5 ms·

No, I'm not doing that. We might not yet have sampled the intermediate steps, if they exist, but it's inevitable that we will do so if it has a natural origin.

by rleigh 5y ago

No, I'm not doing that. We might not yet have sampled the intermediate steps, if they exist, but it's inevitable that we will do so if it has a natural origin. Given the phylogenetic distance between the omicron cluster and its root in the phylogenetic tree, there should be several hundred to thousand intermediates if it's naturally occurring, of which we should be sampling many dozens (modulo selective pressure and sample availability biasing the sampling). Assuming that mutations occur randomly and with equal probability, then you would naively expect if the distance is between the cluster and the root is n base pair changes, then there would be n raised to the fourth power variants (assuming equal selective pressure). The reality is a bit more subtle than that, but I hope it illustrates the general scope and scale of what has taken place here. Given that scope and scale, the complete lack of any sequence data to date is astonishing. Particularly when we do see all those intermediate states for the other variants. Does that make sense? As for variants in animals, that's a possibility. But it's more likely to be a red herring. Domestic animals will be infected with the same strain as their owners, and any reinfection would be very likely to be similar to the original. Transfer to a wild animal reservoir and back into the human population is so rare and unlikely that it is barely credible. Infection of humans from wild animal reservoirs is a rare event. To have it happen both ways within 12 months is not credible. I could be wrong. This will only be answered by collecting more data to improve our understanding.

croes 5y ago
Why should it be inevitable? How long do non dominant variants survive inside and outside a host? We don't even know in which country omicron originated even less who was patient zero. We could easily miss whole strains of the virus but because non of them lead to a new dominant variant we never know the even existed.
- rleigh 5y ago
  It's inevitable because even though one variant may become dominant, there will still be isolated pockets of the other variants. It's very unlikely that these variants will be entirely eliminated across the whole globe. Look at the epidemiology of HIV and the spatial distribution of variants as a point of comparison. Likewise for other viruses. Even if these other variants continue to evolve from the initial root, they will still be phylogenetically distinct from the current omicron clustering, somewhere intermediate between the root and existing omicron cluster. If it's out there in the wild, it will be picked up by PCR eventually. If it's not out in the wild, that big gap will remain, and a lab somewhere has questions to answer... The starting point for the omicron cluster would be an interesting bit of information, but it doesn't necessarily have any bearing on where the intermediate strains are located. But none of that matters. If it's out there, it will eventually be picked up by PCR. We can use phylogenetic analysis to retrospectively reconstruct the evolutionary tree of every organism we have sequenced to date. Doing it just for the coronavirus variants is not hard (I have done it in the past including bootstrapping). Whether it's a month, a year or a decade from now, we will be able to answer the question by reconstructing the tree. This is really basic bioinformatic analysis, in routine use for over two decades. None of this stuff is remotely new or groundbreaking. The other questions you are asking are not really relevant to the problem. The virus does not survive long outside a host; it has no bearing upon the problem at all. The same applies to inside the host. All variants will continue to infect and propagate themselves to varying degrees within the host populations. It's endemic at this point. One other point to bear in mind is that the mutation rate of the polymerase is effectively a constant, in terms of mutations per n kilobases. So we would expect all variants to accumulate a certain number of mutations averaged over time--the sequence will not remain static since the virus has to continually be passaged through mammalian epithelial cells to maintain and propagate itself. There will be some variation, but if it's been frozen down and manually propagated, it may have a dramatically different number of mutations compared with the other contemporary strains that have spent most of their time in living hosts.

by rleigh 5y ago

croes 5y ago

Why should it be inevitable? How long do non dominant variants survive inside and outside a host? We don't even know in which country omicron originated even less who was patient zero. We could easily miss whole strains of the virus but because non of them lead to a new dominant variant we never know the even existed.

rleigh 5y ago
It's inevitable because even though one variant may become dominant, there will still be isolated pockets of the other variants. It's very unlikely that these variants will be entirely eliminated across the whole globe. Look at the epidemiology of HIV and the spatial distribution of variants as a point of comparison. Likewise for other viruses. Even if these other variants continue to evolve from the initial root, they will still be phylogenetically distinct from the current omicron clustering, somewhere intermediate between the root and existing omicron cluster. If it's out there in the wild, it will be picked up by PCR eventually. If it's not out in the wild, that big gap will remain, and a lab somewhere has questions to answer... The starting point for the omicron cluster would be an interesting bit of information, but it doesn't necessarily have any bearing on where the intermediate strains are located. But none of that matters. If it's out there, it will eventually be picked up by PCR. We can use phylogenetic analysis to retrospectively reconstruct the evolutionary tree of every organism we have sequenced to date. Doing it just for the coronavirus variants is not hard (I have done it in the past including bootstrapping). Whether it's a month, a year or a decade from now, we will be able to answer the question by reconstructing the tree. This is really basic bioinformatic analysis, in routine use for over two decades. None of this stuff is remotely new or groundbreaking. The other questions you are asking are not really relevant to the problem. The virus does not survive long outside a host; it has no bearing upon the problem at all. The same applies to inside the host. All variants will continue to infect and propagate themselves to varying degrees within the host populations. It's endemic at this point. One other point to bear in mind is that the mutation rate of the polymerase is effectively a constant, in terms of mutations per n kilobases. So we would expect all variants to accumulate a certain number of mutations averaged over time--the sequence will not remain static since the virus has to continually be passaged through mammalian epithelial cells to maintain and propagate itself. There will be some variation, but if it's been frozen down and manually propagated, it may have a dramatically different number of mutations compared with the other contemporary strains that have spent most of their time in living hosts.