A bombshell that wasn’t

Yesterday, a friend sent me the following

” Chinese Coronavirus Is a Man Made Virus According to Luc Montagnier the Man Who Discovered HIV

Contrary to the narrative that is being pushed by the mainstream that the COVID 19 virus was the result of a natural mutation and that it was transmitted to humans from bats via pangolins, Dr Luc Montagnier the man who discovered the HIV virus back in 1983 disagrees and is saying that the virus was man made.”

Pretty impressive isn’t it?  Montagnier says that in the 30,000 nucleotide sequence of the new coronovirus SARS-CoV-2 he found sequences of the AIDS virus (HIV1).  Worse, the biolab in Wuhan was working both on HIV1 and coronaviruses.  It seems remote that a human could have been simultaneously infected with both, but these things happen all the time in the lab, intentionally or not.

It really wouldn’t take much to prove Montagnier’s point.  Matching 20 straight nucleotides from HIV1 to the Wuhan coronavirus is duck soup now that we have the sequences of both.  HIV1 has a genome with around 10,000 nucleotides, and the Wuhan coronavirus has a genome of around 30,000.  Recall that each nucleotide can be one of 4 things: A, U, G, C.  In the genome the nucleotides are ordered, and differences in the order mean different things — consider the two words united and untied.

Suppose Montagnier found a 20 nucleotide sequence from HIV1 in the new coronavirus genome. How many possibilities are there for such a sequence?  Well for a 2 nucleotide sequence there are 4 x 4 == 4^2 = 16,  for a 3 nucleotide sequence 4 x 4 x 4 == 4^3 = 64.  So for 20 nucleotides there are 4^20 possible sequences == 1,099,511,622,776 different possibilities.  So out of the HIV1 genome there are 10,000 – 20 such sequences, and in the coronavirus sequence there are 30,000 -20  such sequences so there are 10,000 times 30,000 ways for a 20 nucleotide sequence to match up between the two genomes.  That 300,000,000 ways for a match to occur by chance — or less than .1%.  If you’re unsatisfied with those odds than make the match larger.  25 nucleotides should satisfy the most skeptical.

But there’s a rub — as Carl Sagan has said  “Extraordinary claims require extraordinary evidence.”  Apparently Montagnier hasn’t published the sequence of HIV1 he claims to have found in the coronavirus.   If anyone knows what it is please write a comment.

Then there’s the fact that Montagnier appears to have gone off his rocker. In 2009 he published a  paper (in a journal he apparently built) which concludes that diluted DNA from pathogenic bacterial and viral species is able to emit specific radio waves” and that “these radio waves [are] associated with ‘nanostructures’ in the solution that might be able to recreate the pathogen”.

Sad.  Just as one of the greatest chemists of the 20th century will be remembered for his crackpot ideas about vitamin C (Linus Pauling), Montagnier may be remembered for this.

On second thought, there is no reason to need Montagnier and his putative sequence at all. The sequences of both genomes are known.     Matching any 20 nucleotide sequence from HIV1 to any of the 30,000 – 20 20 nucleotide sequences from the Wuhan flu is a problem right out of Programming 101.  It’s a matter of a few loops, if thens and go to’s.  . If you’re ambitious  you could start with smaller sequences say 5 – 10 nucleotides, find a match, move to the next largest size sequence and repeat until you find the largest contiguous sequence of nucleotides in HIV1 to be found in the coronavirus.

You can read about the Wuhan lab in an article from Nature in 2017 — https://www.nature.com/news/inside-the-chinese-lab-poised-to-study-world-s-most-dangerous-pathogens-1.21487

The chemical ingenuity of the AIDs virus

Pop quiz:  You are a virus with under 10,000 nucleotides in your genome.  To make the capsid enclosing your genome, you need to make 250 hexamers of a particular protein.  How do you do it?

 

Give up?

 

You grab a cellular metabolite with a mass under 1,000 Daltons to bind the 6 monomers together.  The metabolite occurs at fairly substantial concentrations (for a metabolite) of 10 – 40 microMolar.

What is the metabolite?

Give up?

 

It has nearly perfect 6 fold symmetry.

 

Still give up?

[ Nature vol. 560 pp. 509 – 512 ’18 ]  https://www.nature.com/articles/s41586-018-0396-4 says that it’s inositol hexakisphosphate (IP6)  — nomenclature explained at the end. http://www.refinebiochem.com/pages/InositolHexaphosphate.html

Although IP6 looks like a sugar (with 6 CHOH groups forming a 6 membered ring), it is not a typical one because it is not an acetal (no oxygen in the ring).  All 6 hydroxyls of IP6 are phosphorylated.  They bind to two lysines on a short (21 amino acids) alpha helix found in the protein (Gag which has 500 amino acids).  That’s how IP6 binds the 6 Gag proteins together. The paper has great pictures.

It is likely that IP6 is use by other cellular proteins to form hexamers (but the paper doesn’t discuss this).

IP6 is quite symmetric, and 5 of the 6 phosphorylated hydroxyls can be equatorial, so this is likely the energetically favored conformation, given the bulk (and mass) of the phosphate group.

I think that the AIDS virus definitely has more chemical smarts than we do.  Humility is definitely in order.

Nomenclature note:  We’re all used to ATP (Adenosine TriPhosphate) and ADP (Adenosine DiPhosphate) — here all 3 or 2 phosphates form a chain.  Each of the 6 hydroxyls of inositol can be singly phosphorylated, leading to inositol bis, tris, tetrakis, pentakis, hexakis phosphates.  Phosphate chains can form on them as well, so IP7 and IP8 are known (heptakis?, Octakis??)

Scary stuff

While you were in your mother’s womb, endogenous viruses were moving around the genome in your developing developing brain according to [ Neuron vol. 85 pp. 49 – 59 ’15 ].

The evidence is pretty good. For a while half our genome was called ‘junk’ by those who thought they had molecular biology pretty well figured out. For instance 17% of our 3.2 gigaBase DNA genome is made of LINE1 elements. These are ‘up to’ 6 kiloBases long. Most are defective in the sense that they stay where they are in the genome. However some are able to be transcribed into RNA, the RNA translated into proteins, among which is a reverse transcriptase (just like the AIDS virus) and an integrase. The reverse transcriptase makes a DNA copy of the RNA, and the integrates puts it back into the genome in a different place.

Most LINE1 DNA transcribed into RNA has a ‘tail’ of polyAdenine (polyA) tacked onto the 3′ end. The numbers of A’s tacked on isn’t coded in the genome, so it’s variable. This allows the active LINE1’s (under 1/1,000 of the total) to be recognized when they move to a new place in the genome.

It’s unbelievable how far we’ve come since the Human Genome Project which took over a decade and over a billion dollars to sequence a single human genome (still being completed by the way filling in gaps etc. etc [ Nature vol. 517 pp. 608 – 611 ’15 ] using a haploid human tumor called a hydatidiform mole ). The Neuron paper sequenced the DNA of 16 single neurons. They found LINE1 movement in 4

Once a LINE1 element has moved (something very improbable) it stays put, but all cells derived from it have the LINE1 element in the new position.

They found multiple lineages and sublineages of cells marked by different LINE1 retrotransposition events and subsequent mutation of polyA microsatellites within L1. One clone contained thousands of cells limited to the left middle frontal gyrus, while a second clone contained millions of cells distributed over the whole left hemisphere (did they do whole genome on millions of cells).

There is one fly in the ointment. All 16 neurons were from the same ‘neurologically normal’ individual.

Mosaicism is a term used to mean that different cells in a given individual have different genomes. This is certainly true in everyone’s immune system, but we’re talking brain here.

Is there other evidence for mosaicism in the brain? Yes. Here it is

[ Science vol. 345 pp. 1438 – 1439 ’14 ] 8/158 kids with brain malformations with no genetic cause (as found by previous techniques) had disease causing mutations in only a fraction of their cells (hopefully not brain cells produced by biopsy). Some mosaicism is obvious — the cafe au lait spots of McCune Albright syndrome for example. DNA sequencing takes the average of multiple reads (of the DNA from multiple cells?). Mutations foudn in only a few reads are interpreted as part of the machine’s inherent error rate. The trick was to use sequencing of candidate gene regions to a depth of 300 (rather than the usual 50 – 60).

It is possible that some genetically ‘normal’ parents who have abnormal kids are mosaics for the genetic abnormality.

[ Science vol. 342 pp. 564 – 565, 632 -637 ’13 ] Our genomes aren’t perfect. Each human genome contains 120 protein gene inactivating variants, with 20/120 being inactivated in both copies.

The blood of ‘many’ individuals becomes increasingly clonal with age, and the expanded clones often contain large deletions and duplications, a risk factor for cancer.

Some cases of hemimegalencephaly are due to somatic mutations in AKT3.

30% of skin fibroblasts ‘may’ have somatic copy number variations in their genomes.

The genomes of 110 individual neurons from the frontal cortex of 3 people were sequenced. 45/110 of the neurons had copy number variations (CNVs) — ranging in size from 3 megaBases to a whole chromosome. 15% of the neurons accounted for 73% of of the CNVs. However, 59% of neurons showed no CNVs, while 25% showed only 1 or 2.