Reading List

The origin and evolution of Ebola and Marburg viruses.

Suzuki, Y; Gojobori, T. (1997).
Molecular Biology and Evolution. 14 (8)
doi:10.1093/oxfordjournals.molbev.a025820.
 These viruses have also been classified into the genus Filovirus, which is the sole
member of the family Filoviridue
 genomes encode same set of seven genes in the same order, namely nucleoprotein
(NP), viral structural protein 35 (VP35), VP40, glycoprotein (GP), VP30, VP24, and
RNA-dependent RNA polymerase (L), from the 3’ to 5’ end.
 On glycoprotein gene, rate of non-synonymous mutations 3.6E-5 per site per year
 could not estimate the rate of synonymous substitutions because the number of
synonymous substitutions among different virus strains of Ebola virus or between
Ebola and Mar-burg viruses was so large that we could not estimate it accurately.
 dN 100x slower than retroviruses and human influenza A. Same order of magnitude
as Hepatitus B virus. Why is it relatively slow?
 Rates applied to sequence divergence, estimated divergence between ebola and
Marburg virus to be several thousand years ago
 Estimated on the assumption that these viruses had evolved at almost the same
substitution rate.
 All nucleotide changes between them assumed to have occurred through single-
nucleotide substitutions (sequences had high similarity 94-97%)
 Most substitutions were synonymous transitions( (suggests purifying selection)
Complete genome sequence of an Ebola virus (Sudan species) responsible for a 2000
outbreak of human disease in Uganda
Sanchez and Rollin, 2005
Volume 113
https://www.sciencedirect.com/science/article/pii/S0168170205000961
 Genomic RNA of Gulu strain (Uganda 2000) sequenced.
 first comprehensive genetic analysis for Sudan species of Ebola virus
 Genomic organisation of Sudan nearly identical to Zaire
 gene overlap (between GP and VP30genes) and a longer trailer sequence than Reston
 stem loop structures were predicted to form at the 5 ′end of Ebola Sudan mRNA molecules,
 Genomic RNA termini showed a high degree of sequence complementarity.
 Amino acid sequence comparisons (of encoded gene products) show Sudan and Zaire are
more similar to the Reston species than to one another
 Comparisons also indicated VP24 is the most conserved Ebola virus protein (followed
closely by the VP40and L proteins), while the GP is the least conserved gene product.
 most divergent regions are C-terminus of GP1 (mucin-like region) and C-terminal third of
the nucleoprotein sequence
BEAST: Bayesian evolutionary analysis by sampling trees
Drummond and Rambaut
BMC Evolutionary Biology, Volume 214, 2007
https://bmcevolbiol.biomedcentral.com/articles/10.1186/1471-2148-7-214
-Covering in ToL
Filoviruses are ancient and integrated into mammalian genomes
Taylor, D.; Leach, R.; Bruenn, J. (2010). BMC Evolutionary Biology. 10:193.
doi:10.1186/1471-2148-10-193. PMC 2906475. PMID 20569424.
 Sequenced across host-virus gene boundaries, and did phylogenetic analysis
  Tested for association between candidate reservoir status and integration of
filoviral elements to re-assess previous estimate of filoviruses as 10,000 years old
 Phylogenetic and sequence gene boundaries indicated integration of filoviruses in
mammalian genomes
 integrated filovirus-like elements detected in the genomes of bats, rodents,
shrews, tenrecs and marsupials. Some filovirus-like elements were transcribed and
detected mammalian elements were homologous to a fragment of the filovirus
genome whose expression is known to interfere with the assembly of Ebolavirus-
adaptation?
 phylogenetic evidence strongly indicated that the direction of transfer was from
virus to mammal. Eutherians other than bats, rodents, and insectivores (i.e., the
candidate reservoir taxa for filoviruses) were significantly underrepresented
 existence of orthologous filoviruslike elements among mammalian suggests that
filoviruses are at least tens of millions of years old (based on mammalian lineage
age estimates).
 filovirus infections have been recorded as paleoviral elements in the genomes of
small mammals despite extranuclear replication and a requirement for cooption of
reverse transcriptase.
Genomic surveillance elucidates Ebola virus origin and transmission during the 2014
outbreak
Gire et al.
Science (345), 2014
https://science.sciencemag.org/content/345/6202/1369
 Gire et al. describe Ebola epidemiology on the basis of 99 whole-genome
sequences, including samples from 78 affected individuals. (2000x coverage)
 observed a rapid accumulation of interhost and intrahost genetic variation,
allowing us to characterize patterns of viral transmission over the initial weeks of
the epidemic
 Outbreak started from single transmission event from unknown animal reservoir
into human populations.
 Two viral lineages from Guinea then spread from person-to-person in Sierra Leone
 many of the mutations alter protein sequences and other biologically meaningful
targets
 Deep-sequence coverage allowed identification of 263 iSNVs (73
nonsynonymous, 108 synonymous, 70 noncoding, and 12 frameshift) in the
Sierra Leone patients. One notable intrahost variation is the RNA editing site
of the glycoprotein (GP) gene
 rooting the tree on the oldest outbreak reveals a strong correlation between
sample date and root-to-tip distance, with a substitution rate of 8 × 10−4 per
site per year. Suggests lineages of three most recent outbreaks all diverged
from a common ancestors at roughly the same time (2004)
 supports the hypothesis that each outbreak represents an independent
zoonotic event from the same genetically diverse viral population in its
natural reservoir
 One iSNV (position 10,218) shared by 12 patients is later observed as fixed
within 38 patients, becoming the majority allele in the population
 Repeated propagation at intermediate frequency suggests that transmission
of multiple viral haplotypes may be common.
 The observed substitution rate is roughly twice as high within the 2014
outbreak as between outbreaks. Mutations are also more frequently
nonsynonymous during the outbreak
 consistent with expectations from incomplete purifying selection
Temporal and spatial analysis of the 2014–2015 Ebola virus outbreak in West Africa
Carroll et al.
Nature (524), 2015
https://www.nature.com/articles/nature14594.pdf

Ebola Virus Epidemiology, Transmission, and Evolution during Seven Months in Sierra
Leone
Part et al.
Cell 161. 2015
https://www.sciencedirect.com/science/article/pii/S009286741500690X
Reduced evolutionary rate in reemerged Ebola virus transmission chains
Blackley et al.
Science Advances (2), 2016
https://advances.sciencemag.org/content/2/4/e1600378/tab-pdf
Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013–2016 Epidemic
Diehl et al
Cell (167-4), 2016
https://www.sciencedirect.com/science/article/pii/S0092867416313976
Human Adaptation of Ebola Virus during the West African Outbreak
Cell, Volume 167, 2016
https://www.sciencedirect.com/science/article/pii/S0092867416313964
Did a Single Amino Acid Change Make Ebola Virus More Virulent?
Cell, Volume 167, 2016
Bedford and Malik
https://www.sciencedirect.com/science/article/pii/S0092867416314520
Comment on “Mutation rate and genotype variation of Ebola virus from Mali case
sequences”
Rambaut et al
Science, 353, 2016
https://science.sciencemag.org/content/353/6300/658.1
Real-time, portable genome sequencing for Ebola surveillance
Quick et al.
Nature (530), 2016
https://www.nature.com/articles/nature16996.pdf
The evolution of Ebola virus: Insights from the 2013–2016 epidemic
Holmes et al.
Nature (538), 2016
https://www.nature.com/articles/nature19790.pdf
Virus genomes reveal factors that spread and sustained the Ebola epidemic
Dudas et al.
Nature (544), 2017
https://www.nature.com/articles/nature22040.pdf
Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors
Whitmer et al
Cell, 22, 2018
https://www.sciencedirect.com/science/article/pii/S2211124718300081
Distinct Genome Replication and Transcription Strategies within the Growing Filovirus
Family
Hume and Muhlberger
Journal of Molecular Biology, Available online 2019
https://www.sciencedirect.com/science/article/pii/S0022283619304188
Response to Comment on “Mutation rate and genotype variation of Ebola virus from Mali
case sequences”
Hoenen et al. Science, 353, 2012
https://science.sciencemag.org/content/353/6300/658.2.full