240", "article-title": "Search and sequence analysis tools services from EMBL-EBI in 2022", "author": "Madeira", "doi-asserted-by": "publisher", "first-page": "W276", "issue": "W1", "journal-title": "Nucleic Acids Res", "key": "2025101516290195200_msaf211-B77", "volume": "50", "year": "2022" }, { "DOI": "10.1098/rsta.2020.0422", "article-title": "The simple emergence of complex molecular function", "author": "Manrubia", "doi-asserted-by": "publisher", "first-page": "20200422", "issue": "2227", "journal-title": "Philos Trans A Math Phys Eng Sci", "key": "2025101516290195200_msaf211-B78", "volume": "380", "year": "2022" }, { "DOI": "10.1038/nrg.2016.78", "article-title": "Open questions in the study of de novo genes: what, how and why", "author": "McLysaght", "doi-asserted-by": "publisher", "first-page": "567", "issue": "9", "journal-title": "Nat Rev Genet", "key": "2025101516290195200_msaf211-B79", "volume": "17", "year": "2016" }, { "DOI": "10.1073/pnas.2023157118", "article-title": "Orf10–cullin-2–zyg11b complex is not required for SARS-CoV-2 infection", "author": "Mena", "doi-asserted-by": "publisher", "first-page": "e2023157118", "issue": "17", "journal-title": "Proc Natl Acad Sci USA", "key": "2025101516290195200_msaf211-B80", "volume": "118", "year": "2021" }, { "DOI": "10.1186/1471-2229-8-99", "article-title": "Regulon organization of Arabidopsis", "author": "Mentzen", "doi-asserted-by": "publisher", "first-page": "99", "issue": "1", "journal-title": "BMC Plant Biol", "key": "2025101516290195200_msaf211-B81", "volume": "8", "year": "2008" }, { "DOI": "10.3389/fmicb.2020.01800", "article-title": "Geographic and genomic distribution of SARS-CoV-2 mutations", "author": "Mercatelli", "doi-asserted-by": "publisher", "first-page": "1800", "journal-title": "Front Microbiol", "key": "2025101516290195200_msaf211-B82", "volume": "11", "year": "2020" }, { "DOI": "10.1093/nar/gky384", "article-title": "Iupred2a: context-dependent prediction of protein disorder as a function of redox state and protein binding", "author": "Mészáros", "doi-asserted-by": "publisher", "first-page": "W329", "issue": "W1", "journal-title": "Nucleic Acids Res", "key": "2025101516290195200_msaf211-B83", "volume": "46", "year": "2018" }, { "DOI": "10.1038/s41587-022-01466-0", "article-title": "A language model beats alphafold2 on orphans", "author": "Michaud", "doi-asserted-by": "publisher", "first-page": "1576", "issue": "11", "journal-title": "Nat Biotechnol", "key": "2025101516290195200_msaf211-B84", "volume": "40", "year": "2022" }, { "DOI": "10.1093/molbev/msaa015", "article-title": "IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era", "author": "Minh", "doi-asserted-by": "publisher", "first-page": "1530", "issue": "5", "journal-title": "Mol Biol Evol", "key": "2025101516290195200_msaf211-B85", "volume": "37", "year": "2020" }, { "DOI": "10.1016/j.biopha.2021.111599", "article-title": "Novel and emerging mutations of SARS-CoV-2: biomedical implications", "author": "Mohammadi", "doi-asserted-by": "publisher", "first-page": "111599", "issue": "111599", "journal-title": "Biomed Pharmacother", "key": "2025101516290195200_msaf211-B86", "volume": "139", "year": "2021" }, { "DOI": "10.1080/22221751.2020.1870414", "article-title": "SARS-CoV-2 proteases PLpro and 3CLpro cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species", "author": "Moustaqil", "doi-asserted-by": "publisher", "first-page": "178", "issue": "1", "journal-title": "Emerg Microbes Infect", "key": "2025101516290195200_msaf211-B87", "volume": "10", "year": "2021" }, { "DOI": "10.1371/journal.pone.0249047", "article-title": "A549 cells contain enlarged mitochondria with independently functional clustered mtDNA nucleoids", "author": "Nasonovs", "doi-asserted-by": "publisher", "first-page": "e0249047", "issue": "3", "journal-title": "PLoS One", "key": "2025101516290195200_msaf211-B88", "volume": "16", "year": "2021" }, { "DOI": "10.1093/nar/gkac1072", "article-title": "The UCSC genome browser database: 2023 update", "author": "Nassar", "doi-asserted-by": "publisher", "first-page": "D1188", "issue": "D1", "journal-title": "Nucleic Acids Res", "key": "2025101516290195200_msaf211-B89", "volume": "51", "year": "2023" }, { "author": "NCBI Resource Coordinators", "key": "2025101516290195200_msaf211-B90", "volume-title": "Entrez direct: e-utilities on the UNIX command line", "year": "2010" }, { "DOI": "10.7554/eLife.59633", "article-title": "Dynamically evolving novel overlapping gene as a factor in the SARS-CoV-2 pandemic", "author": "Nelson", "doi-asserted-by": "publisher", "first-page": "e59633", "journal-title": "Elife", "key": "2025101516290195200_msaf211-B91", "volume": "9", "year": "2020" }, { "DOI": "10.1016/j.bbrc.2006.07.078", "article-title": "Aurelin, a novel antimicrobial peptide from jellyfish Aurelia aurita with structural features of defensins and channel-blocking toxins", "author": "Ovchinnikova", "doi-asserted-by": "publisher", "first-page": "514", "issue": "2", "journal-title": "Biochem Biophys Res Commun", "key": "2025101516290195200_msaf211-B92", "volume": "348", "year": "2006" }, { "DOI": "10.1371/journal.ppat.1008959", "article-title": "The SARS-CoV-2 orf10 is not essential in vitro or in vivo in humans", "author": "Pancer", "doi-asserted-by": "publisher", "first-page": "e1008959", "issue": "12", "journal-title": "PLoS Pathog", "key": "2025101516290195200_msaf211-B93", "volume": "16", "year": "2020" }, { "DOI": "10.1038/nmeth.4197", "article-title": "Salmon provides fast and bias-aware quantification of transcript expression", "author": "Patro", "doi-asserted-by": "publisher", "first-page": "417", "issue": "4", "journal-title": "Nat Methods", "key": "2025101516290195200_msaf211-B94", "volume": "14", "year": "2017" }, { "DOI": "10.1016/j.cell.2025.03.035", "article-title": "The recency and geographical origins of the bat viruses ancestral to SARS-CoV and SARS-CoV-2", "author": "Pekar", "doi-asserted-by": "publisher", "first-page": "3167", "issue": "12", "journal-title": "Cell", "key": "2025101516290195200_msaf211-B95", "volume": "188" }, { "DOI": "10.1038/s41467-024-45028-1", "article-title": "The origin and structural evolution of de novo genes in Drosophila", "author": "Peng", "doi-asserted-by": "publisher", "first-page": "810", "issue": "1", "journal-title": "Nat Commun", "key": "2025101516290195200_msaf211-B96", "volume": "15" }, { "DOI": "10.1111/pbi.2019.17.issue-1", "article-title": "QQS orphan gene and its interactor NF-YC 4 reduce susceptibility to pathogens and pests", "author": "Qi", "doi-asserted-by": "publisher", "first-page": "252", "issue": "1", "journal-title": "Plant Biotechnol J", "key": "2025101516290195200_msaf211-B97", "volume": "17", "year": "2019" }, { "DOI": "10.1073/pnas.2122897119", "article-title": "SARS-CoV-2 couples evasion of inflammatory response to activated nucleotide synthesis", "author": "Qin", "doi-asserted-by": "publisher", "first-page": "e2122897119", "issue": "26", "journal-title": "Proc Natl Acad Sci USA", "key": "2025101516290195200_msaf211-B98", "volume": "119", "year": "2022" }, { "DOI": "10.1093/bioinformatics/btq033", "article-title": "Bedtools: a flexible suite of utilities for comparing genomic features", "author": "Quinlan", "doi-asserted-by": "crossref", "first-page": "841", "issue": "6", "journal-title": "Bioinformatics.", "key": "2025101516290195200_msaf211-B142", "volume": "26", "year": "2010" }, { "DOI": "10.1007/978-3-030-41948-6_1", "author": "Ramløv", "doi-asserted-by": "publisher", "key": "2025101516290195200_msaf211-B99", "volume-title": "Antifreeze proteins volume 2: biochemistry, molecular biology and applications", "year": "2020" }, { "DOI": "10.1261/rna.076141.120", "article-title": "RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses: a first look", "author": "Rangan", "doi-asserted-by": "publisher", "first-page": "937", "issue": "8", "journal-title": "RNA", "key": "2025101516290195200_msaf211-B100", "volume": "26", "year": "2020" }, { "DOI": "10.1371/journal.pbio.3001143", "article-title": "Single-cell longitudinal analysis of SARS-CoV-2 infection in human airway epithelium identifies target cells, alterations in gene expression, and cell state changes", "author": "Ravindra", "doi-asserted-by": "publisher", "first-page": "1", "journal-title": "PLOS Biol", "key": "2025101516290195200_msaf211-B101", "volume": "19" }, { "DOI": "10.1371/journal.pgen.1003860", "article-title": "De novo ORFs in drosophila are important to organismal fitness and evolved rapidly from previously non-coding sequences", "author": "Reinhardt", "doi-asserted-by": "publisher", "first-page": "e1003860", "issue": "10", "journal-title": "PLoS Genet", "key": "2025101516290195200_msaf211-B102", "volume": "9", "year": "2013" }, { "DOI": "10.1016/s0168-95250002024-2", "article-title": "Emboss: the European molecular biology open software suite", "author": "Rice", "doi-asserted-by": "publisher", "first-page": "276", "issue": "6", "journal-title": "Trends Genet.", "key": "2025101516290195200_msaf211-B103", "volume": "16", "year": "2000" }, { "DOI": "10.1371/journal.pbio.3001091", "article-title": "A plasmid DNA-launched SARS-CoV-2 reverse genetics system and coronavirus toolkit for COVID-19 research", "author": "Rihn", "doi-asserted-by": "publisher", "first-page": "e3001091", "issue": "2", "journal-title": "PLoS Biol", "key": "2025101516290195200_msaf211-B104", "volume": "19", "year": "2021" }, { "DOI": "10.1093/bioinformatics/btaa080", "article-title": "Estimating the power of sequence covariation for detecting conserved RNA structure", "author": "Rivas", "doi-asserted-by": "publisher", "first-page": "3072", "issue": "10", "journal-title": "Bioinformatics", "key": "2025101516290195200_msaf211-B105", "volume": "36", "year": "2020" }, { "DOI": "10.1016/j.tig.2018.12.003", "article-title": "Translation of small open reading frames: roles in regulation and evolutionary innovation", "author": "Ruiz-Orera", "doi-asserted-by": "publisher", "first-page": "890", "issue": "5", "journal-title": "Trends Genet", "key": "2025101516290195200_msaf211-B106", "volume": "2", "year": "2018" }, { "DOI": "10.7554/eLife.03523", "article-title": "Long non-coding RNAS as a source of new peptides", "author": "Ruiz-Orera", "doi-asserted-by": "publisher", "first-page": "e03523", "journal-title": "eLife", "key": "2025101516290195200_msaf211-B107", "volume": "3", "year": "2014" }, { "DOI": "10.1016/j.compbiomed.2021.104703", "article-title": "An in-depth in silico and immunoinformatics approach for designing a potential multi-epitope construct for the effective development of vaccine to combat against SARS-CoV-2 encompassing variants of concern and interest", "author": "Saba", "doi-asserted-by": "publisher", "first-page": "104703", "issue": "4", "journal-title": "Comput Biol Med", "key": "2025101516290195200_msaf211-B108", "volume": "136", "year": "2021" }, { "DOI": "10.1002/yea.v37.7-8", "article-title": "Genome-wide effect of tetracycline, doxycycline and 4-epidoxycycline on gene expression in saccharomyces cerevisiae", "author": "Sanchez", "doi-asserted-by": "publisher", "first-page": "389", "issue": "7-8", "journal-title": "Yeast", "key": "2025101516290195200_msaf211-B109", "volume": "37", "year": "2020" }, { "DOI": "10.1073/pnas.2024815118", "article-title": "The total number and mass of SARS-CoV-2 virions", "author": "Sender", "doi-asserted-by": "publisher", "first-page": "e2024815118", "issue": "25", "journal-title": "Proc Natl Acad Sci USA", "key": "2025101516290195200_msaf211-B110", "volume": "118", "year": "2021" }, { "DOI": "10.1038/s41586-020-2601-5", "article-title": "Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity", "author": "Shin", "doi-asserted-by": "publisher", "first-page": "657", "issue": "7835", "journal-title": "Nature", "key": "2025101516290195200_msaf211-B111", "volume": "587", "year": "2020" }, { "DOI": "10.2807/1560-7917.ES.2017.22.13.30494", "article-title": "GISAID: global initiative on sharing all influenza data - from vision to reality", "author": "Shu", "doi-asserted-by": "publisher", "issue": "13", "journal-title": "Euro Surveill", "key": "2025101516290195200_msaf211-B112", "volume": "22", "year": "2017" }, { "DOI": "10.1038/s12276-021-00604-z", "article-title": "On the origin and evolution of SARS-CoV-2", "author": "Singh", "doi-asserted-by": "publisher", "first-page": "537", "issue": "4", "journal-title": "Exp Mol Med", "key": "2025101516290195200_msaf211-B113", "volume": "53", "year": "2021" }, { "DOI": "10.1101/2024.02.21.581488", "author": "Singh", "doi-asserted-by": "publisher", "key": "2025101516290195200_msaf211-B114" }, { "DOI": "10.1093/nargab/lqab049", "article-title": "pyrpipe: a Python package for RNA-Seq workflows", "author": "Singh", "doi-asserted-by": "publisher", "first-page": "lqab049", "issue": "2", "journal-title": "NAR Genom Bioinform", "key": "2025101516290195200_msaf211-B115", "volume": "3", "year": "2021" }, { "DOI": "10.7554/eLife.55136", "article-title": "Genetic novelty: how new genes are born", "author": "Singh", "doi-asserted-by": "publisher", "first-page": "e55136", "journal-title": "eLife", "key": "2025101516290195200_msaf211-B116", "volume": "9", "year": "2020" }, { "DOI": "10.1186/s13072-022-00454-7", "article-title": "Viral histones: pickpocket’s prize or primordial progenitor?", "author": "Talbert", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Epigenetics Chromatin", "key": "2025101516290195200_msaf211-B117", "volume": "15", "year": "2022" }, { "DOI": "10.1038/nrg3053", "article-title": "The evolutionary origin of orphan genes", "author": "Tautz", "doi-asserted-by": "publisher", "first-page": "692", "issue": "10", "journal-title": "Nat Rev Genet", "key": "2025101516290195200_msaf211-B118", "volume": "12", "year": "2011" }, { "DOI": "10.1093/bib/bbs017", "article-title": "Integrative genomics viewer (IGV): high-performance genomics data visualization and exploration", "author": "Thorvaldsdottir", "doi-asserted-by": "publisher", "first-page": "178", "issue": "2", "journal-title": "Brief Bioinform", "key": "2025101516290195200_msaf211-B119", "volume": "14", "year": "2013" }, { "DOI": "10.1073/pnas.2401968121", "article-title": "Lethal COVID-19 associates with RAAS-induced inflammation for multiple organ damage including mediastinal lymph nodes", "author": "Topper", "doi-asserted-by": "publisher", "first-page": "e2401968121", "issue": "49", "journal-title": "Proc Natl Acad Sci USA", "key": "2025101516290195200_msaf211-B120", "volume": "121", "year": "2024" }, { "DOI": "10.1101/gr.278977.124", "article-title": "Large-scale investigation of species-specific orphan genes in the human gut microbiome elucidates their evolutionary origins", "author": "Vakirlis", "doi-asserted-by": "publisher", "first-page": "888", "issue": "6", "journal-title": "Genome Res", "key": "2025101516290195200_msaf211-B121", "volume": "34", "year": "2024" }, { "DOI": "10.1137/040608635", "article-title": "Graph clustering via a discrete uncoupling process", "author": "Van Dongen", "doi-asserted-by": "publisher", "first-page": "121", "issue": "1", "journal-title": "SIAM J Matrix Anal Appl", "key": "2025101516290195200_msaf211-B122", "volume": "30", "year": "2008" }, { "DOI": "10.1371/journal.pgen.1008160", "article-title": "De novo gene birth", "author": "Van Oss", "doi-asserted-by": "publisher", "first-page": "e1008160", "issue": "5", "journal-title": "PLoS Genet", "key": "2025101516290195200_msaf211-B123", "volume": "15", "year": "2019" }, { "DOI": "10.1371/journal.ppat.1011471", "article-title": "To eat or not to eat mitochondria? How do host cells cope with mitophagy upon bacterial infection?", "author": "Verbeke", "doi-asserted-by": "publisher", "first-page": "e1011471", "issue": "7", "journal-title": "PLoS Pathog", "key": "2025101516290195200_msaf211-B124", "volume": "19", "year": "2023" }, { "DOI": "10.1038/nrc3365", "article-title": "Mitochondria and cancer", "author": "Wallace", "doi-asserted-by": "publisher", "first-page": "685", "issue": "10", "journal-title": "Nat Rev Cancer", "key": "2025101516290195200_msaf211-B125", "volume": "12", "year": "2012" }, { "DOI": "10.1083/jcb.202108015", "article-title": "SARS-CoV-2 orf10 impairs cilia by enhancing cul2zyg11b activity", "author": "Wang", "doi-asserted-by": "publisher", "first-page": "e202108015", "issue": "7", "journal-title": "J Cell Biol", "key": "2025101516290195200_msaf211-B126", "volume": "221", "year": "2022" }, { "DOI": "10.1038/s41577-021-00656-2", "article-title": "Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses—are we our own worst enemy?", "author": "Wong", "doi-asserted-by": "publisher", "first-page": "47", "issue": "1", "journal-title": "Nat Rev Immunol", "key": "2025101516290195200_msaf211-B127", "volume": "22", "year": "2022" }, { "DOI": "10.7554/eLife.42940", "article-title": "eIF2B activator prevents neurological defects caused by a chronic integrated stress response", "author": "Wong", "doi-asserted-by": "publisher", "journal-title": "eLife", "key": "2025101516290195200_msaf211-B128", "volume": "8", "year": "2019" }, { "DOI": "10.7554/eLife.32733", "article-title": "The small molecule ISRIB rescues the stability and activity of vanishing white matter disease eIF2B mutant complexes", "author": "Wong", "doi-asserted-by": "publisher", "journal-title": "eLife", "key": "2025101516290195200_msaf211-B129", "volume": "7", "year": "2018" }, { "DOI": "10.1016/j.celrep.2021.108761", "article-title": "SARS-CoV-2 ORF9b inhibits RIG-I-MAVS antiviral signaling by interrupting k63-linked ubiquitination of NEMO", "author": "Wu", "doi-asserted-by": "publisher", "first-page": "108761", "issue": "7", "journal-title": "Cell Rep", "key": "2025101516290195200_msaf211-B130", "volume": "34", "year": "2021" }, { "DOI": "10.1016/j.xinn.2021.100141", "article-title": "clusterProfiler 4.0: a universal enrichment tool for interpreting omics data", "author": "Wu", "doi-asserted-by": "publisher", "first-page": "100141", "issue": "3", "journal-title": "Innovation (Camb)", "key": "2025101516290195200_msaf211-B131", "volume": "2", "year": "2021" }, { "DOI": "10.1016/j.celrep.2020.108234", "article-title": "Evasion of type I interferon by SARS-CoV-2", "author": "Xia", "doi-asserted-by": "publisher", "first-page": "108234", "issue": "1", "journal-title": "Cell Rep", "key": "2025101516290195200_msaf211-B132", "volume": "33", "year": "2020" }, { "DOI": "10.1038/s12276-021-00658-z", "article-title": "Mutational spectrum of SARS-CoV-2 during the global pandemic", "author": "Yi", "doi-asserted-by": "publisher", "first-page": "1229", "issue": "8", "journal-title": "Exp Mol Med", "key": "2025101516290195200_msaf211-B133", "volume": "53", "year": "2021" }, { "DOI": "10.1186/1471-2164-9-1", "article-title": "Identification and investigation of ORFans in the viral world", "author": "Yin", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "BMC Genomics", "key": "2025101516290195200_msaf211-B134", "volume": "9", "year": "2008" }, { "DOI": "10.1111/mee3.2017.8.issue-1", "article-title": "ggtree: an R package for visualization and annotation of phylogenetic trees with their covariates and other associated data", "author": "Yu", "doi-asserted-by": "publisher", "first-page": "28", "issue": "1", "journal-title": "Methods Ecol Evol", "key": "2025101516290195200_msaf211-B135", "volume": "8", "year": "2017" }, { "DOI": "10.1038/s41577-022-00715-2", "article-title": "Orf9c and orf10 as accessory proteins of SARS-CoV-2 in immune evasion", "author": "Zandi", "doi-asserted-by": "publisher", "first-page": "331", "issue": "5", "journal-title": "Nat Rev Immunol", "key": "2025101516290195200_msaf211-B136", "volume": "22", "year": "2022" }, { "DOI": "10.1016/j.bbrc.2022.05.069", "article-title": "Structural insights into ORF10 recognition by ZYG11B", "author": "Zhang", "doi-asserted-by": "publisher", "first-page": "14", "journal-title": "Biochem Biophys Res Commun", "key": "2025101516290195200_msaf211-B137", "volume": "616", "year": "2022" }, { "DOI": "10.1038/s41392-024-02041-6", "article-title": "A systemic and molecular study of subcellular localization of SARS-CoV-2 proteins", "author": "Zhang", "doi-asserted-by": "publisher", "first-page": "1", "issue": "1", "journal-title": "Signal Transduct Target Ther", "key": "2025101516290195200_msaf211-B138", "volume": "5", "year": "2020" }, { "DOI": "10.1101/2021.07.17.452750", "author": "Zhao", "doi-asserted-by": "publisher", "key": "2025101516290195200_msaf211-B139" }, { "DOI": "10.1186/s13578-021-00569-6", "article-title": "Neddylation regulation of mitochondrial structure and functions", "author": "Zhou", "doi-asserted-by": "publisher", "first-page": "55", "issue": "1", "journal-title": "Cell Biosci", "key": "2025101516290195200_msaf211-B140", "volume": "11", "year": "2021" }, { "DOI": "10.1186/s13059-022-02696-w", "article-title": "Gene fusion as an important mechanism to generate new genes in the genus Oryza", "author": "Zhou", "doi-asserted-by": "publisher", "first-page": "130", "issue": "1", "journal-title": "Genome Biol", "key": "2025101516290195200_msaf211-B141", "volume": "23", "year": "2022" } ], "reference-count": 142, "references-count": 142, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/mbe/article/doi/10.1093/molbev/msaf211/8287009" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis", "type": "journal-article", "volume": "42" }
Please send us corrections, updates, or comments. c19early involves the extraction of 200,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. IMA and WCH provide treatment protocols.
  or use drag and drop   
Submit    
Post
Share
@CovidAnalysis
FAQ
Public domain CC0 1.0