An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots...

[intrepidity]

https://academic.oup.com/mbe/advance-article/doi/10.1093/molbev/msab118/6257226

ACCEPTED MANUSCRIPT

An evolutionary portrait of the progenitor SARS-CoV-2 and its dominant offshoots in COVID-19 pandemic

Sudhir Kumar, Qiqing Tao, Steven Weaver, Maxwell Sanderford, Marcos A Caraballo-Ortiz, Sudip Sharma, Sergei L K Pond, Sayaka Miura

Molecular Biology and Evolution, msab118, https://doi.org/10.1093/molbev/msab118

Published: 04 May 2021

Abstract
Global sequencing of hundreds of thousands of genomes of Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, has continued to reveal new genetic variants that are the key to unraveling its early evolutionary history and tracking its global spread over time. Here, we present the heretofore cryptic mutational history and spatiotemporal dynamics of SARS-CoV-2 from an analysis of thousands of high-quality genomes. We report the likely most recent common ancestor of SARS-CoV-2, reconstructed through a novel application and advancement of computational methods initially developed to infer the mutational history of tumor cells in a patient. This progenitor genome differs from genomes of the first coronaviruses sampled in China by three variants, implying that none of the earliest patients represent the index case or gave rise to all the human infections. However, multiple coronavirus infections in China and the USA harbored the progenitor genetic fingerprint in January 2020 and later, suggesting that the progenitor was spreading worldwide months before and after the first reported cases of COVID-19 in China. Mutations of the progenitor and its offshoots have produced many dominant coronavirus strains, which have spread episodically over time. Fingerprinting based on common mutations reveals that the same coronavirus lineage has dominated North America for most of the pandemic in 2020. There have been multiple replacements of predominant coronavirus strains in Europe and Asia and the continued presence of multiple high-frequency strains in Asia and North America. We have developed a continually updating dashboard of global evolution and spatiotemporal trends of SARS-CoV-2 spread (http://sars2evo.datamonkey.org/).

[NNadir]

1. I know someone who knows Dr. Kumar well.

He's one of the most interesting people with whom she's every worked, from what I hear very dynamic, creative, hard working and productive, perceptive and quite amusing.

He's been interviewed by major news organizations in connection with this paper, including the Wall Street Journal, and major newspapers in India.

He has expertise, besides evolutionary biology and viral genetics, in computer science, and even electrical engineering, which is the area in which he got his undergraduate degree.

He gives the best advice to his students, which is, "You have to reinvent yourself every three years. I do."

What she tells me about him impresses the hell out of me.

[intrepidity]

2. That's good to hear.

What do you make of the findings? It has important implications, imho.

[NNadir]

3. As I understand it - and I haven't personally met him but know someone who has -

Dr. Kumar is an expert in data mining and drawing out evolutionary connections from that data.

Although I have worked extensively with proteomic data bases like Swissprot and Uniprot, I have almost no experience in genomic databases. This is mostly connected, in my case, with mass spectrometry. It is somewhat astounding the level of detail in these databases.

In the proteomic case, there are some proteins that are quite unique to specific species and others which are highly conserved across all species, down to the level of single cell organisms right up through whales, and of course, humans.

I have worked on efforts for restoring function to vestigial proteins and have some experience in considering genetic diseases.

If one tracks sequence changes for nearly conserved proteins - I believe this applies to genomes as well - one can draw inferences about the evolutionary path by which they arose. The protein sequence is, of course, dictated by the genomic sequence, post-translational modifications notwithstanding.

My take on this paper, which I have skimmed but not read in great detail, is that the virus has been circulating around the world for sometime, perhaps in a less virulent or contagious form, but may have mutated into more infectious forms in humans. This calls into question, in my mind, whether the virus actually originated in China. China may have presented the first "super spreader" events in Wuhan, and thus Wuhan is thought of as being the progenitor cases. On the other hand, it could have been brought to Wuhan by someone from Malaysia on a business trip.

As I read it, and perhaps I read it wrong, "case zero" is still a mystery.

As I understand it, this virus is somewhat unusual inasmuch as unlike many other RNA viruses, it has a primitive transcription correction protein.

Nevertheless, we are clearly seeing the evolution of the virus in humans around the world, and in some cases, more aggressive and contagious variants have arisen far from China. To me this suggests the possibility that the progenitor of this disease originated, in fact, in a human being, perhaps infected a long time ago by interspecies transfer with a less than virulent form.

Happily none of these variants has proved capable of completely surmounting the existing vaccines. As I have more than passing familiarity with the technology applied for the vaccines, I am quite sure that the infrastructure exists to generate new vaccines quickly as needed. This technology is very impressive and very powerful.

It's possible, with some luck, I will have occasion to meet Dr. Kumar, and if so, I will ask him for his opinion on all of this. I'd love to meet him, because what I hear of him is fascinating.

I also attended an online lecture today about the immunological implications of the virus, in which the speaker, who was involved in the the discovery of MHC/peptide complexes connected with the recognition of foreign bodies by killer T-Cells, Seth Lederman, explained that antibodies are probably less effective in Covid control than are T-Cells. Whether this is true or not, I am unqualified to say.

My understanding of immunology is rather primitive, and most of what I know comes purely from osmosis. This is also true of Dr. Kumar's work. I know enough to get in trouble about virology, and the genomics of evolution but I am hardly an expert. I know what an SNP is, and I encounter them from time to time in my work, but not enough to be expert on their implications.

It does seem that there is still a lot of questions unanswered about the origins of Covid and my feeling is that wild speculations about this matter probably do more harm than good.

I would be disgusted, for example, if people went on a crusade to wipe out bats because they are suspected at the originating species.

I hear a lot of claims about lab origins, but I very much doubt they have any substance; I regard them as a function of our conspiracy theory laced times, times which I attribute to the very real downsides of the internet. Information without critical thinking can be and often is quite dangerous.

It is better to say "I don't know," than to share what someone has heard on the internet without doing any verification.

[intrepidity]

4. I *always* appreciate your detailed answers

So, thank you