Don2 (Don1 Revised)
Contributor
barbos and others,
I cannot read the full article. It seems to start talking about codon usage preference, which is something I had mentioned in post#1601. Here is my post:
Before discussing, let me say that lately my views have changed somewhat, I agree that two things are suspicious: the location of Wuhan and the spike protein. However, what I am not saying is that I think it's likely a lab leak. I'm not saying that. Things are often continua in life and to me this is one of those things...where we look at this and think in terms of probabilities and unknowns.
Okay, now, having said that, a few things...
At some level, there are some similarities to Intelligent Design arguments and fallacies. At some level there also are not, but I think one should strive not to make those types of arguments or fall into those kinds of traps. So, at this high level, you're arguing, the virus was manufactured (intelligently designed) and someone else is saying, no, it naturally evolved. Then, you're saying, "but look at this little thing here...it's so odd...how could nature have naturally evolved that?"
I'm saying outright, I am over-simplifying the arguments because I don't want the arguments to engage in confirmation bias, cherry-picking, a theory of gaps or any other nonsense. Let me repeat two objections I have posted in the thread.
(1) In post#1562, I linked to a scientific paper that says that furin cleavage sites naturally occur in nature. I even gave a graphic from their published paper:
View attachment 33896
(2) In post#1601, I am questioning specifically the argument of codon usage bias/preference. I've made a specific point. It's there are relationships between a virus' codon usage and its host's codon usage. Let's call virus codon usage V and let's call host codon usage H. Then, sort of--kind of-- V = f(H). But then the virus jumps host. So there is a new H, let's call it H2. You are saying, "Look, V != f(H) at a single point of change of some 12nt without examining the other 1000nt!!!11" But I am saying "Maybe that's because when viruses swap hosts, you should be thinking in terms of V=f(H2)."
It also appears to be more complicated than that...not only is there some statistical distribution of codons it may use under one host, but also whether the particular synonymous codon sequence is used or not may depend upon the function of the particular gene in the host. Sometimes, it is efficient for the virus to have similar codon usage to the host and sometimes it is efficient for the virus to have dissimilar codon usage to the host depending upon the function of the gene. It isn't quite well understood either over the expanse of all functions, all the ones which would be either one or neither. In any case, let F=function of the gene. Then, V=f(H2,F); not V=f(H).
I think it's standard practice to assume the opposite conclusion you want. In this case if you want to show the lab leak hypothesis is well-founded, then you'd want to start with assuming Nature. Next, you want to say, BUT if Nature, then why?! That's your next step. Here, though, you aren't assuming nature the way nature works. Because allegedly under the natural hypothesis, there is some intermediate host or human host, not sure which...where this change would have occurred. So you'd want to consider V=f(H2,F)...but you also wouldn't be cherry-picking just this site in order to make a statistical argument. And you kind of would want to know the intermediate host in order to know if CGG would be rare or not in a coronavirus that infects that host but like I wrote you want to look at the whole change and provide statistics.
Here are some papers on this topic that could be of interest:
Dissimilation of synonymous codon usage bias in virus–host coevolution due to translational selection
Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation
Evolution of Codon Usage Bias in Henipaviruses Is Governed by Natural Selection and Is Host-Specific
However, perhaps there is something still there. Perhaps if someone were to understand furin and look at codon usage bias cleavage sites in viruses with human hosts [or intermediate hosts], we could see if CGG is rare or not, but especially one could construct the ancestor of cov2 virus, examine the changes and check if their codon usage bias in the changes make sense after the jump to intermediate host/human, rather than cherry-picking a specific site where something seems weird and saying "Ahah!" And that doesn't mean to cherry-pick a couple other sites within a > 1000nt change to say those look suspicious, too, but instead to examine the full difference and look at statistics.
Still Suspicious
All the scientific objections above said, it still appears to be plausible that the Wuhan outbreak was related to the Wuhan virus research in some way so that from a package received, sample obtained, or virus manipulated at the WIV lab, another lab or institution, a "leak" could have happened. What makes it a little more suspicious is that the infectiousness seems to have happened very recently and since Wuhan was the first known highly infectious outbreak, one would think the jump to human happened there or near there. When you couple that with the gain of function research which is essentially jump-to-human research, it does look suspicious. I believe China is looking for the source to the outbreak, if it were natural, and so over time as China does not identify the source, I am also becoming more suspicious that the source could have been Wuhan.
I cannot read the full article. It seems to start talking about codon usage preference, which is something I had mentioned in post#1601. Here is my post:
Before discussing, let me say that lately my views have changed somewhat, I agree that two things are suspicious: the location of Wuhan and the spike protein. However, what I am not saying is that I think it's likely a lab leak. I'm not saying that. Things are often continua in life and to me this is one of those things...where we look at this and think in terms of probabilities and unknowns.
Okay, now, having said that, a few things...
At some level, there are some similarities to Intelligent Design arguments and fallacies. At some level there also are not, but I think one should strive not to make those types of arguments or fall into those kinds of traps. So, at this high level, you're arguing, the virus was manufactured (intelligently designed) and someone else is saying, no, it naturally evolved. Then, you're saying, "but look at this little thing here...it's so odd...how could nature have naturally evolved that?"
I'm saying outright, I am over-simplifying the arguments because I don't want the arguments to engage in confirmation bias, cherry-picking, a theory of gaps or any other nonsense. Let me repeat two objections I have posted in the thread.
(1) In post#1562, I linked to a scientific paper that says that furin cleavage sites naturally occur in nature. I even gave a graphic from their published paper:
View attachment 33896
(2) In post#1601, I am questioning specifically the argument of codon usage bias/preference. I've made a specific point. It's there are relationships between a virus' codon usage and its host's codon usage. Let's call virus codon usage V and let's call host codon usage H. Then, sort of--kind of-- V = f(H). But then the virus jumps host. So there is a new H, let's call it H2. You are saying, "Look, V != f(H) at a single point of change of some 12nt without examining the other 1000nt!!!11" But I am saying "Maybe that's because when viruses swap hosts, you should be thinking in terms of V=f(H2)."
It also appears to be more complicated than that...not only is there some statistical distribution of codons it may use under one host, but also whether the particular synonymous codon sequence is used or not may depend upon the function of the particular gene in the host. Sometimes, it is efficient for the virus to have similar codon usage to the host and sometimes it is efficient for the virus to have dissimilar codon usage to the host depending upon the function of the gene. It isn't quite well understood either over the expanse of all functions, all the ones which would be either one or neither. In any case, let F=function of the gene. Then, V=f(H2,F); not V=f(H).
I think it's standard practice to assume the opposite conclusion you want. In this case if you want to show the lab leak hypothesis is well-founded, then you'd want to start with assuming Nature. Next, you want to say, BUT if Nature, then why?! That's your next step. Here, though, you aren't assuming nature the way nature works. Because allegedly under the natural hypothesis, there is some intermediate host or human host, not sure which...where this change would have occurred. So you'd want to consider V=f(H2,F)...but you also wouldn't be cherry-picking just this site in order to make a statistical argument. And you kind of would want to know the intermediate host in order to know if CGG would be rare or not in a coronavirus that infects that host but like I wrote you want to look at the whole change and provide statistics.
Here are some papers on this topic that could be of interest:
Dissimilation of synonymous codon usage bias in virus–host coevolution due to translational selection
Codon usage similarity between viral and some host genes suggests a codon-specific translational regulation
Evolution of Codon Usage Bias in Henipaviruses Is Governed by Natural Selection and Is Host-Specific
However, perhaps there is something still there. Perhaps if someone were to understand furin and look at codon usage bias cleavage sites in viruses with human hosts [or intermediate hosts], we could see if CGG is rare or not, but especially one could construct the ancestor of cov2 virus, examine the changes and check if their codon usage bias in the changes make sense after the jump to intermediate host/human, rather than cherry-picking a specific site where something seems weird and saying "Ahah!" And that doesn't mean to cherry-pick a couple other sites within a > 1000nt change to say those look suspicious, too, but instead to examine the full difference and look at statistics.
Still Suspicious
All the scientific objections above said, it still appears to be plausible that the Wuhan outbreak was related to the Wuhan virus research in some way so that from a package received, sample obtained, or virus manipulated at the WIV lab, another lab or institution, a "leak" could have happened. What makes it a little more suspicious is that the infectiousness seems to have happened very recently and since Wuhan was the first known highly infectious outbreak, one would think the jump to human happened there or near there. When you couple that with the gain of function research which is essentially jump-to-human research, it does look suspicious. I believe China is looking for the source to the outbreak, if it were natural, and so over time as China does not identify the source, I am also becoming more suspicious that the source could have been Wuhan.
