DOI: 10.5061/dryad.v8j2vk5
title: Data from: Hepatitis C virus genotype 1 and 2 recombinant genomes and the phylogeographic history of the 2k/1b lineage

description: Recombination is an important driver of genetic diversity, though it is
 relatively uncommon in hepatitis C virus (HCV). Recent investigation of
 sequence data acquired from HCV clinical trials produced 21 full-genome
 recombinant viruses belonging to three putative inter-subtype forms 2b/1a,
 2b/1b, and 2k/1b. The 2k/1b chimera is the only known HCV circulating
 recombinant form (CRF), provoking interest in its genetic structure and
 origin. Discovered in Russia in 1999, 2k/1b cases have since been detected
 throughout the former Soviet Union, Western Europe, and North America.
 Although 2k/1b prevalence is highest in the Caucasus mountain region
 (i.e., Armenia, Azerbaijan, and Georgia), the origin and migration
 patterns of CRF 2k/1b have remained obscure due to a paucity of available
 sequences. We assembled an alignment which spans the entire coding region
 of the HCV genome containing all available 2k/1b sequences (&gt;500
 nucleotides; n=109) sampled in 19 countries from public databases (102
 individuals), additional newly sequenced genomic regions (from 48 of these
 102 individuals), unpublished isolates with newly sequenced regions (5
 additional individuals), and novel complete genomes (2 additional
 individuals) generated in this study. Analysis of this expanded dataset
 reconfirmed the monophyletic origin of 2k/1b with a recombination
 breakpoint at position 3,187 (95% confidence interval: 3,172–3,202; HCV
 GT1a reference strain H77). Phylogeography is a valuable tool used to
 reveal viral migration dynamics. Inference of the timed history of spread
 in a Bayesian framework identified Russia as the ancestral source of the
 CRF 2k/1b clade. Further, we found evidence for migration routes leading
 out of Russia to other former Soviet Republics or countries under the
 Soviet sphere of influence. These findings suggest an interplay between
 geopolitics and the historical spread of CRF 2k/1b.
description: 2k/1b full coding region
 sequence alignmentContains 109 sequences
 of Hepatitis C virus circulating recombinant form 2k/1b spanning the
 entire coding region. Aligned with MUSCLE v2.0 in AliView and edited
 manually.2k1b_109_fullCodingRegion.fasta2k/1b densely sampled coding region sequence alignmentContains 109 sequences of Hepatitis C virus circulating recombinant form 2k/1b spanning the most densely sampled coding regions (i.e. at least 25 sequences in that region): Core/E1, NS2/NS3, NS4B, NS5A/NS5B, all concatenated. Aligned with MUSCLE v2.0 in AliView and edited manually.2k1b_109_denselySampled_concatenatedCoreE1NS23NS4BNS5AB.fastaCaucasus sensitivity analysis MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic Caucasus sensitivity analysis. The Caucasus mountain countries Armenia, Azerbaijan, and Georgia are combined into a single geographic location.2k1b_FullCOO_Caucasus11.MCC.tree2k/1b dense genome 1 GTRΓ4, 1 clock country of origin MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic analysis. Performed on posterior distribution of trees from densely sampled genome analysis with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.2k1b_denseGenome_1GTR1clock_COO_BSSVSMJ.MCC.tree2k/1b dense genome 4 GTRΓ4, 1 clock country of origin MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic analysis. Performed on posterior distribution of trees from densely sampled genome analysis with four partitioned GTRΓ4 substitution models and a single uncorrelated relaxed lognormal clock.2k1b_denseGenome_4GTR1clock_COO_BSSVSMJ.MCC.tree2k/1b dense genome 4 GTRΓ4, 4 clock country of origin MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic analysis. Performed on posterior distribution of trees from densely sampled genome analysis with four partitioned GTRΓ4 substitution models and four uncorrelated relaxed lognormal clocks.2k1b_denseGenome_4GTR4clocks_COO_BSSVSMJ.MCC.tree2k/1b full genome 1 GTRΓ4, 1 clock country of origin MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic analysis. Performed on posterior distribution of trees from full coding region analysis with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.2k1b_fullGenome_1GTR1clock_COO_BSSVSMJ.MCC.tree2k/1b full genome 9 GTRΓ4, 1 clock country of origin MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic analysis. Performed on posterior distribution of trees from full coding region analysis with nine partitioned GTRΓ4 substitution models and a single uncorrelated relaxed lognormal clock.2k1b_fullGenome_9GTR1clock_COO_BSSVSMJ.MCC.tree2k/1b full genome 9 GTRΓ4, 9 clock country of origin MCC treeMaximum clade credibility (MCC) tree from country of origin phylogeographic analysis. Performed on posterior distribution of trees from full coding region analysis with nine partitioned GTRΓ4 substitution models and nine uncorrelated relaxed lognormal clocks.2k1b_fullGenome_9GTR9clocks_COO_BSSVSMJ.MCC.treeAlignment containing HCV 1a full genomes and recombinant 2b/1a hemigenomesAll publicly available HCV 1a sequences were downloaded from GenBank and the Los Alamos National Laboratories (LANL). These were aligned with 2b/1a hemigenomes, representing the 1a portion of the coding region separated at the Recombination Detection Program (RDP)-inferred breakpoint, using the fast option in MAFFT version 7 in AliView and edited manually. Recombinant genomes were acquired from this study or these databases.2b1a_1a_ext.fastaAlignment containing HCV 2b full genomes and recombinant 2b/1a hemigenomesAll publicly available HCV 2b sequences were downloaded from GenBank and the Los Alamos National Laboratories (LANL). These were aligned with 2b/1a hemigenomes, representing the 2b portion of the coding region separated at the Recombination Detection Program (RDP)-inferred breakpoint, using the fast option in MAFFT version 7 in AliView and edited manually. Recombinant genomes were acquired from this study or these databases.2b1a_2b_ext.fastaAlignment containing HCV 1b full genomes and recombinant 2b/1b hemigenomesAll publicly available HCV 1b sequences were downloaded from GenBank and the Los Alamos National Laboratories (LANL). These were aligned with 2b/1b hemigenomes, representing the 1b portion of the coding region separated at the Recombination Detection Program (RDP)-inferred breakpoint, using the fast option in MAFFT version 7 in AliView and edited manually. Recombinant genomes were acquired from this study or these databases.2b1b_1b_ext.fastaAlignment containing HCV 2b full genomes and recombinant 2b/1b hemigenomesAll publicly available HCV 2b sequences were downloaded from GenBank and the Los Alamos National Laboratories (LANL). These were aligned with 2b/1b hemigenomes, representing the 2b portion of the coding region separated at the Recombination Detection Program (RDP)-inferred breakpoint, using the fast option in MAFFT version 7 in AliView and edited manually. Recombinant genomes were acquired from this study or these databases.2b1b_2b_ext.fastaAlignment containing HCV 1b full genomes and recombinant 2k/1b hemigenomesAll publicly available HCV 1b sequences were downloaded from GenBank and the Los Alamos National Laboratories (LANL). These were aligned with 2k/1b hemigenomes, representing the 1b portion of the coding region separated at the Recombination Detection Program (RDP)-inferred breakpoint, using the fast option in MAFFT version 7 in AliView and edited manually. Recombinant genomes were acquired from this study or these databases.2k1b_1b_ext.fastaAlignment containing HCV 2k full genomes and recombinant 2k/1b hemigenomesAll publicly available HCV 2k sequences were downloaded from GenBank and the Los Alamos National Laboratories (LANL). These were aligned with 2k/1b hemigenomes, representing the 2k portion of the coding region separated at the Recombination Detection Program (RDP)-inferred breakpoint, using the fast option in MAFFT version 7 in AliView and edited manually. Recombinant genomes were acquired from this study or these databases.2k1b_2k_ext.fasta2b/1a and 1a IQ-TreeMidpoint-rooted maximum likelihood (ML) phylogeny produced in IQ-Tree from fasta file containing all publicly available HCV 1a sequences and recombinant 2b/1a hemigenomes. All non-recombinant clades comprising 4 or more taxa are collapsed. Bootstrap support available as node labels.2b1a_1a_ext_IQTree_midpoint.tre2b/1a, 2b/1b and 2b IQ-TreeMidpoint-rooted maximum likelihood (ML) phylogeny produced in IQ-Tree from fasta file containing all publicly available HCV 2b sequences and recombinant 2b/1a and 2b/1b hemigenomes. All non-recombinant clades comprising 4 or more taxa are collapsed. Bootstrap support available as node labels.2b1a-2b1b_2b_IQTree_midpoint.tre2k/1b and 2k IQ-TreeMidpoint-rooted maximum likelihood (ML) phylogeny produced in IQ-Tree from fasta file containing all publicly available HCV 2k sequences and recombinant 2k/1b hemigenomes. All non-recombinant clades comprising 4 or more taxa are collapsed. Bootstrap support available as node labels.2k1b_2k_ext_IQTree_midpoint.tre2k/1b, 2b/1b and 1b IQ-TreeMidpoint-rooted maximum likelihood (ML) phylogeny produced in IQ-Tree from fasta file containing all publicly available HCV 1b sequences and recombinant 2k/1b and 2b/1b hemigenomes. All non-recombinant clades comprising 4 or more taxa are collapsed. Bootstrap support available as node labels.2k1b-2b1b_1b_IQTree_midpoint.tre2k/1b Caucasus sensitivity analysis country of origin XMLXML for BEAST analysis on 2k/1b country of origin containing Armenia, Azerbaijan, and Georgia as a single geographic location. Performed on posterior distribution of trees from full coding region analysis with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.2k1b_FullCOO_Caucasus11.xml2k/1b dense genome 1 GTRΓ4, 1 clock country of origin XMLXML for BEAST analysis on 2k/1b country of origin on posterior distribution of trees from densely sampled region analysis with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.2k1b_denseGenome_1GTR1clock_COO_BSSVS_MarkovJumps.xml2k/1b dense genome 4 GTRΓ4, 1 clock country of origin XMLXML for BEAST analysis on 2k/1b country of origin on posterior distribution of trees from densely sampled region analysis with four partitioned GTRΓ4 substitution models and a single uncorrelated relaxed lognormal clock.2k1b_denseGenome_4GTR1clock_COO_BSSVS_MarkovJumps.xml2k/1b dense genome 4 GTRΓ4, 4 clocks country of origin XMLXML for BEAST analysis on 2k/1b country of origin on posterior distribution of trees from densely sampled region analysis with four partitioned GTRΓ4 substitution models and four uncorrelated relaxed lognormal clocks.2k1b_denseGenome_4GTR4clocks_COO_BSSVS_MarkovJumps.xml2k/1b full genome 1 GTRΓ4, 1 clock country of origin XMLXML for BEAST analysis on 2k/1b country of origin on posterior distribution of trees from full coding region analysis with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.2k1b_fullGenome_1GTR1clock_COO_BSSVS_MarkovJumps.xml2k/1b full genome 9 GTRΓ4, 1 clock country of origin XMLXML for BEAST analysis on 2k/1b country of origin on posterior distribution of trees from full coding region analysis with nine partitioned GTRΓ4 substitution models and a single uncorrelated relaxed lognormal clock.2k1b_fullGenome_9GTR1clock_COO_BSSVS_MarkovJumps.xml2k/1b full genome 9 GTRΓ4, 9 clocks country of origin XMLXML for BEAST analysis on 2k/1b country of origin on posterior distribution of trees from full coding region analysis with nine partitioned GTRΓ4 substitution models and nine uncorrelated relaxed lognormal clocks.2k1b_fullGenome_9GTR9clocks_COO_BSSVS_MarkovJumps.xml2k/1b full coding region 9 GTRΓ4, 1 clock XMLXML for BEAST analysis on HCV 2k/1b full coding region with nine GTRΓ4 substitution models and a single uncorrelated relaxed lognormal clock.2k1b_FullGenome_9GTR1clock.xml2k/1b full coding region 9 GTRΓ4, 9 clock XMLXML for BEAST analysis on HCV 2k/1b full coding region with nine GTRΓ4 substitution models and nine uncorrelated relaxed lognormal clocks.2k1b_FullGenome_9GTR9clocks.xml2k/1b full coding region 1 GTRΓ4, 1 clock XMLXML for BEAST analysis on HCV 2k/1b full coding region with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.2k1b_Genome_skyride_109.xml2k/1b densely sampled coding region 4 GTRΓ4, 1 clock XMLXML for BEAST analysis on HCV 2k/1b densely sampled coding region with four GTRΓ4 substitution models and a single uncorrelated relaxed lognormal clock.Skyride_denselySampled_4GTR1clock.xml2k/1b densely sampled coding region 4 GTRΓ4, 4 clock XMLXML for BEAST analysis on HCV 2k/1b densely sampled coding region with four GTRΓ4 substitution models and four uncorrelated relaxed lognormal clocks.Skyride_denselySampled_4GTR4clocks.xml2k/1b densely sampled coding region 1 GTRΓ4, 1 clock XMLXML for BEAST analysis on HCV 2k/1b densely sampled coding region with a single GTRΓ4 substitution model and a single uncorrelated relaxed lognormal clock.Skyride_denselySampled_concatenatedCoreE1NS23NS4BNS5AB.xml