Tuesday, September 15, 2020

On The Origin of the Genes of Viruses - 15

A culture of mania
I. In The Rear View Mirror

I thought I would interrupt the series about the home of Covid-19 (On The Origin Of The Home Of COVID-19, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17) to add a post to an old Dredd Blog series.

It is a series that has up until now dealt with some of the perplexing questions that scientists wonder about concerning how viruses and their genes came into existence in the first place (The Uncertain Gene - 2, On The Origin of the Genes of Viruses).

Now that genetics has become part of the saga, the "genes" part of a virus genome expressed by virologists consists of an arrangement of "bases" ("ACGT") in various sequences ("CATG", "TCGA", "ATGC", etc.) which result in a different viral "look and feel" ... and behavior.

II. Parts Are Parts
Viruses are not living carbon-based life forms like cells that can reproduce themselves.

No, instead they are like other machines in that they require carbon based life forms to reproduce them.

They cannot reproduce themselves; they must be reproduced by biotic, carbon-based life forms (cells).

They, like the other billions of micro-machines in the biotic realm, are abiotic (Weekend Rebel Science Excursion - 27).

Machines are composed of parts (List of auto parts, Spare part, Parts book, List of bicycle parts), thus the virus "genome" is like a parts list.

When parts are combined they may become "equipment" and comprise an equipment list (Master Minimum Equipment List).

So, combinations of virus parts like the "gene" can be compared to equipment that has special functions (carburetor, transmission, axles, wheels, and the like).

Using the word "gene" is a hangover from a couple of hundred years ago when the science was absent of the concept of abiology, and was of the notion that viruses and DNA were alive, were biotic.

An abundance of the viral parts, comprising large parts lists, have been found on the surface of biological cells:

"Typically, the nuclear genome encoded RNAs (ngRNA) are not expected to be present on the surface of eukaryotic cells with intact cell membranes ... [except for 'leakage'] To confirm that the Surface-FISH signals are not a result of RNA leakage from damaged cell membranes, we combined Malat1 Surface-FISH with a transmission-through-dye (TTD) microscopic analysis, where only live cells with intact membranes are fluorescently labeled ... signals appeared on cells with perfectly intact membranes ... [thus, their techniques] suggest the presence of specific nuclear-encoded transcripts on the surface of intact live cells.
(RNA on Cell Surface, emphasis added). That paper is about parts just laying around on the surface of a cell like parts in a junk yard.

But again, viruses are like machines in another aspect, that is, they can modify other machines.

That change, to a certain degree, is automated:
"Genetic instability of microorganisms is an inherent property allowing rapid microbial evolution to adapt to ever changing ecologic niches. This is particularly true of RNA viruses such as influenza viruses, flaviviruses, enteroviruses, and coronaviruses, which have inherently deficient or absent polymerase error correction mechanisms and are transmitted as quasispecies or swarms of many, often hundreds or thousands of, genetic variants. Emergences of viral diseases begin with the genetic plasticity of the infectious agent, which may repeatedly encounter ecologic niches into which it can evolve and adapt under facilitative circumstances, e.g., those provided by the hosts in the context of the host environment. For viruses transmitted by person-to-person mechanisms, transmission by quasispecies may increase the likelihood that one or more viral variants within the quasispecies will be infectious for cells of a new host, leading to infection, viral amplification, and expansion of a new and different quasispecies, facilitating onward transmission ...".
"Major portals of host entry for infectious agents include those that are visibly external to the environment such as the skin or that can be reached directly from the environment such as the respiratory and gastrointestinal tracts, as well as organs reached systemically such as the liver, heart, and other internal organs. Human beings have many different organ systems, each with many different cell types, and with each cell having arrays of different receptors; therefore, it is not surprising that switching of a pathogen from an animal host to humans results in very different clinical and epidemiologic outcomes, including different disease manifestations and transmission mechanisms. These factors ultimately relate to the potential for establishment of infection in the new host as well as the likelihood of sustained transmission within the new host population and, as such,have a bearing on whether host-switching succeeds or fails. SARS-CoV and SARS-CoV-2 enter cells via ACE-2 receptors (Wang et al., 2020), found on lung alveolar epithelial cells, gastrointestinal enterocytes, arterial and venous endothelial cells, and arterial smooth muscle cells, among other cell types (Hamminget al., 2004; Wang et al., 2020), which explains the excretion of SARS-CoV-2 and potential transmission via the respiratory and enteric routes. With regard to the latter, although SARS-CoV-2 infects cells of the gastrointestinal tract, fecal transmission has not to date been implicated in significant person-to-person viral spread.
(How We Got to COVID-19, emphasis added). The "enteric routes" mentioned in that paper goes from the mouth to the anus/rectum (it's the gut microbiome).

The Dredd Blog series "On The Origin Of The Home Of COVID-19" (links are in the first sentence of Section I above) has hypothesized that "the mass-slaughter-of-animals-for-food industry" is a source of the transmission of the genes of viruses (On The Origin Of The Home Of COVID-19-15).

The posts in that series include the hypothesis that the export of slaughtered meat saturated with viral parts is a source of the spread of that tiny, but pathogenic, machine world.

In fact, that human gut filled with food from "the mass-slaughter-of-animals-for-food industry" is an early warning system for Covid-19:
"A surge in internet searches about gut ailments is helping researchers predict the next Covid-19 hotspots, a study has revealed. Massachusetts General Hospital found areas where there was a spike in Google queries relating to diarrhea and loss of appetite frequently reported a sharp rise in cases of coronavirus three to four weeks later. Other markers included a loss of taste, nausea and abdominal pain."
(Internet searches for gut problems provide early warning of Covid-19 hotspots, 'I've had 'gastric coronavirus' for weeks - why is no one talking about this version of the virus?'). The "gastrointestinal tract" used in the medical profession is "scientific Latin" that simply means "the area from where the food goes in, to where the food comes out", i.e. from the mouth to the rectum.

Thus, our diet is the major factor impacting the gastrointestinal realm:
"The composition of the human gut microbiome is determined by many factors. Eran Segal and colleagues performed an extensive statistical analysis of the largest metagenomics-sequenced human cohort so far to determine the contribution of host genotype to microbiome composition. Host genetics has only a minor influence on microbiome variability, which is more strongly associated with environmental factors such as diet. The authors propose a 'microbiome-association index' that describes the association of the microbiome with host phenotype. Combining this measurement with host genetic and environmental data improves the accuracy of predictions about several human metabolic traits, such as glucose and obesity traits."
A wealth of evidence suggests that this incredibly diverse microbial community is regulated by host genetic factors, and more importantly, environmental and dietary factors."
(On The Origin Of The Home Of COVID-19-15). So, it is a logical deduction to say that our research should include a search of the human gut microbiome for "equipment" and "parts" of the viruses that make up the Coronaviridae realm.

III. The Appendices

 The appendices to today's post include searches and comparisons of the Coronaviridae realm (Coronavirus genomes – NCBI Datasets) with the viruses in the GVD (human gut database) ... (GVD Download) (the five largest bases in the GVD are used in the comparisons).

The appendices detail that the "fragmented" residue of Coronaviridae viruses exists in the human gut microbiome.

That is, "equipment" (large segments of the genome ... e.g. "genes") and "parts" (small sections of "equipment") are all over the place in the human gut.

When writing the analysis software, I focused on comparing various machines and parts, that is, comparing the gene bases, the mat_peptide bases, the UTR bases, and the stem_loop bases of the Coronaviridae viruses to the human gut genome machines and parts (could I find the same or relatively similar matches in both genomes?).

Meta Hosts
Porcine 1Appendix 1
Porcine 2Appendix 2
Porcine 3Appendix 3
Porcine 4Appendix 4
Porcine 5Appendix 5
AvianAppendix A
BovineAppendix B

IV. Closing Comments

Today's appendices confirm the extracted quote from the paper linked to in Section I above:
"Genetic instability of microorganisms is an inherent property ... This is particularly true of RNA viruses such as ... coronaviruses, which ... are transmitted as ... genetic variants. Emergences of viral diseases begin with the genetic plasticity ..."
(ibid). The tables in the appendices show that "genetic instability" (which I would rather characterize as "sharing of machine equipment and parts") is apparent because Coronaviridae parts and segments (parts of parts, e.g. nuts & bolts) are spread throughout the human gut microbiome.

This spread of the "equipment" and "parts" of the Coronaviridae realm throughout the human gut microbiome is to be expected according to the hypothesis that "the mass-slaughter-of-animals-for-food industry" makes Coronaviridae by destroying the homes of commensal, mutualistic, and symbiotic viruses because that industry generates the breakup of animal-gut single-celled microbes via antibiotics and other toxins.

Then the spread expands by exporting and selling meat products around the world as food which makes up the diet that goes through the human gut in many places.

So, just to reemphasize it, the diet is the food we eat which they produce:
"The composition of the human gut microbiome is determined by ... environmental factors such as diet ... this measurement with host genetic and environmental data improves the accuracy of predictions about several human metabolic traits, such as glucose and obesity traits ... regulated by ... environmental and dietary factors."
(ibid). These dietary products are then spread around the world via the mass exports of those foods and offal (On The Origin Of The Home Of COVID-19 - 15).

And finally, predictions of Covid-19 outbreaks can be made by analyzing the amount of gastrointestinal (gut) problems questions asked after the food is digested:
"A surge in internet searches about gut ailments is helping researchers predict the next Covid-19 hotspots ..."
(ibid). Remember that the "genes" of viruses are machines or parts thereof (On The Origin Of The Home Of COVID-19 - 17).

The previous post in this series is here.

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