When does a description of something become an explanation ?

“It’s just evolution”. I found this explanation of the molecular biology underlying our brain’s threefold expansion relative to the chimp extremely unsatisfying.  The molecular biology of part of the expansion is fascinating and beautifully worked out. For details see a copy of the previous post below the ***.

To say that these effects are ‘just evolution’ is using the name we’ve put on the process to explain the process itself, e.g.  being satisfied with the description of something as an explanation  of it.

Newton certainly wanted more than that for his description of gravity (the inverse square law, action at a distance etc. etc.) brilliant and transformative though it was.  Here he is in a letter to Richard Bentley

“That gravity should be innate inherent & {essential} to matter so that one body may act upon another at a distance through a vacuum without the mediation of any thing else by & through which their action or force {may} be conveyed from one to another is to me so great an absurdity that I believe no man who has in philosophical matters any competent faculty of thinking can ever fall into it. ”

But the form of the force law for gravity combined with Newton’s three laws of motion (1687) became something much more powerful, a set of predictions of phenomena as yet unseen.

The Lagrange points are one example.  They are points of equilibrium for small-mass objects under the influence of two massive bodies orbiting their common center of gravity.  The first Lagrange points were found by Euler in 1750, Lagrange coming in 10 years later.  One of the Lagrange points of the Earth Sun  system is where the James Webb telescope sits today remaining stable without expending much energy to keep it there.  In a rather satisfying sense the gravitational force law explains their existence (along with Newton’s laws of motion and a lot of math).  So here is where a description (the force law) is actually an explanation of something else.

But Newton wanted more, much more than his description of the gravitational force (the inverse square law).  It took Einstein centuries later to come up with General Relativity — the theory of the gravitational force.  Just as a ball rolls down an incline here under the force of gravity, planets roll down the shape of Einstein’s spacetime, which is put there by the massive bodies it contains.  By shaping space everywhere, masses give the illusion of force, no action at a distance is needed at all.

It is exactly in that sense that I find the explanation for the 8 million year scuplting of our brain as evolution unsatisfying.  It is essential a description trying to pass itself off as an explanation.  Perhaps there is no deeper explanation of what we’re finding out.  Supernatural explanations have been with us in every culture.

Hopefully if such an explanation exists, we won’t have to wait over two centuries for it as did Newton.

*****

The evolutionary construction and magnification of the human brain

Our brains are 3 times the size of the chimp and more complex.  Now that we have the complete genome sequences of both (and other monkeys) it is possible to look for the protein coding genes which separate us.

First some terminology.  Not every species found since the divergence of man and chimp is our direct ancestor.  Many banches are extinct.  The whole group of species are called hominins [Nature vol. 422 pp. 849 – 857 ‘ 03 ].  Hominids are species in the path between us and the chimp — sort of a direct line of descent.  However the terminology is in flux and confusing and I’m not sure this is right.   But we do need some terminology to proceed.

Hominid Specific genes (HS genes) result which result from recent gene duplications in hominid/human genomes.  Gene duplication is a great way for evolution to work quickly.  Even if one gene is essential, messing with the other copy won’t be fatal.  HS genes include >20 gene families that are dynamically expressed during the formation of the human brain.  It was hard for me to find out just how many HS genes there are.

Here are some examples. The human-specific NOTCH2NL genes increase the self-renewal potential of human cortical progenitors (meaning more brain cell can result from them).  TBC1D3and ARGHAP11B, are involved in basal progenitor amplification (ditto).

A recent paper [ Neuron vol. 111 pp. 65 – 80 ’23 ] discusses CROCCP2 (you don’t want to know what the acronym stands for) which is one of several genes in this family with at least 6 copies in various hominid genomes.  However, CROCCP2 is a duplicate unique to man.   It is highly expressed during brain development and enhances outer Radial Glial Cell progenitor proliferation.

The mechanism by which this happens is detailed in the paper and involves the cilium found on every neuron, mTOR, IFT20 and others.

But that’s not the point here, fascinating although these mechanisms are.   We’re watching a series of at least 20 gene duplications with subsequent modifications build the brain that is unique to us over relatively rapid evolutionary times.  The split between man and chimp is thought to have happened only 8 million years ago.

What should we call this process?  Evolution?  The Creator in action? The Blind Watchmaker?   It is certainly is eerie to think about.  There are 17 more HS genes to go involving in building our brains remaining to be worked out.  Stay tuned

 

The evolutionary construction and magnification of the human brain

Our brains are 3 times the size of the chimp and more complex.  Now that we have the complete genome sequences of both (and other monkeys) it is possible to look for the protein coding genes which separate us.

First some terminology.  Not every species found since the divergence of man and chimp is our direct ancestor.  Many banches are extinct.  The whole group of species are called hominins [Nature vol. 422 pp. 849 – 857 ‘ 03 ].  Hominids are species in the path between us and the chimp — sort of a direct line of descent.  However the terminology is in flux and confusing and I’m not sure this is right.   But we do need some terminology to proceed.

Hominid Specific genes (HS genes) result which result from recent gene duplications in hominid/human genomes.  Gene duplication is a great way for evolution to work quickly.  Even if one gene is essential, messing with the other copy won’t be fatal.  HS genes include >20 gene families that are dynamically expressed during the formation of the human brain.  It was hard for me to find out just how many HS genes there are.

Here are some examples. The human-specific NOTCH2NL genes increase the self-renewal potential of human cortical progenitors (meaning more brain cell can result from them).  TBC1D3and ARGHAP11B, are involved in basal progenitor amplification (ditto).

A recent paper [ Neuron vol. 111 pp. 65 – 80 ’23 ] discusses CROCCP2 (you don’t want to know what the acronym stands for) which is one of several genes in this family with at least 6 copies in various hominid genomes.  However, CROCCP2 is a duplicate unique to man.   It is highly expressed during brain development and enhances outer Radial Glial Cell progenitor proliferation.

The mechanism by which this happens is detailed in the paper and involves the cilium found on every neuron, mTOR, IFT20 and others.

But that’s not the point here, fascinating although these mechanisms are.   We’re watching a series of at least 20 gene duplications with subsequent modifications build the brain that is unique to us over relatively rapid evolutionary times.  The split between man and chimp is thought to have happened only 8 million years ago.

What should we call this process?  Evolution?  The Creator in action? The Blind Watchmaker?   It is certainly is eerie to think about.  There are 17 more HS genes to go involving in building our brains remaining to be worked out.  Stay tuned

The pandemic virus as evolution professor

Like it or not, the pandemic virus (SARS-CoV-2) is giving us all lessons in evolution and natural selection. The latest is one of the clearest examples of natural selection you are likely to see.  It is very clear cut, but to leave almost no one behind, I’m going to put in a lot of background material which will bore the cognoscenti — they can skip all this and go to the meat of the issue after the ****

The genetic code is read in groups of 3.  Imagine a language in which all words must be 3 letters long. 

The dog ate the fat cat who bit the toe off one mad rat.   Call this the reading frame, in which the words all make sense to you

Any combination of 3 letters means something to the machinery inside the cell responsible for reading the code, so deleting the f in fat 

gives us 

The dog ate the atc atw hob itt het oeo ffo nem adr at.   So this is a shift of 1 from the reading frame.  While it may not make sense to you, it makes sense to the cellular machinery. 

Now let’s delete 2 letters (in a row)

The dog ate the fat cat who bit the tof fon ema dra t.  

Not much sense after the deletion is there?  Or at least a completely different message.  This is a shift of 2 from the reading frame.

Now 3 letters (in a row)

The dog ate the fat cat who bit the toe off one mad rat.  

This gives 

The dog ate the fat cat who bit the tff one mad rat.  

Which has a funny looking word (tff), but leaves the rest of the 3 letter words intact (one mad rat).  This is called an in frame deletion. It basically lops out a single 3 letter word.  

Lopping out 4, 5, 6, .. letters will just give you one of the 3 patterns (frame shift of 1, frame shift of 2 or no frameshift at all) shown above (but nothing new)

*****

Now the business end of the pandemic virus is the spike protein, and these are where the mutations everyone is worried about occur.  The spike protein binds to another protein (ACE2) on the surface of human cells and then the virus enters causing havoc.  All the vaccines we have are against the spike protein. 

The spike protein is big (1,273 different 3 letter words).  

Mutations occur randomly.  We now have something called GISAID (Global Initiative on Sharing All Influenza Data) which has well over 100,000 genome sequences of the virus.  

Other things being equal we should see as many 1,  4 (3+1), 7 (2*[3] + 1), 10 letter deletions as 2, 5 (3 + 2), 8 ( 2*[3] + 2) , as 3, 6, 9, 12, letter   deletions.

The set  1, 4, 7, 10, . . represents a shift of 1 from the original reading frame, the set 2, 5, 8, 11 … represents a frame shift of two and 3, 6, 9 .. represents a set of deletions producing no frameshift at all.

Since thousands on thousands of experiments show that mutations occur randomly, 1/3 of all deletion mutations should show a frameshift of 1, 1/3 of all deletion mutations should have a frame shift of 2, and 1/3 of all deletion mutations should produce no frameshift at all. 

Well the authors of Science vol. 371 pp. 1139 – 1142 ’21  looked at 146,795 viral sequences and found 1,108 deletions in the gene for the spike protein.

They did not find each of the 3 types of deletions occuring to the same extent (1/3 of the time).  Among all deletions, 93% were in frame.  

Why? Because out of frame deletions change everything that comes after them. 

Recall

The dog ate the atc atw hob itt het oeo ffo nem adr at.  

This means that a functional spike protein won’t be formed, and the virus won’t infect our  cells, and it certainly won’t be found in GISAID.  

Ladies and Gentlemen you have just witnessed natural selection in action. 

Actually it’s even more complicated and even more impressive than that.  The in frame deletions occurred in one of four areas, which happen to be where antibodies to the spike protein bind.  So the out of frame deletions were selected against, and the in frame deletions were selected for. 

The blind watchmaker in action.

Another way to see how improbable it is that random choice should choose one of 3 equally probable possibilities 97% of the time, imagine that you are throwing dice.  You throw a single dye 100 times, and 97 times you get either of two numbers (say 3 and 6) .  You know the dye is loaded.  The load being natural selection in the case of genome deletions.