WUHAN COVID-19 SYNTHETIC ORIGINS AND EVOLUTION

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DOI: 10.5281/zenodo.3724003
Cite this publication
Abstract
The main result of this updated release is the formal proof that 2019-nCoV coronavirus is partially a SYNTHETIC genome. We proof the CONCENTRATION in a small région of wuhan New genome (300bp) of 3 different régions from HIV1 ENVELOPPE gene and 3 others from HIV2 and SIV (ENV and POL RT). All this is remarkable and bears the mark of a desire for organization of a human nature: LOGIC, SYMETRIES. In this article, we demonstrate also that there is a kind of global human hosts adaptation strategy of SARS viruses as well as a strategy of global evolution of the genomes of the different strains of SARS which have emerged, mainly in China, between years 2003 first SARS genomes and the last 2019 COVID-19 Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete genome. This global strategy, this temporal link, is materialized in our demonstration by highlighting stationary numerical waves controlling the entire sequence of their genomes. Curiously, these digital waves characterizing the 9 SARS genomes studied here are characteristic whole numbers: the "Fibonacci numbers", omnipresent in the forms of Nature, and which our research for several decades has shown strong links with the proportions of nucleotides in DNA. Here we demonstrate that the complexity and fractal multiplicity of these Fibonacci numerical waves increases over the years of the emergence of new SARS strains. We suggest that this increase in the overall organization of the SARS genomes over the years reflects a better adaptation of SARS genomes to the human host. The question of a link with pathogenicity remains open. However, we believe that this overall strategy for the evolution of the SARS genomes ensures greater unity, consistency and integrity of the genome. Finally, we ask ourselves the question of a possible artificial origin of this genome, in particular because of the presence of fragments of HIV1, HIV2 and SIV retroviruses.
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Science
WUHAN COVID-19 SYNTHETIC ORIGINS AND EVOLUTION
Jean-Claude PEREZ *1
*1 Phd Maths & Computer Science Bordeaux University, RETIRED Interdisciplinary Researcher
(IBM Emeritus, IBM European Research Center on Artificial Intelligence)
Abstract
The main result of this updated release is the formal proof that 2019-nCoV coronavirus is partially
a SYNTHETIC genome. We proof the CONCENTRATION in a small région of wuhan New
genome (300bp) of 3 different régions from HIV1 ENVELOPPE gene and 3 others from HIV2
and SIV (ENV and POL RT). All this is remarkable and bears the mark of a desire for organization
of a human nature: LOGIC, SYMETRIES.
In this article, we demonstrate also that there is a kind of global human hosts adaptation strategy
of SARS viruses as well as a strategy of global evolution of the genomes of the different strains of
SARS which have emerged, mainly in China, between years 2003 first SARS genomes and the
last 2019 COVID-19 Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1, complete
genome.
This global strategy, this temporal link, is materialized in our demonstration by highlighting
stationary numerical waves controlling the entire sequence of their genomes.
Curiously, these digital waves characterizing the 9 SARS genomes studied here are characteristic
whole numbers: the "Fibonacci numbers", omnipresent in the forms of Nature, and which our
research for several decades has shown strong links with the proportions of nucleotides in DNA.
Here we demonstrate that the complexity and fractal multiplicity of these Fibonacci numerical
waves increases over the years of the emergence of new SARS strains.
We suggest that this increase in the overall organization of the SARS genomes over the years
reflects a better adaptation of SARS genomes to the human host.
The question of a link with pathogenicity remains open.
However, we believe that this overall strategy for the evolution of the SARS genomes ensures
greater unity, consistency and integrity of the genome.
Finally, we ask ourselves the question of a possible artificial origin of this genome, in particular
because of the presence of fragments of HIV1, HIV2 and SIV retroviruses.
Keywords: SARS; Wuhan COVID-19; Fibonacci Numbers; Fractal Genome; Numerical
Stationary Periodic Waves; HIV1; HIV2; SIV; Synthetic Genomes.
Cite This Article: Jean-Claude PEREZ. (2020). WUHAN COVID-19 SYNTHETIC ORIGINS
AND EVOLUTION.” International Journal of Research - Granthaalayah, 8(2), 285-324.
https://doi.org/10.5281/zenodo.3724003.
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1. Introduction
“Where there is matter, there is geometry.” - Johannes Kepler
Since the SARS coronavirus emergence 18 years ago, a large number of severe acute respiratory
syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural host, bats.
Some of those bat SARSr-CoVs have the potential to infect humans. In january 2020, Wuhan
China megacity was the origin of a Novel SARS disease entitled by OMS « COVID-19 » [6]. This
novel coronavirus (COVID-19) caused an epidemic of respiratory syndrome in humans, in Wuhan,
China then in other World countries (Iran South Korea, Italia...). As show in the following figures,
we analyse in this article 9 whole SARS genomes with the goal to discover a possible strategy of
SARS GENOMES EVOLUTION from 2003 original viruses to the 2020 WUHAN virus.
Figure 1: From Ncbiinsights 2020. Coloured References are our 9 Analysed SARS/Wuhan
Genomes.
Secondly, for about 30 years, we have been looking for possible global, even digital, structures
that would organize DNA, genes, chromosomes, and even whole genomes [27, 28, 30, 50, 51].
however, it is only by deepening the notion of "fractal periodicity", outlined in [7, 38], and we will
highlight here that we have re-discovered the major role of Fibonacci fractal stationary waves
at both scales of each whole individual chromosomes and whole genome. We then demonstrate a
sort of "hierarchical classification" of the 24 chromosomes. In this hierarchy, the chromosome4
seems to play a major and privileged role.
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By comparing chromosome, the 3 reference genomes of Neanderthal, Sapiens BUILD34 of 2003
and Sapiens HG38 of 2013, we demonstrate the evidence of « fractal periods » and « Resonance
periods» characterizing each of the 24 human chromosomes [47]. As illustrated in Figure1 below,
these resonances make it possible to differentiate the respective genomes of Neanderthal and
Sapiens on the global scale of the chromosome (here chromosome 4). Here, a resonance of 34
nucleotides is common to both chromosomes 4 of Sapiens and Neanderthal, however, the
respective forms of these resonance curves are radically different.
Figure 2: As will be demonstrated here, the 2 respective Chromosomes 4 of Neanderthal and
Sapiens HG38 share a "resonance" of 34 bp, however, these two radically different resonance
curves illustrate a major differentiation of the 2 human species at the GLOBAL scale of
chromosome 4.
2. Methods
The 9 Analysed Genomes:
SARS2003 SARS Coronavirus SZ16, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/Ay304488
SARS2004 Bat SARS Coronavirus Rm1, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/DQ412043
SARS2004b SARS Coronavirus ZS-C, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/AY395003
SARS2012 Bat SARS-Like Coronavirus Isolate Rs4084, Complete Genome -
Nucleotide - NCBI. Ky417144.1
https://www.ncbi.nlm.nih.gov/nuccore/KY417144.1
SARS2015 Bat SARS-Like Coronavirus Isolate Bat-SL-Covzxc21, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/Mg772934
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SARS2017 Bat Sars-Like Coronavirus Isolate Bat-Sl-Covzc45, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/Mg772933
WUHANOLD (first genome sequenced 12 January 2020) Wuhan Seafood Market
Pneumonia Virus Isolate Wuhan-Hu-1, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/MN908947.1
WUHAN2 (second improved sequenced genome 14 January 2020) Wuhan Seafood
Market Pneumonia Virus Isolate Wuhan-Hu-1, Complete Genome Genbank:
MN908947.2
https://ncbiinsights.ncbi.nlm.nih.gov/2020/01/13/novel-coronavirus/
https://www.ncbi.nlm.nih.gov/nuccore/MN908947.3?report=fasta
WUHAN (23 January 2020) Wuhan Seafood Market Pneumonia Virus Isolate Wuhan-
Hu-1, Complete Genome GenBank: MN908947.3
https://www.ncbi.nlm.nih.gov/nuccore/MN908947.3
Computing Fractal Periods and Resonances Summary
The complete description of this method can be found in [47], Six Fractal Codes of Biological
Life: perspectives in Exobiology, Cancers Basic Research and Artificial Intelligence Biomimetism
Decisions Making. Preprints 2018, 2018090139 (doi: 10.20944/preprints201809.0139.v1).
https://www.preprints.org/manuscript/201809.0139/v1
We introduce here a method of global analysis of the roughness or fractal texture of the DNA
sequences at the chromosome scale. To do this, we generalize the method of numerical analysis of
the "Master Code of Biology" [39-42, 44]. Thus, we restructure the sequence into different generic
sequences based on "meta codons" no longer triplets of 3 nucleotides but values ranging from 17
to 377 nucleotides, i.e 360 simulations. This method of analysis will then reveal, in most cases,
discrete waves or interferences, most often dissonances. However, sometimes there will emerge
kinds of resonances where all scales of analysis appear to be in symbiosis.
Function: The Genomics master code (-II-) is generalized to meta-codons that no longer have 3
nucleotides as a codon, but 4, 5, ... 377 nucleotides. Then we analyze the textures by the undulatory
code (-IV-). It then appears dissonances and resonances that will reveal periods of discrete waves,
resonances, and standing waves. The Genomics Binary code analysis (-III-) confirms these periods
using a complementary independent method.
Inputs: Double strand DNA sequence Pi-mass grouped by meta-codons (each Pi-mass is = -1
times number of « G » bases in meta-codon double strand or also = -1 times number of « C+G »
bases in single strand meta-codon.
Outputs: Period and resonance standing wave computed by two complementary methods.
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Summary: We introduce here a method of global analysis of the roughness or fractal texture of
the DNA sequences at the chromosome scale. To do this, we generalize the method of numerical
analysis of the "Master Code" [47 -II- ]. Thus, we restructure the sequence into different generic
sequences based on "meta codons", no longer triplets of 3 nucleotides, but values ranging from 17
to 377 nucleotides, ie 360 simulations. This method of analysis will then reveal, in most cases,
discrete waves or interferences, most often dissonances (based on Genomics Undulatory waves
described here in [47 -II- ]. However, sometimes there will emerge kinds of resonances where all
scales of analysis appear to be in symbiosis.
Process: The discrete interferences fields resulting from the analysis of an entire chromosome are
therefore a three- dimensional space: Dim y (vertical) restructuring in meta codons of lengths 17
to 377 nucleotides (or in this Coronavirus article meta codons 1bp to 100bp) Dim x (horizontal)
Leibnitz differentiations such that primary 1/2 secondary 1/3... 1/4 ... 1 / n Dim z cumulated
populations from the "Master code" operators. The + 1 / -1 derivatives will be of type increase, ie
+1 if derivative increasing and will be of type decrease, ie -1 if derived decreasing. In this context
we will explore these 3D spaces in 2 forms:
Horizontally [47 -IV-], meta codons dimension: curves for a given meta codon dimension,
see in the example "resonances" below (see Figure 3 and Figure 4).
Vertically [47 -III-], spectral differentiation: discrete series d2-d1 is +1 if increase and -1
if decrease (see Figure 5). We represent in top the +1 and in low the -1, (see Figure 5).
Table 1: Computing the periodic standing waves and resonances for various metacodons
Genomics Master code.
Dim x d1 d2 …/... d100
Dim y
…/... 377
Horizontal scan: exp. meta codons of 22 bases: 22 761233 774174 779102 783714 786854 …/...
(see Figure 3)
Vertical scan example derivations of first order: 1 if d2>d1 and -1 if d2<d1 then: -1 1 -1 1 -1 1 1 -
1 1 -1 1 1 …/... (see Figure 4 and Figure 5).
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Figure 3: Zoom on Vertical Scan Method Revealing PERIOD = 22 From HG38 Reference
Chromosome21.
These two independent methods lead in all the cases analyzed to the same period value: here, for
example, the period "horizontal scan" is a resonance of 22bp (Figure 4) and the period "vertical
scan" is a period of repeatability of 22bp also (Figure 5).
Figure 4: Evidence of a resonance of 22bp period in the whole HG38 human reference
chromosome21.
(see Figure 4 and Figure 5), [47 -IV-].
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Figure 5: Confirmation of a 22bp period in the whole HG38 human reference chromosome21 [47
-IV-].
A third complementary method is presented here: knowing the period determined and confirmed
by the two previous methods, we segment the complete sequence of the chromosome by
consecutive segments according to this period, for example here for the chromosome21, we will
"cut" the entire sequence of the chromosome in successive sections of 22 bases, the length of the
period discovered. Then we record for each segment the C + G populations on the one hand and T
+ A on the other hand. We then represent the cumulative distribution curve of these different CG
and TA populations throughout the chromosome sequence.
We then represent the cumulative distribution curve of these different CG and TA populations
throughout the chromosome sequence (Table2).
Table 2: This table shows a C+G top for 8 bases value within 22 bases segments distribution.
7
8
9
205735
230173
219804
46083
75340
106183
The Figure 6 shows a C+G top for 8 bases value within 22 bases segments distribution.
segmented by 22 bases periods.
Figure 6: Gauss like CG / TA distribution within the whole human HG38 chromosome21.
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3. Results and Discussion
SARS2003
SARS Coronavirus SZ16, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/Ay304488
Figure 7: Stationary wave 5bp ON
Figure 8: Stationary wave 8bp OFF
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Figure 9: Stationary wave 13bp OFF
Figure 10: Stationary wave 21bp OFF
In this initial SARS2003 genome, we find only the Fibonacci stationary wave 5bp (Figure 7). All
other fractal waves 8,13, 21 bp are absent.
SARS2004
Bat SARS coronavirus Rm1, complete genome
https://www.ncbi.nlm.nih.gov/nuccore/DQ412043
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Figure 11: Stationary wave 5bp ON
Figure12: Stationary wave 8bp OFF
Figure 13: Stationary wave 13bp OFF
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Figure 14: Stationary wave 21bp OFF
In this second SARS2004 genome, we find only the Fibonacci stationary wave 5bp (Figure 11).
All other fractal waves 8,13, 21 bp are absent.
SARS2004b
SARS Coronavirus ZS-C, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/AY395003
Figure 15: Stationary wave 5bp ON
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Figure 16: Stationary wave 8bp OFF
Figure 17: Stationary wave 13bp OFF
Figure 18: Stationary wave 21bp OFF
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In this third SARS2004b genome, we find only the Fibonacci stationary wave 5bp (Figure 15). All
other fractal waves 8,13, 21 bp are absent.
SARS2012
Bat SARS-Like Coronavirus Isolate Rs4084, Complete Genome - Nucleotide - NCBI.
Ky417144.1
https://www.ncbi.nlm.nih.gov/nuccore/KY417144.1
Figure 19: Stationary wave 5bp ON
Figure 20: Stationary wave 8bp OFF
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Figure 21: Stationary wave 13bp OFF
Figure 22: Stationary wave 21bp OFF
In this fourth SARS2012 genome, we find only the Fibonacci stationary wave 5bp (Figure 19). All
other fractal waves 8,13, 21 bp are absent.
SARS2015
Bat SARS-Like Coronavirus Isolate Bat-SL-Covzxc21, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/Mg772934
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Figure 22: Stationary wave 5bp ON
Figure 23: Stationary wave 8bp ON
Figure 24: Stationary wave 13bp ON
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Figure 25: Stationary wave 21bp OFF
In this fifth SARS2015 genome, we find now three Fractal Fibonacci stationary wave 5bp, 8bp,
and 13bp (Figures 21, 22, 23). Meanwhile the fourth other fractal wave 21 bp remain absent.
SARS2017
Bat SARS-Like Coronavirus Isolate Bat-SL-Covzc45, Complete Genome
https://www.ncbi.nlm.nih.gov/nuccore/Mg772933
Figure 26: Stationary wave 5bp ON
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Figure 27: Stationary wave 8bp ON
Figure 28: Stationary wave 13bp ON
Figure 29: Stationary wave 21bp OFF
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In this sixth SARS2017 genome, we find also three Fractal Fibonacci stationary wave 5bp, 8bp,
and 13bp (Figures 26, 27, 28). Meanwhile the fourth other fractal wave 21 bp remain absent.
WUHANOLD (first genome sequenced 12 january 2020) Wuhan seafood market pneumonia
virus isolate Wuhan-Hu-1, complete genome MN908947.1
https://www.ncbi.nlm.nih.gov/nuccore/MN908947.1
Figure 30: Stationary wave 5bp ON
Figure 31: Stationary wave 8bp ON
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Figure 32: Stationary wave 13bp ON
Figure 33: Stationary wave 21bp ON
In this seventh WUHANOLD 12 January 2020 genome, we find also three Fractal Fibonacci
stationary wave 5bp, 8bp, and 13bp (Figures 29, 30, 31). Now the fourth other fractal wave 21 bp
is also present (Figure 33).
WUHAN2 (second improved sequenced genome 14 January 2020) Wuhan seafood market
pneumonia virus isolate Wuhan-Hu-1, complete genome GenBank: MN908947.2
https://ncbiinsights.ncbi.nlm.nih.gov/2020/01/13/novel-coronavirus/
https://www.ncbi.nlm.nih.gov/nuccore/MN908947.3?report=fasta
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Figure 34: Stationary wave 5bp ON
Figure 35: Stationary wave 8bp ON
Figure 36: Stationary wave 13bp ON
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Figure 37: Stationary wave 21bp ON
In this eighth WUHAN2 14 January 2020 genome, we find also three Fractal Fibonacci stationary
wave 5bp, 8bp, and 13bp (Figures 33, 34, 35). Now the fourth other fractal wave 21 bp is also
present (Figure 36).
WUHAN (23 January 2020) Wuhan seafood market pneumonia virus isolate Wuhan-Hu-1,
complete genome GenBank: MN908947.3
https://www.ncbi.nlm.nih.gov/nuccore/MN908947.3
Figure 39: Stationary wave 5bp ON
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Figure 40: Stationary wave 8bp ON
Figure 41: Stationary wave 13bp ON
Figure 42: Stationary wave 21bp ON
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In this last and ninth reference WUHAN 23 January 2020 genome, we find also three Fractal
Fibonacci stationary wave 5bp, 8bp, and 13bp (Figures 39, 40, 41). Now the fourth other fractal
wave 21 bp is also present (Figure 42).
Figure 43: A second method of highlighting the standing wave of period 21bp.
4. Conclusions and Recommendations
Table 3 below clearly demonstrates a kind of evolution of SARS genomes between 2003 and 2020.
If it remains difficult to associate this evolution with an increase in pathogenicity for humans, data
already published by us [44-46] rather would suggest a greater ADAPTABILITY of these genomes
to the human host genome by the same coherence and united via standing waves of Fibonacci [37].
Table3: High level of correlation between the years of emergence of the SARS virus and the
presence of Fibonacci fractal standing waves.
NCBI reference
Length
bp
Fibonacci numbers FRACTAL
embedded stationary waves periods
5bp
8bp
13bp
21bp
34bp
AY304488
29731
Yes
DQ412043
29749
Yes
AY395003
29647
Yes
KY417144.1
29770
Yes
MG772934
29732
Yes
Yes
Yes
MG772933
29802
Yes
Yes
Yes
MN908943.1
30473
Yes
Yes
Yes
Yes
MN908943.2
29875
Yes
Yes
Yes
Yes
MN908943.3
29903
Yes
Yes
Yes
Yes
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Deleting region
in MN908943.3
29153
Yes
Yes
Yes
Yes
Yes
In figure 44 we have superimposed the standing waves of 21bp corresponding to the 3 published
versions of the wuhan genome of 2020. There appears a very high sensitivity, which suggests the
fact that this new genome is in full phase of evolution in its adaptation to the human host. the 3
figures 33, 37, 42 show this evolution better: WUHANOLD: 3.5 waves, WUHAN2: one and
epsilon wave, WUHAN: 2 waves.
Figure 44: High level of sensitivity for 3 releases of Wuhan CoV-2019 genomes of almost
identical lengths (30473, 29875 and 29903bp).
How Could Tomorrow 2019-Ncov Evolve?
In [2] and [5], authors show that there is no doubt that 2019-nCoV is a novel unknown sequence.
In an unformal draft, Dr Lyons-weiler [4] even suggests that a region between the bases 21600-
22350 bp would be completely new. Considering that this region could be "foreign" to the family
of coronaviruses we tried to test how its absence could have had an impact on the waves that we
reveal here. We then construct a hypothetical genome which would no longer have this insertion
between the bases 21600-22350 bp. It then appears (Figure 45), for the first time a Fibonacci wave
of 34bp. This genome would therefore be structured by a fractal nesting of 5 Fibonacci waves, 5 8
13 21 and now 34bp. Curiously, we have only encountered such a level of organization in the
entire human chromosome4 (figure 46). A new question: "Can there be some kind of affinity
between the waves of a retrovirus and the human host genome in which this retrovirus could
integrate?"
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Figure 45: Standing wave 34bp structuring modified 2019-NCoV genome.
Figure 46: Standing wave 34bp overlapping the whole human chromosome4 (from [43]).
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On A Possible "Harmonic Standing Wave Agreement" Between the Human Host
Chromosome and The Coronavirus Retrovirus:
This last observation opens here an interesting theoretical track on 2 possible strategies of
integration of retroviruses in eucharyotic chromosomes:
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1 / symbiosis strategy by complementarity: example of HIV more frequently integrating
chromosomes 20 16 17 22 19. These chromosomes have a poor HGO (Human Genome Optimum)
ratio, it will be slightly improved by the integration of the virus.
Indeed, in [8, 46], we demonstrated why the permeability to the integration of retrovirus in each
of our chromosomes is correlated with this classification HGO (HUMAN GENOME OPTIMUM)
of this article http://www.imedpub.com/abstract/towards-a-universal-law-controlling-all-human-
cancer-chromosome-loh-deletions-perspectives-in-prostate-and-breast-cancers-screening-
20846.html
For example, chromosomes 20. 16. 17. 22 19 are very permeable: this table shows that they are
located at the bottom of this table of classification of HGOs of 24 human chromosomes.
Table 3: HGO human chromosomes classification.
https://juniperpublishers.com/ctoij/images/CTOIJ.MS.ID.555756.T001.png
We also see in figure 47 from Figure 4 (Wang 2007), that these chromosomes are very permeable
to the HIV retrovirus (Dark green bands in the following image from [3].
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Figure 47: from [3] Green regions are retoviruses integration region,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3385939/figure/A006890F4/
2 / symbiosis strategy by wave agreement, resemblance: this could be the case of the coronavirus
which would integrate by a kind of harmonic agreement to chromosomes 4 or 13, located at the
beginning of the HGO table, which have like it Fibonacci waves . This would hardly affect the
resulting HGO ratio, or even strengthen it: This is surely the case with RETROTRANSPOSONS.
Finally, we have recognized here 2 laws of symbiosis of nature: agreement because very
DIFFERENT, and agreement because very SIMILAR.
Strategies that we find up to the affinities between humans ...!!!
If the genome of the 2019-nCoV retrovirus has adopted this second strategy of integration into the
human genome, this could explain the fact observed at the beginning of 2020: a moderately
pathogenic virus but which spreads very quickly ... Because its retrovirus would be judiciously
adapted to its (supposed) host chromosome4 of the human genome?
On A Possible Origin Of 2019-Ncov Genome:
It is very likely that there was HUMAN INTERVENTION in this LYONS's region [4] of wuhan
genome:
Analysis of this region in all coronaviruses shows a 100% jump in homology for the Wuhan
genomes and 70 to 80% for the closest SARS. Although there is already a trace of ENV HIV1 in
the genome that we have referenced here SARS2003.
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While there is NO TRACE of HIV1 ENV in the region (Lyons-weiler 20020) in all other SARS
Coronavirus genomes, Indeed, we find on a mini region (243-86bp = ~ 160bp) 3 partial regions of
ENV HIV1 which are all 3 "DIFFERENT" and from 3 different HIV1 strains:
COVID-19 (86-113) ==> in ENV HIV1: 1201 <==> 1228.
COVID-19 (213-244) ==> in ENV HIV1: 424 <==> 394.
COVID-19 (243-281) ==> in ENV HIV1: 1064 <==> 1029.
in ENV HIV1 Here, these 3 regions, while hyper compressed in Lyons wuhan (<200bp), they are
more widely spaced in hiv1 env (394 <==> 1228), ie> 830bp.??? HOW TO EXPLAIN THIS
CONCENTRATION OF 3 SEQUENCES ENV HIV1???? IF NOT BY HUMAN ACTION?!!!!
Then, in a second time, we discovered 3 other regions from HIV2 and SIV...
See details and Blast proves here:
Location of the 300 first bp in [4] from wuhan COVID-19 reference genome (starting from bp
21672).
Wuhan seafood market pneumonia virus genome assembly, chromosome: whole_genome
Sequence ID: LR757998.1 Length: 29866Number of Matches: 1
Range 1: 21672 to 21971GenBankGraphicsNext Match Previous Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
555 bits(300)
2e-158
300/300(100%)
0/300(0%)
Plus/Plus
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Details:
Region HIV1a 86-113:
HIV-1 isolate 19663.24H9 from Netherlands envelope glycoprotein (env) gene, complete cds
Sequence ID: GU455503.1Length: 2598Number of Matches: 1
Range 1: 1201 to 1228 GenBankGraphics Next Match Previous Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
38.3 bits(41)
1.9
25/28(89%)
0/28(0%)
Plus/Plus
Region HIV1b 213-244:
HIV-1 isolate 4045_Plasma_Visit1_amplicon5a from Malawi envelope glycoprotein (env) gene,
complete cds
Sequence ID: KC187063.1Length: 2547Number of Matches: 1
Range 1: 394 to 424GenBankGraphics Next Match Previous Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
37.4 bits(40)
7.1
28/32(88%)
1/32(3%)
Plus/Minus
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Region HIV1c 243-281:
HIV-1 isolate 07.RU.SP-R497.VI.G3 from Russia envelope glycoprotein (env) gene, complete
cds
Sequence ID: GU481453.1Length: 2580Number of Matches: 1
Range 1: 1029 to 1064GenBankGraphicsNext Match Previous Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
38.3 bits(41)
7.1
32/39(82%)
3/39(7%)
Plus/Minus
Region HIV2a 24-43:
HIV-2 isolate 106CP_RT from Cote d'Ivoire reverse transcriptase gene, partial cds
Sequence ID: KJ131112.1Length: 924Number of Matches: 1
Range 1: 66 to 85GenBankGraphicsNext MatchPrevious Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
32.8 bits(35)
0.38
19/20(95%)
0/20(0%)
Plus/Minus
Region HIV2b 133-158:
Human immunodeficiency virus type 2 complete genome from strain HIV-2UC1
Sequence ID: L07625.1Length: 10271Number of Matches: 1
Range 1: 6701 to 6726GenBankGraphics Next Match Previous Match
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Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
30.1 bits(32)
1.3
22/26(85%)
0/26(0%)
Plus/Plus
Region SIVa 270-299:
Simian immunodeficiency virus partial pol gene for Pol, isolate SIVagmTAN-CM545-pol
Sequence ID: LM999945.1Length: 3111Number of Matches: 1
Range 1: 1069 to 1098GenBankGraphics Next Match Previous Match
Alignment statistics for match #1
Score
Expect
Identities
Gaps
Strand
32.8 bits(35)
4.2
25/30(83%)
0/30(0%)
Plus/Minus
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To Conclude:
Figure 48: Double level of correlation between the years of emergence of the SARS virus, the
presence of standing Fibonacci fractal waves, and the Fractal number of nested and embedded
Fibonacci layers.
One track that will need to be deepened is that of integrating the SARS coronavirus genome into
human chromosomes [9, 57].
Indeed, if we show that each of the 24 human chromosomes is characterized by one or more
specific standing waves, some of our chromosomes (chromosomes 4 and 13 for example) have
standing waves which are Fibonacci numbers [7]. There could then be a kind of harmonic
agreement between the genome of the SARS virus and its human host chromosome, both of which
have standing Fibonacci waves, which will facilitate and strengthen the integration and persistence
of these viruses in humans.
Finally, That is a formal proof of an evolution increasing global structure of SARS whole genomes,
probably linked with genome integrity and coherence and, human génome adaptation [8, 38] ,
perhaps pathogenicity.
Evidence of A Kind of "Intelligent Will" ...
Please, now, see figures 49 then 50.
Both figures proves evidence that the 6 HIV/SIV inserts are not the result of natural evolution and
mutations.
Particularly,
Firstly, the 6 inserts are highly contiguous: 169bp within 275bp regions.
Secondly, HIV/SIV inserted strains are very homogeneous: Russia, Cote d'ivoire,
Netherlands, Malawi origins.
Thirdly, the functions of inserts are also various: 2 from POL/RT, 4 from ENVELOPPE
functional genes.
Not reported in this article, wz found also within the COVID-19 genome 3 others HIV/SIV
regions: one from ENVELOPPE, one from RT, and one from INTEGRASE.
POL/RT, INTEGRASE, and ENVELOPPE: we have here 3 majors functional pieces of
genes necessary to build a retrovirus...
In other hand,
1 / SYMMETRY: strategy of realism (numbers of inserts by increasing frequencies and
pathogenicity):
1 SIV
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2 HIV2
3 HIV1
2 / SYMMETRY: economy strategy (sense and antisense in an insert of minimum length):
Hiv2a. <---
Hiv1a. --->
Hiv2b --->
Hiv1b <---
HIV1c <---
Siva --->
3 / SYMETRY: Symmetry Pol / ENV
The 6 inserts are positioned in this order in Covid-19
RT(POL) ENV ENV ENV ENV POL
All this is remarkable and bears the mark of a desire for organization of a human nature:
LOGIC, SYMETRIES!!!!
This conclusion is summarized by Figure 49 below.
Figure 49: Is COVID-19 partially a “SYNTHETIC GENOME”?
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Figure 50: Evidence of 6 HIV/SIV cuntiguous inserts within a small COVID-19 region.
Ethical Considerations:
The 2 main results of this publication confront us with a paradox, in fact:
On the one hand, we have just demonstrated that this covid-19 genome contains an insertion of 6
strategic regions of HIV / SIV concentrated in a mini space representing less than 1% of the length
of the genome. One can think that such a "disturbance" can only have affected the global order of
the DNA of this genome.
On the other hand, we have also just shown that since the first SARS of 2003, the global order of
successive genomes was only increasing, highlighted here by stationary digital waves calibrated
on increasing Fibonacci numbers. In particular, covid-19 is structured over a long distance by a
21bp amplitude wave. However, the deletion in this genome of the small region including the 6
HIV / SIV inserts, will further gain in organization, causing waves of 34 bp to emerge (the number
of Fibonacci following 21 bp).
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We must conclude this remarkable fact:
To adapt to the disorder of its DNA resulting from the insertion of the 6 HIV / SIVs, the covid-19
genome has most certainly increased its level of global organization by adaptation mutations.
And we will now have to fear that this genome will continue to mutate in order to optimize its
overall level of organization ...
Acknowledgements
We especially thank Dr. Robert Friedman M.D. practiced nutritional and preventive medicine in
Santa Fe, New Mexico, woldwide expert on Golden ratio Life applications
(https://tinyurl.com/y9dxaauv). We also thank the mathematician Pr. Diego Lucio Rapoport
(Buenos aires), Marco F. Paya Torres (M.D Alicante), the french biologist Pr. François Gros
(Pasteur institute,co-discoverer of RNA messenger with James Watson and Walter Gilbert ),
Professor Sergey V. Petoukhov (Dr. Phys.-Math. Sci, Grand Ph.D., Full Professor, Laureate of the
State prize of the USSR), Volkmar Weiss (Dr. rer. nat. habil. Dr. phil. Habil. Leipzig, Germany),
and Pr. Luc Montagnier, medicine Nobel prizewinner for their interest in my research of
biomathematical laws of genomes. I especially thank Professor Luc Montagnier for his advice and
suggestions that led to this article.
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  • ... [15] we then searched in this genome for possible traces of HIV or even SIV. A first publication [5] reports the discovery of 6 HIV SIV RNA pieces relates to crucial retroviral genes like Enveloppe and RT Pol. The present article confirms and extends these initial results. ...
    ... Note: We will present below 12 + 4 HIV/SIV EIE in the sequential order of their addresses within COVID_19 genome. Initially, by focusing on the genome region mentioned in [4], we find and published [5] 6 first EIE located at the very beginning of this region. By a more in-depth exploration of this region (region "B" 330b), then exploring region "A" (of 600b) immediately located upstream of this region "B ", we discover, concentrated on less than 930b, 12 HIV SIV EIE. ...
    ... The origin of COVID-19 remains an open question : see particularly [14][15][16][17][18][19][20] and [5,27,30,33,34]. In this second part of DISCUSSION and RESULTS, we will present two types of facts: On the one hand, we will show that the 2 genomes of COVID_19 and Bat RaTG13 are exclusively distinguished from all the other genomes of SARS, MERS and other Bats. ...
    Research
    Full-text available
    We are facing the worldwide invasion of a new coronavirus. This follows several limited outbreaks of related viruses in various locations in a recent past (SARS, MERS). Although the main objective of researchers is to bring efficient therapeutic and preventive solutions to the global population, we need also to better understand the origin of the newly coronavirus-induced epidemic in order to avoid future outbreaks. The present molecular appraisal is to study by a bio-infomatic approach the facts relating to the virus and its precursors. This article shows how 16 fragments (Env Pol and Integrase genes) from different strains, both diversified and very recent, of the HIV1, HIV2 and SIV retroviruses have high percentage of homology into parts of the genome of COVID_19. Moreover each of these elements is made of 18 or more nucleotides and therefore may have function. They are called Exogenous Informative Elements (EIE).. Among these EIE, 12 are concentrated in a very small region of the COVID-19 genome, length less than 900bases, i.e. less than 3% of the total length of this genome. In addition, these EIE are positioned in 2 functional genes of COVID-19: the orf1ab and S spike genes. Here are the two main facts which contribute to our hypothesis of a partially synthetic genome: A contiguous region representing 2.49% of the whole COVID-19 genome of which 40.99% is made up of 12 diverse fragments originating from various strains of HIV SIV retroviruses. Some of these 12 EIE appear concatenated. Notably, the retroviral part of these regions, which consists of 8 elements from various strains HIV1, HIV2 and SIV covers a length of 275 contiguous bases of COVID-19. The cumulative length of these 8 HIV SIV elements represents 200 bases. Consequently, the HIV SIV density rate of this region of COVID-19 is 200/275 = 72.73%. A major part of these 16 EIE already existed in the first SARS genomes as early as 2003. However, we demonstrate how a new region including 4 HIV1 HIV2 Exogenous Informative Elements radically distinguishes all COVID-19 strains from all SARS and Bat strains with the exception of Bat RaTG13. We gather facts about the possible origins of COVID_19. We have particularly analyzed this small region of 225 bases common to COVID_19 and batRaTG13. We have studied the most recent genetic evolution of the COVID_19 strains involved in the world epidemic. We found a significant occurrence of mutations and deletions in the 225b area. On sampling genomes, we show that this 225b key region of each genome, rich in EIE, and the 1770bases SPIKE region evolve much faster than the corresponding whole genome (cases of 44 patients genomes from WA Seattle state, original epicenter in USA). In the comparative analysis of both SPIKES genes of COVID_19 and Bat RaTG13 we note two abnormal facts: 1-the insertion of 4 contiguous PRRA amino acids in the middle of SPIKE (we show that this site was already an optimal cleavage site BEFORE this insertion). 2-an abnormal distribution of synonymous codons in the second half of SPIKE. Finally we show the insertion in this 1770 bases SPIKE region of a significant EIE from Plasmodium Yoelii and of a possible HIV1 EIE with a crucial Spike mutation. INTRODUCTION :
  • ... [15] we then searched in this genome for possible traces of HIV or even SIV. A first publication [5] reports the discovery if 6 HIV SIV RNA pieces relates to crucial retroviral genes like Enveloppe and RT Pol. The present article confirms and extends these initial results. ...
    ... However, it is worth recalling here the history of successive discoveries from these regions. Initially, by focusing on the genome region mentioned in [4], we discovered and published [5] 6 first EIE located at the very beginning of this region. By a more in-depth exploration of this region (region "B" 330b), then exploring region "A" (of 600b) immediately located upstream of this region "B ", we discover, concentrated on less than 930b, 12 HIV SIV EIE. ...
    ... The origin of COVID-19 remains an open question : see particularly [14][15][16][17][18][19][20] and [5]. ...
    Preprint
    Full-text available
    We are facing the worldwide invasion of a new coronavirus. This follows several limited outbreaks of related viruses in various locations in a recent past (SARS, MERS). Although the main objective of researchers is to bring efficient therapeutic and preventive solutions to the global population, we need also to better understand the origin of the newly coronavirus-induced epidemic in order to avoid future outbreaks. The present molecular appraisal is to study by a bio-infomatic approach the facts relating to the virus and its precursors. This article shows how 16 fragments (Env Pol and Integrase genes) from different strains, both diversified and very recent, of the HIV1, HIV2 and SIV retroviruses most likely are present into the genome of COVID-19. Among these fragments, 12 are concentrated in a very small region of the COVID-19 genome, length less than 900bases, i.e. less than 3% of the total length of this genome. In addition, these footprints are positioned in 2 functional genes of COVID-19: the orf1ab and S spike genes. To sum up, here are the two main facts which contribute to our hypothesis of a partially synthetic genome: A contiguous region representing 2.49% of the whole COVID-19 genome of which 40.99% is made up of 12 diverse fragments originating from various strains of HIV SIV retroviruses. On the other hand, these 12 fragments some of which appear concatenated. Notably, the retroviral part of these regions, which consists of 8 elements from various strains HIV1, HIV2 and SIV covers a length of 275 contiguous bases of COVID-19. The cumulative length of these 8 HIV SIV elements represents 200 bases. Consequently, the HIV SIV density rate of this region of COVID-19 is 200/275 = 72.73%, which is considerable s made of. Moreover each of these elements is made of 18 or more nucleotides and therefore may have function. They are called Exogenous Informative Elements. A major part of these 16 EIE already existed in the first SARS genomes as early as 2003. However, we demonstrate how and why a new region including 4 HIV1 HIV2 Exogenous Informative Elements radically distinguishes all COVID-19 strains from all SARS and Bat strains. We then gather facts about the possible origins of COVID_19. We have particularly analyzed this small region of 225 bases common to COVID_19 and batRaTG13 but totally absent in all SARS strains. Then, we discuss the case of bat genomes presumed to be at the origin of COVID_19. In the strain of bat RaTG13 coronavirus isolated in 2013, then sequenced in 2020, the homology profile for HIV1 Kenya 2008 fragment is identical to that of COVID_19. Finally, we have studied the most recent genetic evolution of the COVID_19 strains involved in the world epidemic. We found a significant occurrence of mutations and deletions in the 225b region. On sampling genomes, we finally show that this 225b key region of each genome, rich in EIE, evolves much faster than the corresponding whole genome. The comparative analysis of the SPIKES genes of COVID_19 and Bat RaTG13 demonstrates two abnormal facts: on the one hand, the insertion of 4 contiguous amino acids in the middle of SPIKE, on the other hand, an abnormal distribution of synonymous codons in the second half of SPIKE. Finally the insertion in this region of an EIE coming from a Plasmodium Yoelii gene is demonstrated, but above all seems to explain the "strategy" pursued by having "artificially" modified the ratio of synonym codons / non-synonymous codons in this same region of 1770 COVID_19 SPIKE nucleotides. INTRODUCTION :
  • ... However, it is worth recalling here the history of successive discoveries from these regions. Initially, by focusing on the genome region mentioned in [4], we discovered and published [5] 6 first "EIE" located at the very beginning of this region. Then, by, on the one hand, a more in-depth exploration of this region (region "B" 330bp), then, on the other hand, by exploring region "A" (of 600bp) immediately located upstream of this region "B ", we discover, concentrated on less than 930bp, 12 HIV SIV "EIE". ...
    ... In the USA, the analysis of multiple sequences from the Seatle region (WA) and Minnesota shows a clear growing trees progressiveness in the mutations then successive deletions of the regions "A", "B" and 225 bases, thus : Table7 (ref 1 to 7, then 11 to 13), we progress from simple mutations to longer mutations on 3 codons, they affect HIV / SIV "EIE". Table9: also, there are grouped mutations (ref 4,5) affecting "EIE" areas. Table 10: here we illustrate at best a sort of "shedding" of "EIE" regions in which these genomes progress: thus, (ref 3 5 6 7), the mutations affect 2 or 3, then 8 consecutive bases. ...
    ... The question of the origin of COVID-19 remains an open question : see particularly [14][15][16][17][18][19][20] and [5]. To conclude, we will present first of all below some graphs and Tables of synthesis. ...
    Preprint
    Full-text available
    We human are facing the worldwide invasion of a new coronavirus. This follows several limited outbreaks of related viruses in various locations in a recent past (SARS, MERS). Although the main objective of researchers is to bring efficient therapeutic and preventive solutions to the global population, we need also to better understand the origin of the newly coronavirus-induced epidemic in order to avoid future new outbreaks. The present molecular appraisal is to study by a bio-infomatic approach the facts relating to the virus and its precursors. This article demonstrates how 16 « Exogeneous Informative Elements » fragments (Env Pol and Integrase genes) from different strains, both diversified and very recent, of the HIV1, HIV2 and SIV retroviruses most likely are present into the genome of COVID-19. Among these fingerprints, 12 of them would be concentrated in a very small region of the genome COVID-19 of length less than 900bases, i.e. less than 3% of the total length of this genome. In addition, these footprints are positioned in 2 functional genes of COVID-19: the orf1ab and S spike genes.To sum up, here are the two main facts which contribute to our hypothesis of a partially synthetic genome: A contiguous region representing 2.49% of the whole COVID-19 genome is 40.99% made up of 12 diverse Exogeneous Informative Elements (EIE) fragments originating from various strains of HIV SIV retroviruses. On the other hand, these 12 Exogeneous Informative Elements, some of them appear concatenated, that is to say placed side by side in the genome of COVID-19, and this despite natures, strains, and years of emergence all different. Notably, the retroviral part of these regions, which consists of 8 motifs from various strains HIV1, HIV2 and SIV, covers a length of 275 contiguous bases of COVID-19. The cumulative length of these 8 HIV SIV motifs represents 200 bases. Consequently, the HIV SIV density rate of this region of COVID-19 is 200/275 = 72.73%, which is considerable.A major part of these 16 EIE Elements already existed in the first SARS genomes as early as 2003. However, we demonstrate how and why a new region including 4 HIV1 HIV2 Exogeneous Informative Elements radically distinguishes all COVID-19 strains from all SARS and Bat strains. Particularly, we will be interested in the Bat RaTG13 strain whose genomic proximity to COVID-19 will be thoroughly analyzed. Then, we gather facts about the possible origins of COVID_19, we have particularly analyze this small region of 225 bases common to COVID_19 and batRaTG13 but totally absent in all SARS strains. Then, we discuss the case of bat genomes presumed to be at the origin of COVID_19. In the strain of bat RaTG13 bat coronavirus isolated in 2013, then sequenced in 2020, the homology profile for HIV1 Kenya 2008 fingerprint is identical to that of COVID_19. (collected end december 2019, then sequenced in 2020). Finally, we have studied the most recent genetic evolution of the COVID_19 strains involved in the world epidemic. We found an astoneshing occurrence of mutations and deletions in the 225b region.On sampling genomes, we finally show that this 225b key region of each genome, rich in "EIE", evolves much faster than the corresponding whole genome.
  • Article
    Background: In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods: We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings: The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation: 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding: National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
  • Preprint
    Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.
  • Article
    The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission. Research Highlights • Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.
  • Article
    CRISPR-Cas nucleases are powerful tools for manipulating nucleic acids; however, targeted insertion of DNA remains a challenge, as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase from cyanobacteria Scytonema hofmanni (ShCAST) that consists of Tn7-like transposase subunits and the type V-K CRISPR effector (Cas12k). ShCAST catalyzes RNA-guided DNA transposition by unidirectionally inserting segments of DNA 60 to 66 base pairs downstream of the protospacer. ShCAST integrates DNA into targeted sites in the Escherichia coli genome with frequencies of up to 80% without positive selection. This work expands our understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion.
  • Article
    Understanding how to program biological functions into artificial DNA sequences remains a key challenge in synthetic genomics. Here, we report the chemical synthesis and testing of Caulobacter ethensis-2.0 ( C. eth-2.0 ), a rewritten bacterial genome composed of the most fundamental functions of a bacterial cell. We rebuilt the essential genome of Caulobacter crescentus through the process of chemical synthesis rewriting and studied the genetic information content at the level of its essential genes. Within the 785,701-bp genome, we used sequence rewriting to reduce the number of encoded genetic features from 6,290 to 799. Overall, we introduced 133,313 base substitutions, resulting in the rewriting of 123,562 codons. We tested the biological functionality of the genome design in C. crescentus by transposon mutagenesis. Our analysis revealed that 432 essential genes of C. eth-2.0 , corresponding to 81.5% of the design, are equal in functionality to natural genes. These findings suggest that neither changing mRNA structure nor changing the codon context have significant influence on biological functionality of synthetic genomes. Discovery of 98 genes that lost their function identified essential genes with incorrect annotation, including a limited set of 27 genes where we uncovered noncoding control features embedded within protein-coding sequences. In sum, our results highlight the promise of chemical synthesis rewriting to decode fundamental genome functions and its utility toward the design of improved organisms for industrial purposes and health benefits.
  • Article
    A redesigned yeast genome is being constructed to allow it to be extensively rearranged on demand. A suite of studies reveals the versatility of the genome-shuffling system, and shows how it could be used for biotechnology applications.