Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene

Kok Keng Tee, Tommy Tsan‐Yuk Lam, Yoke Fun Chan, Jon M. Bible, Adeeba Kamarulzaman, C. Y. William Tong, Yutaka Takebe, Oliver G. Pybus · Journal of Virology · 2010 · evolutionary-virology · 10.1128/jvi.01019-09 · record tee2010-evolutionary-genetics-of-human-ent
tag layer · index · concepts · authors · עברית

Where this record's text came from. faceted 2026-08 by reading the locally held text (html); every evidence string verified as an exact substring of that text before merging. The extraction is a PMC page: the long author/affiliation block and the site chrome sit below the ARTICLE TEXT marker, so quoting was restricted to the abstract, body and discussion. Spacing inside citation and figure references is an artefact of the HTML-to-text conversion ('( 73 )', '( n = 628)') and has been preserved verbatim in the quotes. The two claim relations cite prior work by reference number rather than by author name, but the relational language ('less statistically appropriate ... previously used', 'consistent with previous analyses') is explicit, so they were kept; purely numbered citations without such language were not turned into relations. Claim type is existence (the paper establishes that these lineages and dynamics occurred); its selection analysis is closer to a null-result, since positive selection was largely absent, which the single-value facet cannot record. 2026-08-12, 2026-08-15 and 2026-08-25 schema-0.3 passes: every quote verified as an exact substring of the staged text and anchored at merge time; concept terms verified present; every edge endpoint an existing node.

11 quotations on this page contain a reference number where the paper printed a superscript. This journal style prints citations as raised numerals — parameters^12,13 — and the extraction flattened them into the line, so the sentence reads parameters 12 , 13 . The digits are citation markers and not part of what the author wrote. The quotes keep them for the same reason they keep every other extraction fault: a quote is reproduced exactly or it proves nothing.

How to read this page. The article itself is not reproduced here — this paper is not cleared for redistribution, so what follows is the tag layer alone. The evidence sentences are withheld with the article. The table at the foot lists every tag the record carries; each row names the facet it belongs to, and the whose words column says whether the tag records the paper's own wording or the tagger's sentence about the paper. Every tag links to each other paper in the corpus carrying it. The machine-readable edition of the same thing is the TEI file beside this one, where the tags live in standOff, and the article is at its publisher via the link below. When we have changed our mind. Some entries in the table begin with a word in capitals and the reason for it. EVIDENCE CORRECTED — the finding still stands, but we had quoted the wrong sentence from the paper, and the quotation has been replaced with the right one. RETRACTED — the entry itself was wrong; it stays on the page, marked, with the reason, rather than being deleted. WITHDRAWN AND REPLACED — the entry was wrong, and a corrected version of it appears in the entries below. Each mark carries its own reason, in brackets, because the reasons differ from one entry to the next. An entry we have WITHDRAWN is removed from this page and kept in the record, with its reason. A line reading Audit and a date is a later re-reading of the entry against its whole sentence: DOUBTFUL means it was kept, and the reason says what is loose about it. Quotation marks inside the tagger's sentence. Where a tag is the tagger's own sentence, a phrase in quotation marks inside it is borrowed from the paper — the tagger's wording around it is not. The paper's own sentence is the evidence quote for that row; on this page it is withheld with the article, and the article is at its publisher. Nothing inside quotation marks anywhere on this page is ours: if it is quoted, it is the paper's. Whose words a concept carries. A concept entry records a term the paper itself uses, so the term, the sense given for it, and its evidence are the paper's own words, quoted where the paper fixes them. This is the opposite of a sense entry in the tag table, which is the tagger's sentence about how the paper uses a term. Where a concept entry could not be grounded in the paper's words, the entry says so on its own row.

Other fields define these differently the same word, defined another way in another discipline
coefficient of variation 4 fields · bootstrap 2 fields · confidence interval 2 fields · positive selection 2 fields · recombination 2 fields

Tags on this paper

Every tag the record carries, each linking to every other paper in the corpus that carries it. A tag appears here whether or not its words occur in the article — the spans below are only the ones a sentence in this paper licenses. Of the 27 concept tags on this paper, 1 are grounded in a quoted sentence. All carry the tagger's gloss of what the term means in this paper, which is not something the article can license.

enterovirus 71 VP1 hand, foot, and mouth disease genogroup subgenogroup coxsackievirus A16 Picornaviridae molecular clock relaxed molecular clock Bayesian skyline plot coalescent Markov chain Monte Carlo genetic diversity purifying selection positive selection antigenic drift trunk terminal branches ladder-like temporal strain replacement cryptic recombination immunogenic influenza poliovirus toggling seroprevalence Epidemic cycles may be driven demographically rather than antigenically: susceptible children accumulate through birth until a threshold density is crossed, which then triggers large-scale transmission. The trunk-versus-terminal dN/dS gap is produced by strong purifying selection acting on all lineages combined with transient deleterious mutations that accumulate on terminal branches and are then removed. Retaining glutamic acid at the exposed, potentially immunogenic VP1 position 98 is what allows a lineage to persist long-term; lineages that substitute it die out. Because VP1 is surface-exposed and targeted by host neutralizing antibodies, it is subjected to constant immune selective pressure that can drive adaptive change in the capsid. secondary trunk lineages ladder-like tree structure core trunk enterovirus species A ratio of nonsynonymous substitutions to synonymous substitutions relative viral genetic diversity VP1 gene sequences substitution rate tMRCA nucleotide substitution model demographic model likelihood ratio test a likelihood ratio test (LRT) with one degree of freedom Bayesian Markov chain Monte Carlo the Bayesian MCMC method implemented in BEAST bootstrap multiple-comparison correction (Bonferroni) coefficient of variation posterior probability confidence interval Bayes factor maximum likelihood Maximum-likelihood analyses gamma-distributed among-site rate variation dN/dS dN / dS likelihood ratio test (LRT) Bonferroni correction Bonferroni-corrected P value cutoff credible interval maximum-likelihood (ML) Bayesian Markov chain Monte Carlo (MCMC) p-value phylogenetic-analysis

Method, as described: phylogenetic-analysis

Legend

second reading	`alternatives`	an independent re-reading of a facet, recorded whether or not it agrees
relation to other work	`claim_relations`	how this paper stands to another: agrees, contradicts, extends, qualifies
claim type	`claim_type`	the shape of the claim: existence, mechanism, method, critique, prediction, null
concept edge	`concept_edges`	an asserted relation between two concepts, with the sentence asserting it
concept	`concepts`	an idea the paper works with, quoted where the paper uses it
content tag	`content_tags`	a finding, definition, quantity, statistic or variable named in the paper
control	`controls`	an experiment run to eliminate a rival explanation
limitation	`limitations`	what the paper says its evidence cannot support
mechanism	`mechanisms`	how the reported effect is said to come about
method	`method`	how the paper produced its evidence
object of study	`object_of_study`	what the paper is about — the thing it investigates
phenomenon	`phenomenon`	the effect or regularity under study
research question	`research_question`	the question the paper sets itself
sense	`senses`	a distinct use of a term, quoted where the paper fixes it
transfer	`transfers`	a method or concept carried in from another field

The paper

The full text is not reproduced here. This article is not cleared for redistribution, so the page carries the tag layer only. Its evidence sentences are withheld; the grounding status remains with each tag, and the article itself is at https://doi.org/10.1128/jvi.01019-09. The reading view exists for the papers whose licence permits it.

Every tag on this page

alternatives 3 · claim_relations 6 · claim_type 1 · concept_edges 9 · concepts 1 · content_tags 82 · controls 1 · limitations 9 · mechanisms 10 · method 1 · object_of_study 1 · phenomenon 1 · research_question 1 · senses 8 · transfers 2

Relations on this page carry a quotation for the claim. Where a relation was separately evidenced — and so tested against the vocabulary for its type — the row says so; none of 9 relations here carry that mark. The rest are the tagger’s reading of the sentence quoted beside them.

facet	tag	field	conf.	whose words
object_of_study	The VP1 capsid gene of human enterovirus 71, read across 628 global sequences spanning four decades, as a record of the virus's origin, spread and selection. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`object_of_study`		the paper's words
research_question	When did human enterovirus 71 originate, how have its subgenogroups emerged and spread, and is the VP1 capsid gene under positive selection? Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`research_question`		the paper's words
claim_type	existence Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_type`		the paper's words
phenomenon	evolutionary dynamics of enterovirus 71 VP1 gene Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`phenomenon`		the paper's words
method	phylogenetic-analysis Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: phylogenetic-analysis	`method`		the paper's words
mechanisms	mechanisms Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Epidemic cycles may be driven demographically rather than antigenically: susceptible children accumulate through birth until a threshold density is crossed, which then triggers large-scale transmission.	`mechanisms[0]`		the tagger's words
mechanisms	mechanisms Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: The trunk-versus-terminal dN/dS gap is produced by strong purifying selection acting on all lineages combined with transient deleterious mutations that accumulate on terminal branches and are then removed.	`mechanisms[1]`		the tagger's words
mechanisms	mechanisms Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Retaining glutamic acid at the exposed, potentially immunogenic VP1 position 98 is what allows a lineage to persist long-term; lineages that substitute it die out.	`mechanisms[2]`		the tagger's words
mechanisms	mechanisms Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Because VP1 is surface-exposed and targeted by host neutralizing antibodies, it is subjected to constant immune selective pressure that can drive adaptive change in the capsid.	`mechanisms[3]`		the tagger's words
mechanisms	Subgenogroups circulate at low prevalence for years before detection, so the date of common ancestry precedes the first isolation by 1 to 5 years Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[4]`		the tagger's words
mechanisms	Rises in genetic diversity track epidemics because new subgenogroups emerging is what drives the diversity up Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[5]`		the tagger's words
mechanisms	Purifying selection dominates the whole gene while a few exposed sites show positive selection, so the genome-wide and per-site pictures point opposite ways Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[6]`		the tagger's words
mechanisms	Terminal branches carry a higher dN/dS than trunk branches because deleterious mutations appear at the tips and are removed before reaching the trunk Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[7]`		the tagger's words
mechanisms	Glutamic acid at VP1 position 98 is repeatedly lost on terminal lineages and never on the trunk, suggesting its loss ends lineages rather than propagating Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[8]`		the tagger's words
mechanisms	An alternative to antigenic escape: susceptibles accumulate by birth until a density threshold is crossed, which would produce the same periodicity without immune-driven evolution Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`mechanisms[9]`		the tagger's words
limitations	The available sequence diversity may make the estimated date of origin too recent; more archival sequencing is needed. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: the estimated date of origin: WE CANNOT AT PRESENT EXCLUDE THE POSSIBILITY THAT CURRENTLY AVAILABLE VIRUS DIVERSITY MAY UNDERESTIMATE THE DATE OF EV-71 ORIGIN	`limitations[0]`		the tagger's words
limitations	The divergence dates apply only to VP1 and may not hold for other genome regions, because recombination occurs outside VP1. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: every divergence date reported: OUR DIVERGENCE DATES SHOULD BE CONSIDERED SPECIFIC TO VP1 AND MAY NOT BE APPLICABLE TO OTHER GENOME regions, because recombination is reported outside VP1	`limitations[1]`		the tagger's words
limitations	Whether the observed diversity translates into antigenic escape in humans is not established by this work. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: the vaccine and cross-protection implications: THE DEGREE OF CROSS-PROTECTION [in humans] is not established here, only in animal models	`limitations[2]`		the tagger's words
limitations	The sampled diversity may be too shallow to reach the true origin, so the dates could be too recent Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. duplicate of: limitations[0] · what this limits: the same scope as limitations[0] - the sampled diversity may be too shallow to reach the origin	`limitations[3]`		the tagger's words
limitations	The dates apply to VP1 only, because recombination is absent here but reported elsewhere in the genome Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: the same scope as limitations[1] - VP1 only	`limitations[4]`		the tagger's words
limitations	Whether antigenic evolution drives the observed cycles is left open, and the competing explanation is not tested Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: the antigenic-evolution explanation of the epidemic cycles: WHETHER ANTIGENIC EVOLUTION IS IMPORTANT IN CAUSING THESE CYCLES IS A KEY AREA OF UNCERTAINTY	`limitations[5]`		the tagger's words
limitations	The trunk-versus-terminal selection difference rests on a p-value just above the conventional threshold Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: the trunk-versus-terminal selection difference, and read the number not the adjective: the paper calls it A SIGNIFICANTLY LOWER DN/DS RATIO and prints (P = 0.055)	`limitations[6]`		the tagger's words
limitations	Sequences were down-sampled by hand to keep the computation tractable, which is a judgement about what counts as redundant Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: every date and tree in the paper: TO REDUCE EXCESSIVE COMPUTATIONAL LOAD, CLOSELY RELATED SEQUENCES ... WERE MANUALLY REMOVED - a hand judgement about what counts as redundant, upstream of all of it	`limitations[7]`		the tagger's words
limitations	Cross-protection between subgenogroups, on which the vaccine implications depend, is unmeasured Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. what this limits: the same scope as limitations[2] - cross-protection between subgenogroups is unmeasured in humans	`limitations[8]`		the tagger's words
transfers	Influenza phylodynamics - the reading of a ladder-like phylogeny as the signature of antigenic drift - applied to EV-71, together with an explicit statement of where the analogy may fail Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`transfers[0]`		the tagger's words
transfers	Influenza vaccine strategy offered as the template for EV-71 vaccine design, conditional on EV-71 turning out to drift antigenically Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`transfers[1]`		the tagger's words
controls	all VP1 sequences screened for recombination with the Recombination Detection Program under both default and adjusted settings Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. eliminates: recombination masquerading as phylogenetic signal - a recombinant sequence puts two histories in one alignment and the tree that results is neither · outcome (stated by the tagger, no quotation): held	`controls[0]`	0.85	the tagger's words
concepts	Picornaviridae Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Picornaviridae	`concepts[6]`	0.85	the paper's words
senses	branch - core trunk: root to the most recent common ancestor of the latest isolates, the lineage that survived Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[0]`	1.0	the tagger's words
senses	branch - secondary trunk: lineages branching off the core trunk that persist an intermediate 4 to 9 years Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[1]`	1.0	the tagger's words
senses	branch - terminal: tip branches, whose mutations are transient and absent at later time points Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[2]`	1.0	the tagger's words
senses	emergence - estimated time of common ancestry, inferred from the molecular clock rather than observed Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[3]`	1.0	the tagger's words
senses	emergence - date of first isolation, which is when someone looked, not when the lineage began; the gap between the two senses IS the paper's central finding Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[4]`	1.0	the tagger's words
senses	selection - genome-wide purifying: mean dN/dS far below 1 across the whole VP1 gene in every subgenogroup Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[5]`	1.0	the tagger's words
senses	selection - site-specific positive: individual codons under positive selection, coexisting with purifying selection over the gene as a whole Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[6]`	1.0	the tagger's words
senses	genetic diversity - relative (g) reconstructed through time by the skyline plot, not a count of observed sequences Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`senses[7]`	1.0	the tagger's words
alternatives	claim_type: existence Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. a second reading reaching the same value. Recorded: existence — note: a second reading reaching the same value from a different sentence. Not applied - a person decides.	`alternatives.claim_type`		the tagger's words
alternatives	method: phylogenetic-analysis Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. a second reading reaching the same value. Recorded: phylogenetic-analysis — note: a second reading reaching the same value from a different sentence. Not applied - a person decides.	`alternatives.method`		the tagger's words
alternatives	phenomenon: evolutionary dynamics of enterovirus 71 VP1 gene Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. a second reading reaching the same value. Recorded: evolutionary dynamics of enterovirus 71 VP1 gene — note: a second reading reaching the same value from a different sentence. Not applied - a person decides.	`alternatives.phenomenon`		the tagger's words
claim_relations	contradicts → earlier EV-71 substitution-rate estimates obtained by linear regression (reference 11) Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[0]`		the tagger's words
claim_relations	replicates → previous analyses of recombination in human enterovirus species (reference 73) Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[1]`		the tagger's words
claim_relations	extends → earlier EV-71 substitution rate estimates made by linear regression Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[2]`		the tagger's words
claim_relations	supports → the comparative finding that trunk branches carry lower dN/dS than terminal branches across RNA viruses Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[3]`		the tagger's words
claim_relations	supports → the influenza A finding that rises in genetic diversity accompany epidemics Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[4]`		the tagger's words
claim_relations	supports → Bible and colleagues on cell culture having negligible effect on VP1 sequence Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`claim_relations[5]`		the tagger's words
concept_edges	enterovirus 71 —part-of→ Picornaviridae Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 also in: enterovirus 71 · Picornaviridae	`concept_edges[0]`		the tagger's words
concept_edges	subgenogroup —part-of→ genogroup Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 also in: subgenogroup · genogroup	`concept_edges[1]`		the tagger's words
concept_edges	VP1 —part-of→ enterovirus 71 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span writes 'EV-71'; endpoint abbreviated. also in: VP1 · enterovirus 71	`concept_edges[2]`		the tagger's words
concept_edges	purifying selection —contrasted-with→ positive selection Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span writes 'negative selection' against others' 'positive selection'; endpoint variant. also in: purifying selection · positive selection	`concept_edges[4]`		the tagger's words
concept_edges	trunk —contrasted-with→ terminal branches Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 also in: trunk · terminal branches	`concept_edges[6]`		the tagger's words
concept_edges	genetic diversity —operationalised-as→ Bayesian skyline plot Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 also in: genetic diversity · Bayesian skyline plot	`concept_edges[7]`		the tagger's words
concept_edges	subgenogroup —causes→ genetic diversity Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 0.8 also in: subgenogroup · genetic diversity	`concept_edges[8]`		the tagger's words
concept_edges	RETRACTED (NEITHER ENDPOINT IS NAMED IN ITS OWN SPAN) · antigenic drift —causes→ ladder-like Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. RETRACTED: NEITHER ENDPOINT IS NAMED IN ITS OWN SPAN. The edge is 'antigenic drift --causes--> ladder-like'; the span reads: Quotation withheld, with limited genetic diversity at any one time. It says this process, not antigenic drift, and the strongly temporal shape, not ladder-like. A span that names neither endpoint cannot assert a relation between them - the criterion's plainest case - and it is compounded by has been linked to, which is both relational and attributed to other work. WHAT THE SPAN DOES SAY: nothing about these two terms, so nothing is kept. would reject this edge today; it predates the rule. — strength of the relation: 0.5 — the record marks this weak Audit 2026-09-28: DOUBTFUL - read against its span and kept, but antigenic drift has been linked to temporal phylogeny shapes; causes is loose. also in: antigenic drift · ladder-like	`concept_edges[10]`		the tagger's words
concept_edges	enterovirus 71 —contrasted-with→ influenza Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. strength of the relation: 1 Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but endpoint by anaphora: 'Both phylogenies' = subgenogroup C1 isolates and influenza virus A (previous sentence). also in: enterovirus 71 · influenza	`concept_edges[12]`		the tagger's words
content_tags	likelihood ratio test Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: likelihood ratio test	`content_tags.statistics[0]`		the tagger's words
content_tags	Bayesian Markov chain Monte Carlo Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Bayesian Markov chain Monte Carlo	`content_tags.statistics[1]`		the tagger's words
content_tags	bootstrap Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: bootstrap	`content_tags.statistics[2]`		the tagger's words
content_tags	multiple-comparison correction (Bonferroni) Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: multiple-comparison correction (Bonferroni)	`content_tags.statistics[3]`		the tagger's words
content_tags	coefficient of variation Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: coefficient of variation	`content_tags.statistics[4]`		the tagger's words
content_tags	posterior probability Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: posterior probability	`content_tags.statistics[5]`		the tagger's words
content_tags	confidence interval Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: confidence interval	`content_tags.statistics[6]`		the tagger's words
content_tags	Bayes factor Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Bayes factor	`content_tags.statistics[7]`		the tagger's words
content_tags	maximum likelihood Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: maximum likelihood	`content_tags.statistics[8]`		the tagger's words
content_tags	gamma-distributed among-site rate variation Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: gamma-distributed among-site rate variation	`content_tags.statistics[9]`		the tagger's words
content_tags	dN/dS Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: dN/dS	`content_tags.statistics[10]`		the tagger's words
content_tags	likelihood ratio test Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: likelihood ratio test	`content_tags.statistics[11]`		the tagger's words
content_tags	Bayes factor Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Bayes factor	`content_tags.statistics[12]`		the tagger's words
content_tags	Bonferroni correction Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Bonferroni correction	`content_tags.statistics[13]`		the tagger's words
content_tags	credible interval Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: credible interval	`content_tags.statistics[14]`		the tagger's words
content_tags	confidence interval Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: confidence interval	`content_tags.statistics[15]`		the tagger's words
content_tags	coefficient of variation Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: coefficient of variation	`content_tags.statistics[16]`		the tagger's words
content_tags	posterior probability Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: posterior probability	`content_tags.statistics[17]`		the tagger's words
content_tags	maximum likelihood Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: maximum likelihood	`content_tags.statistics[18]`		the tagger's words
content_tags	bootstrap Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: bootstrap	`content_tags.statistics[19]`		the tagger's words
content_tags	Markov chain Monte Carlo Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Markov chain Monte Carlo	`content_tags.statistics[20]`		the tagger's words
content_tags	p-value Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: p-value	`content_tags.statistics[21]`		the tagger's words
content_tags	The common ancestor of human enterovirus 71 is dated to about 1941, after which the virus split into genogroups B, C and the now-extinct genogroup A. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[0]`		the tagger's words
content_tags	Each subgenogroup of genogroups B and C circulated undetected in humans for up to five years before it caused a large hand, foot and mouth disease outbreak. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[1]`		the tagger's words
content_tags	The VP1 gene evolves under strong purifying selection, with mean dN/dS between 0.029 and 0.075 in every subgenogroup except B3. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[2]`		the tagger's words
content_tags	In subgenogroup C1 the trunk lineages have a lower dN/dS (0.030) than the terminal lineages (0.064), the opposite of the pattern expected under antigenic-drift-style positive selection along the trunk. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[3]`		the tagger's words
content_tags	No homologous recombination was detectable in the capsid-encoding VP1 region, so the phylogenetic and dating analyses are not confounded by recombination. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[4]`		the tagger's words
content_tags	Rises in viral genetic diversity coincide with epidemic onsets and are driven partly by the appearance of new subgenogroups. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[5]`		the tagger's words
content_tags	VP1 codon 98 changed repeatedly and unidirectionally (glutamic acid to lysine or glycine) on terminal branches but never on trunk branches, so lineages that acquired the change did not persist. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[6]`		the tagger's words
content_tags	A demographic model of exponential population growth fits the VP1 data far better than a constant-population-size model. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[7]`		the tagger's words
content_tags	Several trunk residues toggled back and forth over time: position 145 went glutamic acid to glutamine and back, 262 isoleucine to valine and back, and 289 alanine to threonine and back. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[8]`		the tagger's words
content_tags	Subgenogroups B1 to B5, C1, C2 and C4 are globally distributed, whereas C3 is confined to Korea and C5 to Vietnam. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[9]`		the tagger's words
content_tags	The VP1 gene evolves at about 4.2 to 4.6 x 10^-3 substitutions per site per year, higher than earlier linear-regression estimates. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[10]`		the tagger's words
content_tags	Choice of coalescent demographic model made no significant difference to the estimated divergence dates. Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[11]`		the tagger's words
content_tags	the common ancestor of EV-71 dates to about 1941 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[12]`		the tagger's words
content_tags	each subgenogroup circulated undetected for 1 to 5 years before its first outbreak Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[13]`		the tagger's words
content_tags	the same subgenogroup in different countries reflects separate lineages, not one strain travelling Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[14]`		the tagger's words
content_tags	VP1 evolves under strong purifying selection despite substitution rates comparable to influenza and HIV-1 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[15]`		the tagger's words
content_tags	trunk lineages carry a lower dN/dS than terminal lineages in subgenogroup C1 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[16]`		the tagger's words
content_tags	position 98 changes repeatedly on terminal lineages and never on the trunk, and the changes are directional Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[17]`		the tagger's words
content_tags	amino acids toggle - changing and reverting - on the core trunk over 3 to 5 year spans Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[18]`		the tagger's words
content_tags	only 14 nonsynonymous substitutions occur on the trunk, at 10 sites Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[19]`		the tagger's words
content_tags	no recombination was detectable in VP1 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[20]`		the tagger's words
content_tags	reconstructed diversity dynamics match four decades of independent surveillance data Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[21]`		the tagger's words
content_tags	exponential growth fits the data better than constant population size Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[22]`		the tagger's words
content_tags	C3 and C5 are geographically restricted while the other subgenogroups are cosmopolitan Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[23]`		the tagger's words
content_tags	outbreaks recur on a roughly 2 to 3 year cycle Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.findings[24]`		the tagger's words
content_tags	terminal branches Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: terminal branches	`content_tags.definitions[0]`		the tagger's words
content_tags	secondary trunk lineages Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: secondary trunk lineages	`content_tags.definitions[1]`		the tagger's words
content_tags	ladder-like tree structure Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: ladder-like tree structure	`content_tags.definitions[2]`		the tagger's words
content_tags	antigenic drift Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: antigenic drift	`content_tags.definitions[3]`		the tagger's words
content_tags	core trunk Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: core trunk	`content_tags.definitions[5]`		the tagger's words
content_tags	Bayesian skyline plot Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: Bayesian skyline plot	`content_tags.definitions[6]`		the tagger's words
content_tags	relaxed molecular clock Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: relaxed molecular clock	`content_tags.definitions[7]`		the tagger's words
content_tags	toggling Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: toggling	`content_tags.definitions[8]`		the tagger's words
content_tags	enterovirus species A Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: enterovirus species A	`content_tags.definitions[9]`		the tagger's words
content_tags	ratio of nonsynonymous substitutions to synonymous substitutions Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: ratio of nonsynonymous substitutions to synonymous substitutions	`content_tags.variables[0]`		the tagger's words
content_tags	relative viral genetic diversity Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: relative viral genetic diversity	`content_tags.variables[3]`		the tagger's words
content_tags	VP1 gene sequences Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: VP1 gene sequences	`content_tags.variables[4]`		the tagger's words
content_tags	substitution rate Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: substitution rate	`content_tags.variables[5]`		the tagger's words
content_tags	tMRCA Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: tMRCA	`content_tags.variables[6]`		the tagger's words
content_tags	nucleotide substitution model Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: nucleotide substitution model	`content_tags.variables[9]`		the tagger's words
content_tags	demographic model Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above. also in: demographic model	`content_tags.variables[10]`		the tagger's words
content_tags	628 — Number of complete VP1 gene sequences with known collection dates analysed, effectively all reported EV-71 VP1 genes as of mid-2008 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[0]`		the tagger's words
content_tags	1941.0 (95% CR, 1928.8 to 1952.2) — Estimated date of origin of EV-71 as a descendant of coxsackievirus A16 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[1]`		the tagger's words
content_tags	229 and 251 — Sizes of the down-sampled genogroup B and C alignments used for the Bayesian MCMC analyses Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[2]`		the tagger's words
content_tags	0.030 ± 0.009 ... 0.064 ± 0.008 ( P = 0.055) — dN/dS on trunk versus terminal lineages of subgenogroup C1, and the significance of the difference Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[3]`		the tagger's words
content_tags	14 ... 10 — Number of nonsynonymous substitutions observed on subgenogroup C1 trunk branches and the number of distinct sites at which they occurred Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[4]`		the tagger's words
content_tags	every 2 to 3 years — Observed periodicity of EV-71 outbreaks Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[5]`		the tagger's words
content_tags	145 ( P < 0.05), 98 ( P < 0.05), 237, and 241 ( P < 0.05) — VP1 codon positions detected as being under positive selection in well-sampled subgenogroups Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[6]`		the tagger's words
content_tags	about 3 to 5 years — Length of time a toggled residue persisted on the core trunk branches before reverting Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[7]`		the tagger's words
content_tags	1 to 5 years — Lag between the date of common ancestry of a genogroup C subgenogroup and its first identification Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[8]`		the tagger's words
content_tags	628 — VP1 sequences analysed, essentially every one then reported Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[9]`		the tagger's words
content_tags	1941.0 (95% CR, 1928.8 to 1952.2) — the estimated origin of EV-71, decades before its first isolation in 1969 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[10]`		the tagger's words
content_tags	4.5 × 10 −3 to 4.6 × 10 −3 — substitutions per site per year in genogroup B Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[11]`		the tagger's words
content_tags	0.029 to 0.075 — the range of mean dN/dS across subgenogroups, all far below 1 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[12]`		the tagger's words
content_tags	2 to 5 years — how long genogroup B subgenogroups circulated before causing large outbreaks Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[13]`		the tagger's words
content_tags	20 million states — the MCMC chain length, sampled every 10,000 Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[14]`		the tagger's words
content_tags	229 and 251 sequences — the down-sampled genogroup B and C data sets actually used for the clock analysis Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[15]`		the tagger's words
content_tags	approximately 7,400 bases — the EV-71 genome length Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[16]`		the tagger's words
content_tags	every 2 to 3 years — the apparent outbreak periodicity the discussion tries to explain Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[17]`		the tagger's words
content_tags	1969 — first isolation of EV-71, nearly three decades after the inferred origin Quotation withheld — this record is not cleared for redistribution. The sentence is in the paper at the link above.	`content_tags.quantities[18]`		the tagger's words

Interpretive choices

Tags that could not be placed in the text:

none — every tag was located in the text

What was deliberately not tagged, and why, is recorded per paper by the tagger. Where a paper has no such record, this page says so rather than implying that nothing was declined.