Evolutionary Genetics of Human Enterovirus 71: Origin, Population Dynamics, Natural Selection, and Seasonal Periodicity of the VP1 Gene — TEI-tagged view

Kok Keng Tee, Tommy Tsan‐Yuk Lam, Yoke Fun Chan, Jon M. Bible, Adeeba Kamarulzaman, C. Y. William Tong, Yutaka Takebe, Oliver G. Pybus · 2010 · evolutionary-virology · doi:10.1128/jvi.01019-09 · full text at the source · TEI xml · tagged edition · index · concepts · authors
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 — parameters12,13 — 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.
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, whether or not the words occur in the text below — a number is how many papers in the corpus carry that tag; a tag with no number is unique to this paper
enterovirus 71 VP1 hand, foot, and mouth disease genogroup subgenogroup coxsackievirus A16 Picornaviridae molecular clock2 relaxed molecular clock Bayesian skyline plot coalescent Markov chain Monte Carlo4 genetic diversity purifying selection2 positive selection3 antigenic drift trunk terminal branches ladder-like temporal strain replacement cryptic recombination3 immunogenic influenza poliovirus toggling seroprevalence phylogenetic-analysis6
Method, as described: phylogenetic-analysis

Our tag layer for this paper

Cross-disciplinary analysis
content-tags & facets: phenomenon · claim-type · cross-domain-transfer · mechanism · claim-relation · replication-status · limitation — grounded in the full text
phenomenonevolutionary dynamics of enterovirus 71 VP1 gene— “In this study, we investigated the evolutionary dynamics and genetic history of EV-71.”
claim-typeexistence— “Genealogical analysis revealed that diverse lineages of genogroup B and C (subgenogroups B1 to B5 and C1 to C5) have each circulated cryptically in the human population for up to 5 years before causing large HFMD outbreaks, indicating the quiescent persistence of EV-71 in human populations.”
method — evidence— “Global VP1 capsid sequences ( n = 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods.”
object of study — evidence— “Global VP1 capsid sequences ( n = 628) sampled over 4 decades were collected and subjected to comprehensive evolutionary analysis using a suite of phylogenetic and population genetic methods.”
research question — evidence— “In this study, we investigated the evolutionary dynamics and genetic history of EV-71.”
transferfrom : 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— “Although influenza virus-like antigenic evolution is one possible explanation of the observed EV-71 phylogeny shape, it is not without problems. Other enteroviruses, notably poliovirus, have remained antigenically stable for many years.”transfers[0]
transferfrom : Influenza vaccine strategy offered as the template for EV-71 vaccine design, conditional on EV-71 turning out to drift antigenically— “Little is known about EV-71 genetic diversity; however, if it does exhibit influenza virus-like antigenic drift, then the strategies adopted in developing an influenza virus vaccine may be relevant for EV-71.”transfers[1]
mechanismEpidemic 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.— “Specifically, gradual accumulation of susceptible hosts through birth ( 40 ) and low EV-71 seroprevalence or seroconversion rates at the population level ( 17 , 42 ) may trigger large-scale viral transmission once a threshold density of susceptible hosts is reached.”mechanisms[0]
mechanismThe 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.— “This is best explained by a combination of strong purifying selection on all lineages, as proposed above, combined with a greater occurrence of transient deleterious mutations on terminal branches than on trunk branches.”mechanisms[1]
mechanismRetaining 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.— “The finding suggests that the maintenance of glutamic acid at position 98, which is completely exposed on the VP1 capsid surface and thus potentially immunogenic ( 66 ), might be important for the long-term persistence of subgenogroup C1.”mechanisms[2]
mechanismBecause 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.— “The VP1 protein is highly exposed and usually targeted by host neutralizing antibodies, predisposing the VP1 gene to constant immune selective pressure.”mechanisms[3]
mechanismSubgenogroups circulate at low prevalence for years before detection, so the date of common ancestry precedes the first isolation by 1 to 5 years— “The cryptic circulation of each EV-71 subgenogroup for years prior to its detection suggests that (i) the virus was circulating at low prevalence, such that the number of HFMD cases was small and occasional or no deaths were reported, and/or (ii) infection symptoms were not severe during the course of infection ( 17 ), thus attracting little…mechanisms[4]
mechanismRises in genetic diversity track epidemics because new subgenogroups emerging is what drives the diversity up— “Further, the increase in genetic diversity—most evident in the late 1990s—is likely a consequence, at least in part, of the emergence of heterogeneous EV-71 subgenogroups.”mechanisms[5]
mechanismPurifying selection dominates the whole gene while a few exposed sites show positive selection, so the genome-wide and per-site pictures point opposite ways— “Maximum-likelihood analyses showed that the evolution of EV-71 is driven by strong purifying selection, with estimates of mean dN / dS values ranging from 0.029 to 0.075 for all subgenogroups (except B3, for which the mean dN / dS is significantly higher) (Table 2 ).”mechanisms[6]
mechanismTerminal branches carry a higher dN/dS than trunk branches because deleterious mutations appear at the tips and are removed before reaching the trunk— “This is best explained by a combination of strong purifying selection on all lineages, as proposed above, combined with a greater occurrence of transient deleterious mutations on terminal branches than on trunk branches.”mechanisms[7]
mechanismGlutamic acid at VP1 position 98 is repeatedly lost on terminal lineages and never on the trunk, suggesting its loss ends lineages rather than propagating— “The finding suggests that the maintenance of glutamic acid at position 98, which is completely exposed on the VP1 capsid surface and thus potentially immunogenic ( 66 ), might be important for the long-term persistence of subgenogroup C1.”mechanisms[8]
mechanismAn alternative to antigenic escape: susceptibles accumulate by birth until a density threshold is crossed, which would produce the same periodicity without immune-driven evolution— “Specifically, gradual accumulation of susceptible hosts through birth ( 40 ) and low EV-71 seroprevalence or seroconversion rates at the population level ( 17 , 42 ) may trigger large-scale viral transmission once a threshold density of susceptible hosts is reached.”mechanisms[9]
contradicts earlier EV-71 substitution-rate estimates obtained by linear regression (reference 11)— “The estimated substitution rates for genogroups B and C are similar and higher than those estimated using the less statistically appropriate linear regression method previously used ( 11 ).”claim_relations[0]
replicates previous analyses of recombination in human enterovirus species (reference 73)— “Additionally, rigorous recombination analysis showed a lack of recombination in the capsid-encoding VP1 region, consistent with previous analyses on human enterovirus species ( 73 ).”claim_relations[1]
extends earlier EV-71 substitution rate estimates made by linear regression— “The estimated substitution rates for genogroups B and C are similar and higher than those estimated using the less statistically appropriate linear regression method previously used ( 11 ).”claim_relations[2]
supports the comparative finding that trunk branches carry lower dN/dS than terminal branches across RNA viruses— “This is in agreement with the conclusions of a comparative study that found the same pattern in most RNA viruses ( 61 ).”claim_relations[3]
supports the influenza A finding that rises in genetic diversity accompany epidemicsclaim_relations[4]
supports Bible and colleagues on cell culture having negligible effect on VP1 sequenceclaim_relations[5]
sensebranch - core trunk: root to the most recent common ancestor of the latest isolates, the lineage that survivedsenses[0]
sensebranch - secondary trunk: lineages branching off the core trunk that persist an intermediate 4 to 9 years
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senses[1]
sensebranch - terminal: tip branches, whose mutations are transient and absent at later time points
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senses[2]
senseemergence - estimated time of common ancestry, inferred from the molecular clock rather than observed
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senses[3]
senseemergence - 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
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senses[4]
senseselection - genome-wide purifying: mean dN/dS far below 1 across the whole VP1 gene in every subgenogroup
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senses[5]
senseselection - site-specific positive: individual codons under positive selection, coexisting with purifying selection over the gene as a whole
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senses[6]
sensegenetic diversity - relative (g) reconstructed through time by the skyline plot, not a count of observed sequences
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senses[7]
controlall VP1 sequences screened for recombination with the Recombination Detection Program under both default and adjusted settings — held — rules out recombination masquerading as phylogenetic signal - a recombinant sequence puts two histories in one alignment and the tree that results is neither
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controls[0]
edgeenterovirus 71 —part-of→ Picornaviridae
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concept_edges[0]
edgesubgenogroup —part-of→ genogroup
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concept_edges[1]
auditVP1 —part-of→ enterovirus 71 — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span writes 'EV-71'; endpoint abbreviated.
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concept_edges[2]
auditpurifying selection —contrasted-with→ positive selection — Audit 2026-09-28: DOUBTFUL - read against its full span and kept, but the span writes 'negative selection' against others' 'positive selection'; endpoint variant.
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concept_edges[4]
edgetrunk —contrasted-with→ terminal branches
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concept_edges[6]
edgegenetic diversity —operationalised-as→ Bayesian skyline plot
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concept_edges[7]
weightsubgenogroup —causes→ genetic diversity — 0.8
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concept_edges[8]
auditRETRACTED (NEITHER ENDPOINT IS NAMED IN ITS OWN SPAN) · antigenic drift —causes→ ladder-like — Audit 2026-09-28: DOUBTFUL - read against its span and kept, but antigenic drift has been linked to temporal phylogeny shapes; causes is loose.
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concept_edges[10]
retractedRETRACTED (NEITHER ENDPOINT IS NAMED IN ITS OWN SPAN) · antigenic drift —causes→ ladder-like — NEITHER ENDPOINT IS NAMED IN ITS OWN SPAN. The edge is 'antigenic drift --causes--> ladder-like'; the span reads: This process has been LINKED TO the strongly temporal shape of influenza virus phylogenies, 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.
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Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concept_edges[10]
weightRETRACTED (NEITHER ENDPOINT IS NAMED IN ITS OWN SPAN) · antigenic drift —causes→ ladder-like — 0.5
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concept_edges[10]
auditenterovirus 71 —contrasted-with→ influenza — 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).
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concept_edges[12]
outcome (stated by the tagger, no quotation)control — heldcontrols[0]
for which uselimitation — 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
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limitations[0]
for which uselimitation — 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
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limitations[1]
for which uselimitation — the vaccine and cross-protection implications: THE DEGREE OF CROSS-PROTECTION [in humans] is not established here, only in animal models
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limitations[2]
duplicate oflimitation — limitations[0]
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limitations[3]
for which uselimitation — the same scope as limitations[0] - the sampled diversity may be too shallow to reach the origin
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limitations[3]
for which uselimitation — the same scope as limitations[1] - VP1 only
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limitations[4]
for which uselimitation — the antigenic-evolution explanation of the epidemic cycles: WHETHER ANTIGENIC EVOLUTION IS IMPORTANT IN CAUSING THESE CYCLES IS A KEY AREA OF UNCERTAINTY
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limitations[5]
for which uselimitation — 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)
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limitations[6]
for which uselimitation — 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
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limitations[7]
for which uselimitation — the same scope as limitations[2] - cross-protection between subgenogroups is unmeasured in humans
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limitations[8]
replicationuntested
limitationThe available sequence diversity may make the estimated date of origin too recent; more archival sequencing is needed.
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limitations[0]
limitationThe divergence dates apply only to VP1 and may not hold for other genome regions, because recombination occurs outside VP1.
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limitations[1]
limitationWhether the observed diversity translates into antigenic escape in humans is not established by this work.
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limitations[2]
limitationThe sampled diversity may be too shallow to reach the true origin, so the dates could be too recent
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limitations[3]
limitationThe dates apply to VP1 only, because recombination is absent here but reported elsewhere in the genome
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limitations[4]
limitationWhether antigenic evolution drives the observed cycles is left open, and the competing explanation is not tested
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limitations[5]
limitationThe trunk-versus-terminal selection difference rests on a p-value just above the conventional threshold
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limitations[6]
limitationSequences were down-sampled by hand to keep the computation tractable, which is a judgement about what counts as redundant
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limitations[7]
limitationCross-protection between subgenogroups, on which the vaccine implications depend, is unmeasured
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limitations[8]
Content tags
content-observations: finding · quantity · variable · definition · key-term — grounded in the full text
findingThe 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.
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content_tags.findings[0]
findingEach 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.
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content_tags.findings[1]
findingThe VP1 gene evolves under strong purifying selection, with mean dN/dS between 0.029 and 0.075 in every subgenogroup except B3.
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content_tags.findings[2]
findingIn 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.
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content_tags.findings[3]
findingNo homologous recombination was detectable in the capsid-encoding VP1 region, so the phylogenetic and dating analyses are not confounded by recombination.
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content_tags.findings[4]
findingRises in viral genetic diversity coincide with epidemic onsets and are driven partly by the appearance of new subgenogroups.
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content_tags.findings[5]
findingVP1 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.
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content_tags.findings[6]
findingA demographic model of exponential population growth fits the VP1 data far better than a constant-population-size model.
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content_tags.findings[7]
findingSeveral 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.
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content_tags.findings[8]
findingSubgenogroups B1 to B5, C1, C2 and C4 are globally distributed, whereas C3 is confined to Korea and C5 to Vietnam.
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content_tags.findings[9]
findingThe VP1 gene evolves at about 4.2 to 4.6 x 10^-3 substitutions per site per year, higher than earlier linear-regression estimates.
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content_tags.findings[10]
findingChoice of coalescent demographic model made no significant difference to the estimated divergence dates.
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content_tags.findings[11]
findingthe common ancestor of EV-71 dates to about 1941
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content_tags.findings[12]
findingeach subgenogroup circulated undetected for 1 to 5 years before its first outbreak
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content_tags.findings[13]
findingthe same subgenogroup in different countries reflects separate lineages, not one strain travelling
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content_tags.findings[14]
findingVP1 evolves under strong purifying selection despite substitution rates comparable to influenza and HIV-1
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content_tags.findings[15]
findingtrunk lineages carry a lower dN/dS than terminal lineages in subgenogroup C1
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content_tags.findings[16]
findingposition 98 changes repeatedly on terminal lineages and never on the trunk, and the changes are directional
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content_tags.findings[17]
findingamino acids toggle - changing and reverting - on the core trunk over 3 to 5 year spans
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content_tags.findings[18]
findingonly 14 nonsynonymous substitutions occur on the trunk, at 10 sites
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content_tags.findings[19]
findingno recombination was detectable in VP1
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content_tags.findings[20]
findingreconstructed diversity dynamics match four decades of independent surveillance data
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content_tags.findings[21]
findingexponential growth fits the data better than constant population size
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content_tags.findings[22]
findingC3 and C5 are geographically restricted while the other subgenogroups are cosmopolitan
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content_tags.findings[23]
findingoutbreaks recur on a roughly 2 to 3 year cycle
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content_tags.findings[24]
quantity628 — 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 paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[0]
quantity1941.0 (95% CR, 1928.8 to 1952.2) — Estimated date of origin of EV-71 as a descendant of coxsackievirus A16
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[1]
quantity229 and 251 — Sizes of the down-sampled genogroup B and C alignments used for the Bayesian MCMC analyses
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[2]
quantity0.030 ± 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 paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[3]
quantity14 ... 10 — Number of nonsynonymous substitutions observed on subgenogroup C1 trunk branches and the number of distinct sites at which they occurred
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[4]
quantityevery 2 to 3 years — Observed periodicity of EV-71 outbreaks
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[5]
quantity145 ( 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 paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[6]
quantityabout 3 to 5 years — Length of time a toggled residue persisted on the core trunk branches before reverting
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[7]
quantity1 to 5 years — Lag between the date of common ancestry of a genogroup C subgenogroup and its first identification
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[8]
quantity628 — VP1 sequences analysed, essentially every one then reported
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[9]
quantity1941.0 (95% CR, 1928.8 to 1952.2) — the estimated origin of EV-71, decades before its first isolation in 1969
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[10]
quantity4.5 × 10 −3 to 4.6 × 10 −3 — substitutions per site per year in genogroup B
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[11]
quantity0.029 to 0.075 — the range of mean dN/dS across subgenogroups, all far below 1
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[12]
quantity2 to 5 years — how long genogroup B subgenogroups circulated before causing large outbreaks
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[13]
quantity20 million states — the MCMC chain length, sampled every 10,000
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[14]
quantity229 and 251 sequences — the down-sampled genogroup B and C data sets actually used for the clock analysis
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[15]
quantityapproximately 7,400 bases — the EV-71 genome length
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[16]
quantityevery 2 to 3 years — the apparent outbreak periodicity the discussion tries to explain
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[17]
quantity1969 — first isolation of EV-71, nearly three decades after the inferred origin
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.quantities[18]
variableratio of nonsynonymous substitutions to synonymous substitutions (dependent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[0]
variablerelative viral genetic diversity (dependent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[3]
variableVP1 gene sequences (independent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[4]
variablesubstitution rate (dependent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[5]
variabletMRCA (dependent)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[6]
variablenucleotide substitution model (control)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[9]
variabledemographic model (control)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.variables[10]
definitionterminal branches
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[0]
definitionsecondary trunk lineages
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[1]
definitionladder-like tree structure
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[2]
definitionantigenic drift
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[3]
definitioncore trunk
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[5]
definitionBayesian skyline plot
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[6]
definitionrelaxed molecular clock
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[7]
definitiontoggling
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[8]
definitionenterovirus species A
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.definitions[9]
key-termsenterovirus 71, VP1, hand, foot, and mouth disease, genogroup, subgenogroup, coxsackievirus A16, molecular clock, Bayesian skyline plot, coalescent, purifying selection, positive selection, antigenic drift, trunk, terminal branches, ladder-like, temporal strain replacement, recombination, toggling, seroprevalence, immunogenic
Concepts
terms this paper carries, each with the sentence it was cut from — the layer that joins one paper to another. Terms with no quote yet are on CONCEPTS.html.
conceptPicornaviridae — not defined in this paper's own words; the family containing the genus Enterovirus
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
concepts[6]
Statistics — cross-field join keys
field-invariant statistical terms, used in their statistical sense (gated on a number / symbol / test). A p-value or a standard deviation means the SAME thing in physics, biology, psychology and sociology — so these are the strongest cross-field join keys. Grounded verbatim.
likelihood ratio test LRT as written: a likelihood ratio test (LRT) with one degree of freedom
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[0]
Bayesian Markov chain Monte Carlo MCMC as written: the Bayesian MCMC method implemented in BEAST
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[1]
bootstrap as written: significant bootstrap support values (≥80%; 1,000 bootstrap replicates)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[2]
multiple-comparison correction (Bonferroni) P as written: a Bonferroni-corrected P value cutoff of 0.05
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[3]
coefficient of variation as written: an estimated coefficient of variation of 0.44
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[4]
posterior probability as written: Posterior probabilities were calculated with a burn-in of 2 million states
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[5]
confidence interval CI as written: 95% confidence interval [CI]
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content_tags.statistics[6]
Bayes factor as written: log 10 Bayes factor, 7.6
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content_tags.statistics[7]
maximum likelihood as written: Maximum-likelihood analyses
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[8]
gamma-distributed among-site rate variation γ 4 as written: a gamma-distributed among-site rate variation with four rate categories (γ 4 )
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[9]
dN/dS
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[10]
likelihood ratio test as written: likelihood ratio test (LRT)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[11]
Bayes factor as written: log 10 Bayes factor
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[12]
Bonferroni correction as written: Bonferroni-corrected P value cutoff
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[13]
credible interval as written: 95% credible region [CR]
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[14]
confidence interval as written: 95% confidence interval [CI]
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[15]
coefficient of variation
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[16]
posterior probability
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[17]
maximum likelihood as written: maximum-likelihood (ML)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[18]
bootstrap as written: 1,000 bootstrap replicates
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[19]
Markov chain Monte Carlo as written: Bayesian Markov chain Monte Carlo (MCMC)
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[20]
p-value as written: P = 0.055
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
content_tags.statistics[21]
Second readings
a facet read a second time, independently, from its own sentence — and whether the two readings agree
claim typeexistence — a second reading reaching the same value; recorded: existence
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
alternatives.claim_type
methodphylogenetic-analysis — a second reading reaching the same value; recorded: phylogenetic-analysis
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
alternatives.method
phenomenonevolutionary dynamics of enterovirus 71 VP1 gene — a second reading reaching the same value; recorded: evolutionary dynamics of enterovirus 71 VP1 gene
Quotation withheld — this paper is not ours to reproduce, and the page has already quoted as much of it as the rights layer allows. The tag, its field and its confidence stand; the sentence is at the publisher.
alternatives.phenomenon

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.

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