A Random Effects Branch-Site Model for Detecting Episodic Diversifying Selection

Pond, Sergei L. Kosakovsky; Murrell, Ben; Fourment, Mathieu; Frost, Simon D. W.; Delport, Wayne; Scheffler, Konrad

doi:10.1093/molbev/msr125

Cited by 376 publications

(317 citation statements)

References 36 publications

(65 reference statements)

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“…The methods used to investigate positive codon sites included FEL, SLAC, FUBAR, MEME,62, 63, 64 the branch site REL and the GA‐branch site models were chosen to determine the selection pressure on the individual branches 65, 66. Methods with p < 0.1 in SLAC, p < 0.05 in FEL and MEME and the posterior probability >0.9 in FUBAR, were considered to be more conservative positive selection pressure.…”

Section: Methodsmentioning

confidence: 99%

Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3

et al. 2018

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Porcine circovirus 3 (PCV3) is a novel virus associated with acute PDNS (porcine dermatitis and nephropathy syndrome)‐like clinical signs identified by metagenomic sequencing from swine. Its high occurrence may pose a potential threat to the swine industry worldwide. The processes resulting in the emergence and spread of PCV3 remain poorly understood. Herein, the possible origin, genotypes, and evolutionary dynamics of PCV3 based on available genomic sequences are determined. The closest ancestor of PCV3 is found to be within the clade 1 bat CVs. Using different phylogenetic methods, two major genotypes are identified, PCV3a and PCV3b. It is found that the effective population size of PCV3 increased rapidly during late 2013 to early 2014 and this is associated with the diversification of PCV3a and PCV3b. A relatively high effective reproductive number (Re) value and higher evolutionary rate were found compared to other single‐stranded DNA viruses, and positive selection on codons 122 and 320 (24 of ORF2) is identified. It is hypothesized that this, together with the prediction of a potential change of an antigenic epitope at position 320, might have allowed PCV3 to escape from the host immune response. Overall, this study has important implications for understanding the ongoing PCV3 cases worldwide and will guide future efforts to develop effective preventive and control measures.

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Section: Methodsmentioning

confidence: 99%

Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3

et al. 2018

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“…To determine whether any codons across the WNV genome may have been subject to adaptive evolution, manifest as a greater number of nonsynonymous (dN) than synonymous (dS) substitutions per site, we used the SLAC (single-likelihood ancestor counting), FUBAR (fast unbiased Bayesian approximation), and MEME (mixed effects model of evolution) methods (41)(42)(43) available in the HyPhy package, utilizing the GTR substitution model and the ML tree inferred for the full data set of 696 sequences. To determine whether there are instances of positive selection of individual branches of the WNV phylogeny, we employed the branch-site REL method (44) in HyPhy. In addition, we estimated the ratio of nonsynonymous to synonymous substitutions per site (dN/dS) on internal and external branches separately, using PAML (45), in which an excess of nonsynonymous substitutions on internal branches is compatible with adaptive evolution.…”

Section: Methodsmentioning

confidence: 99%

Fluid Spatial Dynamics of West Nile Virus in the United States: Rapid Spread in a Permissive Host Environment

Giallonardo

Geoghegan

Docherty

et al. 2016

J Virol

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The introduction of West Nile virus (WNV) into North America in 1999 is a classic example of viral emergence in a new environment, with its subsequent dispersion across the continent having a major impact on local bird populations. Despite the importance of this epizootic, the pattern, dynamics, and determinants of WNV spread in its natural hosts remain uncertain. In particular, it is unclear whether the virus encountered major barriers to transmission, or spread in an unconstrained manner, and if specific viral lineages were favored over others indicative of intrinsic differences in fitness. To address these key questions in WNV evolution and ecology, we sequenced the complete genomes of approximately 300 avian isolates sampled across the United States between 2001 and 2012. Phylogenetic analysis revealed a relatively star-like tree structure, indicative of explosive viral spread in the United States, although with some replacement of viral genotypes through time. These data are striking in that viral sequences exhibit relatively limited clustering according to geographic region, particularly for those viruses sampled from birds, and no strong phylogenetic association with well-sampled avian species. The genome sequence data analyzed here also contain relatively little evidence for adaptive evolution, particularly of structural proteins, suggesting that most viral lineages are of similar fitness and that WNV is well adapted to the ecology of mosquito vectors and diverse avian hosts in the United States. In sum, the molecular evolution of WNV in North America depicts a largely unfettered expansion within a permissive host and geographic population with little evidence of major adaptive barriers. IMPORTANCE How viruses spread in new host

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“…Codons subject to episodic diversifying selection were identified with the mixed-effects model of evolution (MEME) method (37). Codons with P values of Ͻ0.05 were reported as positively selected codons.…”

Section: Viruses a Total Of 284 A(h3n2) Viruses Isolated Between 196mentioning

confidence: 99%

Genomewide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011

Westgeest¹,

Russell

Lin

et al. 2014

J Virol

143

122

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Influenza A(H3N2) viruses became widespread in humans during the 1968 H3N2 virus pandemic and have been a major cause of influenza epidemics ever since. These viruses evolve continuously by reassortment and genomic evolution. Antigenic drift is the cause for the need to update influenza vaccines frequently. Using two data sets that span the entire period of circulation of human influenza A(H3N2) viruses, it was shown that influenza A(H3N2) virus evolution can be mapped to 13 antigenic clusters. Here we analyzed the full genomes of 286 influenza A(H3N2) viruses from these two data sets to investigate the genomic evolution and reassortment patterns. Numerous reassortment events were found, scattered over the entire period of virus circulation, but most prominently in viruses circulating between 1991 and 1998. Some of these reassortment events persisted over time, and one of these coincided with an antigenic cluster transition. Furthermore, selection pressures and nucleotide and amino acid substitution rates of all proteins were studied, including those of the recently discovered PB1-N40, PA-X, PA-N155, and PA-N182 proteins. Rates of nucleotide and amino acid substitutions were most pronounced for the hemagglutinin, neuraminidase, and PB1-F2 proteins. Selection pressures were highest in hemagglutinin, neuraminidase, matrix 1, and nonstructural protein 1. This study of genotype in relation to antigenic phenotype throughout the period of circulation of human influenza A(H3N2) viruses leads to a better understanding of the evolution of these viruses. IMPORTANCEEach winter, influenza virus infects approximately 5 to 15% of the world's population, resulting in significant morbidity and mortality. Influenza A(H3N2) viruses evolve continuously by reassortment and genomic evolution. This leads to changes in antigenic recognition (antigenic drift) which make it necessary to update vaccines against influenza A(H3N2) viruses frequently. In this study, the relationship of genetic evolution to antigenic change spanning the entire period of A(H3N2) virus circulation was studied for the first time. The results presented in this study contribute to a better understanding of genetic evolution in correlation with antigenic evolution of influenza A(H3N2) viruses.

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A Random Effects Branch-Site Model for Detecting Episodic Diversifying Selection

Cited by 376 publications

References 36 publications

Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3

Origin, Genetic Diversity, and Evolutionary Dynamics of Novel Porcine Circovirus 3

Fluid Spatial Dynamics of West Nile Virus in the United States: Rapid Spread in a Permissive Host Environment

Genomewide Analysis of Reassortment and Evolution of Human Influenza A(H3N2) Viruses Circulating between 1968 and 2011

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