Phylogeny and COVID-19 The Origins of SARS-CoV-2and coronavirus from Palm Civets . Song et al., PNAS...
Transcript of Phylogeny and COVID-19 The Origins of SARS-CoV-2and coronavirus from Palm Civets . Song et al., PNAS...
Phylogeny and COVID-19 The Origins of SARS-CoV-2
ICAP Columbia University, July 22, 2020
Bette KorberLos Alamos National Laboratory
What is a phylogenetic tree?Greek: φῦλον (phûlon), meaning "lineage", and γένεσις (génesis), meaning "origin"
Darwin gets credit for the first one
The relationship between SARS-CoV-1 outbreaksand coronavirus from Palm Civets Song et al., PNAS 102:2430 (2005)
Human, 2002/3
Palm Civet 03Human, 2003/4, GZ
Palm Civet 04, GZ
Common Ancestor
GZ: Guangzhou con
SZ: Shenzhen con
ZS: Zhongshan con
BL1
BL2
BL = Branch length
BL2 reflect the genetic distance from the HP04 leaf to the ancestral nodeBL1+BL2 ~ the genetic distance between PC04 and HP04
What can you learn in glance? HP04’s virus is more closely related to the contemporary Palm Civet, than the virus in people from the year before
Coronavirinae subfamily: 4 genera, RdRpRNA dependent RNA polymerase
Photo credit: Jessicajil
Betacoronavirus
Sarbecovirus
Merbecovirus
From Cui, Li, & Shi, Nature Rev Microbio 17:181 (2019)Origin and evolution of pathogenic coronaviruses
Highly pathogenic in human
Common Cold in human
Common Cold in human
Bats worldwide are a reservoir of highly diverse Alphacoronaviruses and Betacoronaviruses.
2002, 8,098 cases, 9.5% fatal
2012, 2,260 cases, 35.5% fatal
GZ: Guangzhou con
Human, 2002/3Photo credit: Praveenp cc
SZ: Shenzhen conZS: Zhongshan con
Palm Civet
Palm Civet 03Human, 2003/4, GZ
Palm Civet 04, GZ
Horseshoe Bat, reservoir
The relationship between SARS-CoV-1 outbreaksand coronavirus from Palm Civets Song et al., PNAS 102:2430 (2005)
Minor outbreak in Guangzhou markets, Palm Civet -> human
Human, SARS-CoV91 sequences
Recombination is a very important aspect of coronavirus evolution.
Here is a simple example from SAR-CoV-2.
EPI ISL 422850
SARS-CoV-2 sequences from the Netherlands
What do we know about how SARS-CoV-2 evolved and made the jump into humans?
Emergence of SARS-CoV-2 through recombination and strong purifying selection Xiaojun Li, Elena E. Giorgi, Manukumar Honnayakanahalli Marichannegowda, Brian Foley2, ChuanXiao3, Xiang-Peng Kong4, Yue Chen1, S. Gnanakaran2, Bette Korber, Feng Gao
Science Advances, 6:27 eabb9153 (Jul1, 2020)
Maximum likelihood tree, 1000 bootstraps
Sarbecovirus Full Genome tree:
Here we just confirm that Bat RaTG13 isMost closely related to SARS-CoV2 overall.
A pneumonia outbreak associated with a new coronavirusof probable bat origin. Zhou et al. Nature 579, 270–273 (2020)
SARS-CoV2 and SARS-CoV: 79.6% sequence identity
SARS-CoV2 and Bat SL-CoV_RaTG1396.2% sequence identity
Bat SL-CoV_RaTG13:From Rhinolophus affinis from Yunnan province, 2013
2005, Zhejiang China
Guangdong China
Guangxi China
Simplot Analysis Compared to the SARS-CoV-2 Reference strain
Usually closest to RaTG13, but not always.
Full Genome
Bat
Pangolin
RIP analysis comparing Bat RaTG13 and Pangolin GD/P1
Very extensive recombination among Bat and Pangolin sequences in these regions
Very extensive recombination among Bat and Pangolin sequences in these regions
Very extensive recombination among Bat and Pangolin sequences in these regions
The key ACE2 contact residues in SARS-CoV-2match Pangolin P1La
Bat CoVs with large deletions in the ACE2 RBD of the Spike do not infect human cells
Although SARS-CoV-2 and SARS-CoV are very divergent in the ACE2 RBD, they are conformationally highly similar
ACE2
S1 SARS CoVS1 SARS CoV-2
Strong purifying selection with in Group Ain Spike:
SARS COV-2RaTG13Pangolin
Very little nonsynonymous changeExtensive synonymous change
Regi
ons o
f Pur
ifyin
g Se
lect
ion
Simplot showing recombination also played a role in SARS-CoV-1/bat virus evolution
Conclusions
The more efficient cleavage of S1 and S2 subunits of the S glycoprotein and more efficient bindingto ACE2 by SARS-CoV-2 may have allowed SARS-CoV-2 to jump to humans, leading to the rapid
pandemic spread of SARS-CoV-2.
1) Recombination among sarbecoviruses is a very common and critical evolutionary mechanism
2) It is likely that the acquisition of a complete functional RBM by a RaTG13-like CoVthrough a recombination event with a Pan_SL-CoV_GD–like virus enabled SARS-CoV-2 to efficiently use ACE2, thus enabling human infection.
3) SARS-CoV-2 has a unique furin cleavage site insertion (PRRA) not found in Sarbecovirus group, although similar motifs are found in MERS and more divergent bat CoVs, making S1/S2 cleavage in SARSCoV-2 more efficient than in SARS-CoV
Coutard, Antivir Res 176: 104742 (2020)Walls, Cell 180, 281–292.e6
Emergence of SARS-CoV-2 through recombination and strong purifying selection Xiaojun Li, Elena E. Giorgi, Manukumar Honnayakanahalli Marichannegowda, Brian Foley2,
Chuan Xiao3, Xiang-Peng Kong4, Yue Chen1, S. Gnanakaran2, Bette Korber, Feng Gao
Science Advances, 6:27 eabb9153 (Jul1, 2020)