The Violinist's Thumb

And other Lost tales of Love, War, and Genius, as Written By Our Genetic Code

Sam Kean 2012 Little Brown Bvtn 572.8 KEA

Note to Sam Kean

Kean focuses on scientific history and personalities, with some interesting science along the way. Amusing and snarky.

Asterisks in the text indicate notes (digressions, really) in the back of the book.

The "thumb" is for Niccolo Paganini's (1782–1840) incredibly flexible hands. Possibly due to Ehlers-Danlos Syndrome, which limits collagen production.

Random Notes

Sam Kean, I beg to differ: Kean may be misled by the interpretations of apoE function in Finch and Stanford, "Meat Adaptive Genes and the Evolution of Slower Aging in Humans" (2004)

apoE is the ligand on the LDL cholesterol particle, which is the molecular key to the receptor lock. apoE4 is the ancestral ligand, closest to chimpanzee. apoE3 evolved recently, and hasn't completely replaced apoE4 yet.

Cholesterol is a necessary building block for animal cell membranes, and comprises 40% of the human brain by dry weight, as it is the principal component of myelin. Human blood vessels damaged by high glycemic diets repair themselves using cholesterol, however, the repairs patch the insides of the vessels, restricting flow. So, the liver makes more LDL if more is needed. But it also makes more if the LDL is poorly absorbed.

What if the LDLR receptor also evolved between simian and human, from a hypothetical ancestral "LDLR4" to a new "LDLR3"? What would select for that?

Premature aging is a minor problem, weak selection pressure. Avoiding fatal bacterial/viral infection before reproduction is a major problem. Some pathogens, like HSV1, enter cells through the LDL receptor. Evolving a receptor that thwarts pathogen entry has strong selective value, even if cholesterol transport becomes less efficient; the liver has enough nutrients to make more. So, an evolution to "LDLR3" can prevent infection, even if it results in fewer grandmothers. Grandmothers (while not essential) are useful, so when the apoE4 to apoE3 mutation occurred, it provided a selective advantage and spread, in environments where grandmothers did not die of starvation.

This is hypothetical, but testable. There are individuals with LDLR allele differences who suffer from hypercholesteremia. Let's call that allele "LDLRx". If LDLRx plus apoE4 does not result in hypercholesteremia, then LDLRx may be a good candidate for the ancestral allele LDLR4. That is because LDLR and apoE match, allowing the more efficient cholesterol transport.

Another test could come from molecular-scale modelling of the apoE ligand and the LDLR receptor. The single-codon difference between apoE4 and apoE3 results in an arginine replaced by a cysteine at protein position 158; that changes the shape and the change configuration on the molecule


ViolinistThumb (last edited 2016-11-22 23:05:27 by KeithLofstrom)