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Natural genetic resistence to Covid-19

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  • #76
    Originally posted by TheLurch View Post
    My goodness, finally, something that looks like evidence. Will read within the next few days.
    All the references together present aspects of the evidence and the professional view of the natural evolved genetic and possible cultural response resistance to COVID-19. Also the references poit to the fact that this is the same pattern for many viruses.

    One brute fact is the rate of infection, hospitalization, and fatalities are lowest in humans by a very large degree in the region of origin Southeast Asia and very South China of the related covid viruses are present in the animal populations related to the one that caused COVID-19, and in the Asia regions surrounding Southeast Asia are lower than the rest of the world. The pattern is very consistent with the known regional patterns of epidemics and pandemics in the relationship between humans and viruses.

    Though there is a degree of uncertainty at present to the degree of natural evolved development of genetic and cultural resistance in human populations. I do not believe there is an adequate alternate explanation that accounts for the pattern of the extreme differences of regional impact of COVID-19 in the different regions of the world..
    Last edited by shunyadragon; 02-03-2022, 09:39 AM.
    Glendower: I can call spirits from the vasty deep.
    Hotspur: Why, so can I, or so can any man;
    But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

    go with the flow the river knows . . .

    Frank

    I do not know, therefore everything is in pencil.

    Comment


    • #77
      The following article provides more details of contemporary research concerning the history of viruses and their related to the history of the relationship to humans. The evolutionary tree and related research presented here provides more details as to the relationship of the viruses over time and human history. I believe the research demonstrates that the viruses related to SARS COVID-1 and SARS COVID-2 originated in the Southeast China and South China, and in particular one province. The spread of related viruses across Asia to Europe and Africa occurred through human migration and trade in the hundreds to thousands ot years. One closely related virus in Africa is likely from extensive trade between Africa and China up to the Tang Dynasty.

      This research deals mainly with the gene related to ACE2 binding in coronaviruses, which is the principle transmission of the virus from animal hosts to humans. This research does not deal with the other genetic factors of the coronaviruses that influence the transmission, severity and fatality of the related coronaviruses.

      A previous reference demonstrated evidence of a related COVID epidemic ~20,000 years ago in South China/Southeast Asia.

      Source: https://www.fredhutch.org/en/news/center-news/2022/02/starr-bloom-ace2-binding-evolution.html



      Coronavirus’ distant past reveals ancient roots of trait that could help them jump species

      SARS-related coronaviruses with theoretical spillover potential more widespread than previously thought.

      FEBRUARY 3, 2022 • BY SABRINA RICHARDS / FRED HUTCH NEWS S study of the distant evolution of SARS-related coronavirus spike proteins (red) shows that more may be able to bind ACE2 receptors than previously thought.

      To infect our cells, SARS-CoV-2’s spike protein turns the key on the molecular doorway formed by our ACE2 protein. Mutations that adapted its spike protein to human ACE2 helped the virus make its way out of bats, where SARS-related coronaviruses have circulated for thousands of years, and eventually trigger the COVID-19 pandemic. After the smaller SARS epidemic in the early 2000s, COVID-19 is the second viral outbreak driven by a coronavirus that acquired the key to our cells.

      New work, published Thursday in the journal Nature from scientists at Fred Hutchinson Cancer Research Center and the University of Washington, suggests that to safeguard against other coronaviruses that could gain the ability to sneak into our cells, we need to think globally. The researchers found that the ability to bind ACE2 — a crucial trait in species-jumping coronaviruses — could be a more widespread possibility than previously thought. Instead of being a late evolutionary development, the ability to bind ACE2 is an ancient property of bat SARS-related coronaviruses — and found in coronaviruses outside of Asia.

      The researchers found that many of the coronaviruses that already bind one species’ ACE2 can jump to another species’ ACE2 (including humans’) by switching a single protein building block, or amino acid. Binding to human ACE2 is not the only requirement for spillover into humans, but it’s an important hurdle a coronavirus must clear to start a pandemic, said Dr. Tyler Starr, the postdoctoral fellow in Hutch evolutionary biologist Dr. Jesse Bloom’s lab who led the work.

      Researchers who are working on broad coronavirus vaccines and treatments in preparation for future viral spillovers must take these more distantly related viruses into account, he said.

      “People who are working on surveillance and therapeutic antibody development need to expand their breadth,” Starr said. “If you don’t test viruses [from around the world] you’re missing the plot. We don’t know where the next pandemic might come from.”

      The findings also highlight the care that should be taken in handling and sampling coronaviruses with unknown ACE2 binding potential, he said.
      A phylogenetic tree of SARS-related coronavirus spike protein receptor-binding domains showing the main family groups, or clades. Blue viruses are most closely related to SARS-CoV-2, the source of the COVID-19 pandemic. Green viruses are most closely related to SARS-CoV-1, which triggered the SARS epidemic in 2002. The yellow viruses form another clade in Asia, while viruses in the pink clade circulate in Europe and Africa.Starr, Zepeda et. al, Nature 2021An evolutionary tree doesn’t add up


      Starr, who joined Bloom’s lab to study HIV and quickly pivoted to SARS-CoV-2 when the COVID-19 pandemic struck, was inspired to study the origins of ACE2 binding in SARS-related coronaviruses (known as sarbecoviruses) after researching the hunt for the origins of SARS-CoV-1, which caused an epidemic in Asia in 2003.

      “It was a 10-year process, and there was a debate the whole time,” he said.

      Although many bat viruses with genetic similarity to SARS-CoV-1 were found across China during this time, they were genetically distinct, and none of these viruses were found to use ACE2 proteins as their entry receptor.

      It wasn’t until 2013 that researchers announced they’d found a related bat coronavirus whose key fit the lock of the human ACE2, marking these bat viruses as a proximal source of the SARS-CoV-1 epidemic. Scientists worried about future spillovers intensified their searches for more ACE2-binding bat coronaviruses, which continued to be found in just a single province in Southern China, even though sarbecoviruses are found throughout the world.

      Many bat sarbecoviruses in Asia, Europe, and Africa did not appear to use ACE2 as their entry point, leading researchers to conclude that it was a trait that had appeared late in coronavirus evolution.

      But when Starr studied the tree of sarbecovirus evolution, he wasn’t convinced.

      “SARS-CoV-2 sprung from a branch where we weren’t looking [for a new spillover event],” Starr said.

      He suspected that the hyper-focus on ACE2-binding bat coronaviruses in one region of the world had blinded scientists to the origins of ACE2 binding in coronaviruses.

      “It seemed like there was potential that using ACE2 is a trait writ large,” he said. “Using ACE2 in general could be a more widespread trait than was previously appreciated.”

      What if the coronaviruses that didn’t use ACE2 to infect were the exception, instead of the rule?

      ACE2 binding is an ancient characteristic

      The region of the coronavirus spike protein that interacts with ACE2 is called the receptor-binding domain, or RBD. To assess whether ACE2 binding is a new or old characteristic, Starr amassed 45 RBD genes from across the four known, closely related subgroups of RBDs across the SARS-related coronavirus family. These subgroups, also known as clades, describe related RBDs that can be traced to the same branch point off the sarbecovirus evolutionary tree. SARS-Cov-2 and SARS-CoV-1 RBDs fall into different clades with closely related bat viru ses, both in Asia. Starr’s survey included two RBDs from a clade of sarbecoviruses circulating in bats in Europe and Africa, which diverged from Asian sarbecoviruses hundreds or thousands of years ago.

      © Copyright Original Source



      Read further . . .
      Last edited by shunyadragon; 02-07-2022, 11:54 AM.
      Glendower: I can call spirits from the vasty deep.
      Hotspur: Why, so can I, or so can any man;
      But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

      go with the flow the river knows . . .

      Frank

      I do not know, therefore everything is in pencil.

      Comment


      • #78
        Originally posted by shunyadragon View Post
        All the references together present aspects of the evidence and the professional view of the natural evolved genetic and possible cultural response resistance to COVID-19. Also the references poit to the fact that this is the same pattern for many viruses.
        So, I've had a chance to read the paper. It's definitely much closer to evidence that would support your argument, but it's not quite.

        The researchers involved started with a list of genes that have been found to interact with coronaviruses, and looked for evidence of what are called "selective sweeps". These are cases where.a genetic variant faces strong positive selection, so sweeps through a population until it's present at very high levels. When it does this, it tends to take along all the nearby DNA on the chromosome, since there's limited time for it to recombine away nearby sequences. You can make an estimate of how long ago the sweep took place based on how long the original surrounding sequences are.

        So, the researchers find evidence that a selective sweep took place starting about 25,000 years ago, in a single population that was ancestral to four modern day East Asian populations. Given that the genes were associated with coronavirus, the researchers suggest that a severe and extended epidemic took place to drive evolution of protection. Whatever caused it, the selection stopped about 5,000 to 10,000 years ago.

        So, it's in keeping with the idea of regional selection in the past, since these variants don't seem to have swept through elsewhere. But it's a single event, and the genes haven't been under selection for some time, so it's not clear whether it's after effects are still significant.

        It's solid work. One big caveat is that a lot of proteins stick to each other spuriously, so at least some of the ones examined here are going to be irrelevant. And there's no way of telling whether the virus spread to other populations and drove selection for different genes in them.

        Meanwhile... I decided to take a look at the basic premise here.
        Originally posted by shunyadragon View Post
        Though there is a degree of uncertainty at present to the degree of natural evolved development of genetic and cultural resistance in human populations. I do not believe there is an adequate alternate explanation that accounts for the pattern of the extreme differences of regional impact of COVID-19 in the different regions of the world..
        Is there really a regional difference in the biology? Or is it potentially an issue either with reporting, or due to differences in public health?

        To handle the reporting issue, you can look at the excess mortality compared to what would be expected simply by scaling previous trends to account for population growth. I've done that using Our World in Data for a few countries, adjusted per capita..
        Screen Shot 2022-02-07 at 10.44.56 PM.png

        As you can see, there are some Asian countries with levels of excess mortality similar to those of European countries. And some European countries have levels of excess death well below that of Asian countries. So, I think the premise of dramatic regional differences based on genetics seems suspect; it seems more likely to be a matter national differences based on a combination of public health policy and testing capacity.
        "Any sufficiently advanced stupidity is indistinguishable from trolling."

        Comment


        • #79
          Originally posted by TheLurch View Post
          So, I've had a chance to read the paper. It's definitely much closer to evidence that would support your argument, but it's not quite.

          The researchers involved started with a list of genes that have been found to interact with coronaviruses, and looked for evidence of what are called "selective sweeps". These are cases where.a genetic variant faces strong positive selection, so sweeps through a population until it's present at very high levels. When it does this, it tends to take along all the nearby DNA on the chromosome, since there's limited time for it to recombine away nearby sequences. You can make an estimate of how long ago the sweep took place based on how long the original surrounding sequences are.

          So, the researchers find evidence that a selective sweep took place starting about 25,000 years ago, in a single population that was ancestral to four modern day East Asian populations. Given that the genes were associated with coronavirus, the researchers suggest that a severe and extended epidemic took place to drive evolution of protection. Whatever caused it, the selection stopped about 5,000 to 10,000 years ago.

          So, it's in keeping with the idea of regional selection in the past, since these variants don't seem to have swept through elsewhere. But it's a single event, and the genes haven't been under selection for some time, so it's not clear whether it's after effects are still significant.

          It's solid work. One big caveat is that a lot of proteins stick to each other spuriously, so at least some of the ones examined here are going to be irrelevant. And there's no way of telling whether the virus spread to other populations and drove selection for different genes in them.

          Meanwhile... I decided to take a look at the basic premise here.

          Is there really a regional difference in the biology? Or is it potentially an issue either with reporting, or due to differences in public health?

          To handle the reporting issue, you can look at the excess mortality compared to what would be expected simply by scaling previous trends to account for population growth. I've done that using Our World in Data for a few countries, adjusted per capita..
          Screen Shot 2022-02-07 at 10.44.56 PM.png

          As you can see, there are some Asian countries with levels of excess mortality similar to those of European countries. And some European countries have levels of excess death well below that of Asian countries. So, I think the premise of dramatic regional differences based on genetics seems suspect; it seems more likely to be a matter national differences based on a combination of public health policy and testing capacity.
          Your reference was not legible as posted. I will have to look closer

          'Some countries' is a suspect response. I referred to in the specific region of origin in Southeast China and South China as referenced as centered one province where the bats carrying the closest related coronavirus lived in caves, and residents around this region carry antibodies of previous exposure to related coronaviruses. As you move away from this region fatalities/million does increase. In some countries and regions like Canada, Greenland and Africa have low fatalities/million, in part due to low population differences and relatively low travel among populations. I will have to look closer at data, because I would refer to deaths/million.

          The research demonstrates that the region of historical origin of related Coronaviruses is the specific region of Southeast Asia and very South China, and spread to the rest of the world in the past hundreds or thousands of years by human migration and trade. The very closely related virus found in Africa like got there through trade with China that ended in the Tang Dynasty.
          Last edited by shunyadragon; 02-08-2022, 07:25 AM.
          Glendower: I can call spirits from the vasty deep.
          Hotspur: Why, so can I, or so can any man;
          But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

          go with the flow the river knows . . .

          Frank

          I do not know, therefore everything is in pencil.

          Comment


          • #80
            Originally posted by shunyadragon View Post

            Your reference was not legible as posted. I will have to look closer

            'Some countries' is a suspect response. I referred to in the specific region of origin in Southeast China and South China as referenced as centered one province where the bats carrying the closest related coronavirus lived in caves, and residents around this region carry antibodies of previous exposure to related coronaviruses.
            If you want to limit yourself to south China, then the paper I was discussing in my previous post - the one you had earlier brought in as evidence for your contention - is irrelevant. It applies broadly to most East Asian populations, and so is not evidence for selection in a narrow subregion of East Asia.

            Originally posted by shunyadragon View Post
            The research demonstrates that the region of historical origin of related Coronaviruses is the specific region of Southeast Asia and very South China, and spread to the rest of the world in the past hundreds or thousands of years by human migration and trade. The very closely related virus found in Africa like got there through trade with China that ended in the Tang Dynasty.
            I have no idea what you mean by "historical origin of related Coronaviruses". All coronaviruses are related, and we don't know where their ancestors originated.
            "Any sufficiently advanced stupidity is indistinguishable from trolling."

            Comment


            • #81
              Originally posted by TheLurch View Post
              If you want to limit yourself to south China, then the paper I was discussing in my previous post - the one you had earlier brought in as evidence for your contention - is irrelevant. It applies broadly to most East Asian populations, and so is not evidence for selection in a narrow subregion of East Asia.
              Iis not a narrow subregion as you present. The deaths/million are lower in the countries referenced in your reference if you do not want recognize any sort of subregion.

              I have no idea what you mean by "historical origin of related Coronaviruses". All coronaviruses are related, and we don't know where their ancestors originated.
              As per reference provided

              Glendower: I can call spirits from the vasty deep.
              Hotspur: Why, so can I, or so can any man;
              But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

              go with the flow the river knows . . .

              Frank

              I do not know, therefore everything is in pencil.

              Comment


              • #82
                Originally posted by shunyadragon View Post

                Iis not a narrow subregion as you present. The deaths/million are lower in the countries referenced in your reference if you do not want recognize any sort of subregion.
                You've seemed to use China, South China, East Asia, and Asia interchangeably. I am asking you to clarify your argument: what do you consider the region at issue.

                Originally posted by shunyadragon View Post
                As per reference provided
                I'm asking you to explain your own references, because I can't figure out how to map what they say onto what you say about them. Surely, explaining your own argument shouldn't be a problem, right?
                "Any sufficiently advanced stupidity is indistinguishable from trolling."

                Comment


                • #83
                  Originally posted by TheLurch View Post
                  You've seemed to use China, South China, East Asia, and Asia interchangeably. I am asking you to clarify your argument: what do you consider the region at issue.
                  No I am refrreing to the region that involves thes countries collectively. It is a regional issue and not national borders.


                  I'm asking you to explain your own references, because I can't figure out how to map what they say onto what you say about them. Surely, explaining your own argument shouldn't be a problem, right?
                  Read the references.

                  Glendower: I can call spirits from the vasty deep.
                  Hotspur: Why, so can I, or so can any man;
                  But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                  go with the flow the river knows . . .

                  Frank

                  I do not know, therefore everything is in pencil.

                  Comment


                  • #84
                    Originally posted by shunyadragon View Post

                    No I am refrreing to the region that involves thes countries collectively. It is a regional issue and not national borders.
                    But what region are you referring to? Describe it.

                    Originally posted by shunyadragon View Post
                    Read the references.
                    I have. I'm trying to understand the parameters of the argument you're making based on the references.
                    "Any sufficiently advanced stupidity is indistinguishable from trolling."

                    Comment


                    • #85
                      Originally posted by TheLurch View Post
                      But what region are you referring to? Describe it.
                      I already did, and the references discussed and described the origin and evolution of related coronaviruses..


                      I have. I'm trying to understand the parameters of the argument you're making based on the references.
                      . . . because you have not read the references. For beginning reread the reference in post #73. The reference in post #77 described the recent evolution and migration of the related coronaviruses in Africa and Asia as originating from the Southeast Asia region referenced.
                      Last edited by shunyadragon; 02-10-2022, 07:52 AM.
                      Glendower: I can call spirits from the vasty deep.
                      Hotspur: Why, so can I, or so can any man;
                      But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                      go with the flow the river knows . . .

                      Frank

                      I do not know, therefore everything is in pencil.

                      Comment


                      • #86
                        Originally posted by shunyadragon View Post
                        . . . because you have not read the references. For beginning reread the reference in post #73. The reference in post #77 described the recent evolution and migration of the related coronaviruses in Africa and Asia as originating from the Southeast Asia region referenced.
                        This is the problem. I read it, and it does not say anything like that.

                        It indicates that the ancestral form of the spike protein, found in viruses in Africa and Europe, binds to a specific protein on cells. It indicates that the viruses in SE Asia are an offshoot of this lineage where some viruses have spike proteins with an affinity for a different protein. In other words, the SE Asian viruses are derived from global population, not ancestral to it:

                        “This suggests that in Africa and Europe, viruses are probably also using ACE2, and it's this one clade in Southeast Asia that lost ACE2 binding that's so heavily sampled that is actually the outlier,” Starr said.
                        This is why you can't just say "read the references" - you're often wrong about what the references say, which makes it impossible to understand what you're trying to say. In the future, please quote the specific part of the reference that you're interpreting.
                        "Any sufficiently advanced stupidity is indistinguishable from trolling."

                        Comment


                        • #87
                          Originally posted by TheLurch View Post
                          This is the problem. I read it, and it does not say anything like that.

                          It indicates that the ancestral form of the spike protein, found in viruses in Africa and Europe, binds to a specific protein on cells. It indicates that the viruses in SE Asia are an offshoot of this lineage where some viruses have spike proteins with an affinity for a different protein. In other words, the SE Asian viruses are derived from global population, not ancestral to it:



                          This is why you can't just say "read the references" - you're often wrong about what the references say, which makes it impossible to understand what you're trying to say. In the future, please quote the specific part of the reference that you're interpreting.
                          I do not believe tis is accurate. The article I believe the origin indicates the origin is ancestral from the Asia viruses hundreds or thousands of years ago.

                          Previous source . . .

                          ACE2 binding is an ancient characteristic

                          The region of the coronavirus spike protein that interacts with ACE2 is called the receptor-binding domain, or RBD. To assess whether ACE2 binding is a new or old characteristic, Starr amassed 45 RBD genes from across the four known, closely related subgroups of RBDs across the SARS-related coronavirus family. These subgroups, also known as clades, describe related RBDs that can be traced to the same branch point off the sarbecovirus evolutionary tree. SARS-Cov-2 and SARS-CoV-1 RBDs fall into different clades with closely related bat viruses, both in Asia. Starr’s survey included two RBDs from a clade of sarbecoviruses circulating in bats in Europe and Africa, which diverged from Asian sarbecoviruses hundreds or thousands of years ago.
                          Glendower: I can call spirits from the vasty deep.
                          Hotspur: Why, so can I, or so can any man;
                          But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                          go with the flow the river knows . . .

                          Frank

                          I do not know, therefore everything is in pencil.

                          Comment


                          • #88
                            Interesting Article from National Geographic the nature and natural rates of mutation history of coronaviruses, compared to other viruses and how they jump from animals to humans and among the human population. The role of immune compromised individuals and in the nutation rates to resistant strains is discussed.

                            This is a layman's summery and not the specific scientific journal article.

                            Source: https://www.nationalgeographic.com/science/article/the-3-main-theories-for-omicrons-origins




                            The 3 main theories for Omicron's origins


                            Scientists are trying to pinpoint where and how the highly transmissible variant emerged so they can be better prepared for the next one.
                            BYPRIYANKA RUNWAL
                            PUBLISHED FEBRUARY 15, 2022
                            • 9 MIN READOmicron’s arrival in November 2021 took scientists by surprise. Not because there was a new variant on the block, but because it had many and unusual mutations—some rare and others that had never been seen before. Also, its closest relatives weren’t recent variants but earlier versions of SARS-CoV-2, the virus that causes COVID-19, circulating more than a year ago.

                            That left the scientific community wondering where, exactly, Omicron came from. Some research suggests that this variant may have evolved in the body of someone who was immunocompromised; other molecular clues suggest that the virus jumped from a human to an animal where it evolved before jumping back into a human host.

                            It’s normal for a virus to mutate as it spreads from person to person, inevitably producing errors in its genetic code as it multiples. While most mutations may be benign, if any give the virus a survival advantage by making it, say, more transmissible or by aiding its ability to escape the host’s immune system, it may persist and result in new variants with more worrying traits.

                            “I don’t think other variants of concern are that much of a surprise compared to Omicron, which kind of came out of nowhere,” says Angela Rasmussen, a virologist at the University of Saskatchewan in Canada.

                            Analysis of its genome suggests that Omicron likely diverged from the original SARS-CoV-2 lineage in mid-2020. The SARS-CoV-2 virus typically acquires two mutations per month. For every lineage that’s been in circulation, “that [rate of mutation] has been pretty constant,” says Francois Balloux, a computational biologist at the University College London Genetics Institute in the United Kingdom. Over the course of about 18 months, that rate of mutation would suggest that the divergent virus strain would have acquired roughly 36 mutations.

                            But sequencing the Omicron’s genetic code revealed more than 50 mutations, of which at least 30 are in its critically important spike protein, which is essential for infecting human cells. “That’s a big jump,” Balloux says. Also, many of these mutations are clustered around the region in the spike where antibodies bind, blocking the ability of SARS-CoV-2 to enter the cell.

                            © Copyright Original Source



                            Read the full article for complete understanding.


                            Glendower: I can call spirits from the vasty deep.
                            Hotspur: Why, so can I, or so can any man;
                            But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                            go with the flow the river knows . . .

                            Frank

                            I do not know, therefore everything is in pencil.

                            Comment


                            • #89
                              Originally posted by shunyadragon View Post

                              I do not believe tis is accurate. The article I believe the origin indicates the origin is ancestral from the Asia viruses hundreds or thousands of years ago.

                              Previous source . . .

                              ACE2 binding is an ancient characteristic

                              The region of the coronavirus spike protein that interacts with ACE2 is called the receptor-binding domain, or RBD. To assess whether ACE2 binding is a new or old characteristic, Starr amassed 45 RBD genes from across the four known, closely related subgroups of RBDs across the SARS-related coronavirus family. These subgroups, also known as clades, describe related RBDs that can be traced to the same branch point off the sarbecovirus evolutionary tree. SARS-Cov-2 and SARS-CoV-1 RBDs fall into different clades with closely related bat viruses, both in Asia. Starr’s survey included two RBDs from a clade of sarbecoviruses circulating in bats in Europe and Africa, which diverged from Asian sarbecoviruses hundreds or thousands of years ago.
                              That doesn't indicate what you seem to think it does. The ancestral population appears to be ACE2 binding, and has a global distribution. Some small clades in a specific region do not have ACE-2 binding. The most parsimonious explanation is that the small clades are derived from the global population.
                              "Any sufficiently advanced stupidity is indistinguishable from trolling."

                              Comment


                              • #90
                                Originally posted by TheLurch View Post
                                That doesn't indicate what you seem to think it does. The ancestral population appears to be ACE2 binding, and has a global distribution. Some small clades in a specific region do not have ACE-2 binding. The most parsimonious explanation is that the small clades are derived from the global population.
                                Disagree, as cited
                                Glendower: I can call spirits from the vasty deep.
                                Hotspur: Why, so can I, or so can any man;
                                But will they come when you do call for them? Shakespeare’s Henry IV, Part 1, Act III:

                                go with the flow the river knows . . .

                                Frank

                                I do not know, therefore everything is in pencil.

                                Comment

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