11eedfe7b0b96d44ccf865546ea1b16d Vir_a2020v12n11p1305.pdf 11f02dbe1a3422dcecb73dc2803965f19b4cd906 Vir_a2020v12n11p1305.pdf 3a60efe84117b0c762f417e5587518f571308c9597fba8075aac0553b257e550 Vir_a2020v12n11p1305.pdf Title: Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections Subject: Newcastle disease virus (NDV) infections are well known to harbour quasispecies, due to the error-prone nature of the RNA polymerase. Quasispecies variants in the fusion cleavage site of the virus are known to significantly change its virulence. However, little is known about the genomic patterns of diversity and selection in NDV viral swarms. We analyse deep sequencing data from in vitro and in vivo NDV infections to uncover the genomic patterns of diversity and the signatures of selection within NDV swarms. Variants in viruses from in vitro samples are mostly localised in non-coding regions and 3' and 5' untranslated regions (3'UTRs or 5'UTRs), while in vivo samples contain an order of magnitude more variants. We find different patterns of genomic divergence and diversity among NDV genotypes, as well as differences in the genomic distribution of intra-host variants among in vitro and in vivo infections of the same strain. The frequency spectrum shows clear signatures of intra-host purifying selection in vivo on the matrix protein (M) coding gene and positive or diversifying selection on nucleocapsid (NP) and haemagglutinin-neuraminidase (HN). The comparison between within-host polymorphisms and phylogenetic divergence reveals complex patterns of selective pressure on the NDV genome at between- and within-host level. The M sequence is strongly constrained both between and within hosts, fusion protein (F) coding gene is under intra-host positive selection, and NP and HN show contrasting patterns: HN RNA sequence is positively selected between hosts while its protein sequence is positively selected within hosts, and NP is under intra-host positive selection at the RNA level and negative selection at the protein level. Keywords: Newcastle disease virus; deep sequencing; intra-host variability; quasispecies; genetic diversity; genetic variability; Tajima’s D; McDonald–Kreitman test Author: Archana Jadhav, Lele Zhao, Weiwei Liu, Chan Ding, Venugopal Nair, Sebastian E. 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1.12.1 (2019-04-17) LastModified: 2021-02-25 19:59:50 CET Size: 2315720 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 568 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Cell Culture Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: RNA Extraction and Sequencing Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: In Vivo Studies Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Bioinformatic Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Samples and Read Depth Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Overall Genetic Diversity Show Higher Diversity in the In Vivo Samples Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: An Excess of Low-Frequency Variants is Compatible with an Exponential Growth Rate within Host/Culture Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Genetic Diversity along the Genome Shows Regions of High Diversity and/or Hypermutability Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: The Site Frequency Spectrum (SFS) Gives Clues about Evolutionary Events Occurring within Host Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Looking for Signatures of Selection: Non-Synonymous, Synonymous and Non-Coding Variants Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Children: Item: Title: Ratios of Polymorphism within-Host at Functional Versus Non-Functional Positions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: The Patterns of Polymorphism within-Host Versus the Divergence between-Host Are not Always Correlated Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: Contrasting the Patterns of Polymorphism within-Host Versus the Divergence between-Host at Functional Versus Non-Functional Positions: Differential Selective Patterns at Different Stages Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@6121c9d6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@87f383f Info: Title: Genomic Diversity and Evolution of Quasispecies in Newcastle Disease Virus Infections Author: Archana Jadhav, Lele Zhao, Weiwei Liu, Chan Ding, Venugopal Nair, Sebastian E. Ramos-Onsins and Luca Ferretti Subject: Newcastle disease virus (NDV) infections are well known to harbour quasispecies, due to the error-prone nature of the RNA polymerase. Quasispecies variants in the fusion cleavage site of the virus are known to significantly change its virulence. However, little is known about the genomic patterns of diversity and selection in NDV viral swarms. We analyse deep sequencing data from in vitro and in vivo NDV infections to uncover the genomic patterns of diversity and the signatures of selection within NDV swarms. Variants in viruses from in vitro samples are mostly localised in non-coding regions and 3' and 5' untranslated regions (3'UTRs or 5'UTRs), while in vivo samples contain an order of magnitude more variants. We find different patterns of genomic divergence and diversity among NDV genotypes, as well as differences in the genomic distribution of intra-host variants among in vitro and in vivo infections of the same strain. The frequency spectrum shows clear signatures of intra-host purifying selection in vivo on the matrix protein (M) coding gene and positive or diversifying selection on nucleocapsid (NP) and haemagglutinin-neuraminidase (HN). The comparison between within-host polymorphisms and phylogenetic divergence reveals complex patterns of selective pressure on the NDV genome at between- and within-host level. The M sequence is strongly constrained both between and within hosts, fusion protein (F) coding gene is under intra-host positive selection, and NP and HN show contrasting patterns: HN RNA sequence is positively selected between hosts while its protein sequence is positively selected within hosts, and NP is under intra-host positive selection at the RNA level and negative selection at the protein level. 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367, 585, 404, 596 Annotation: Subtype: Link Rect: 100, 560, 137, 570 Annotation: Subtype: Link Rect: 375, 533, 412, 544 Annotation: Subtype: Link Rect: 463, 508, 501, 519 Annotation: Subtype: Link Rect: 145, 470, 183, 480 Annotation: Subtype: Link Rect: 433, 443, 470, 454 Annotation: Subtype: Link Rect: 291, 405, 328, 415 Annotation: Subtype: Link Rect: 334, 405, 370, 415 Annotation: Subtype: Link Rect: 355, 379, 392, 389 Annotation: Subtype: Link Rect: 373, 353, 410, 364 Annotation: Subtype: Link Rect: 416, 353, 453, 364 Annotation: Subtype: Link Rect: 145, 315, 183, 325 Annotation: Subtype: Link Rect: 380, 275, 417, 286 Annotation: Subtype: Link Rect: 327, 236, 365, 247 Annotation: Subtype: Link Rect: 145, 199, 183, 209 Annotation: Subtype: Link Rect: 333, 159, 371, 170 Annotation: Subtype: Link Rect: 76, 87, 166, 118 Annotation: Subtype: Link Rect: 234, 81, 407, 92 Checksum: 37f7cf44 Type: CRC32 Checksum: 11eedfe7b0b96d44ccf865546ea1b16d Type: MD5 Checksum: 11f02dbe1a3422dcecb73dc2803965f19b4cd906 Type: SHA-1