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
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
- p020 1871 Johannes Mischner "nuclein", later DNA
- Thomas Hunt Morgan fruitflies (Nobel 1933) Columbia, to Caltech 1928
- Hermann Muller ( Nobel 1946 for radiation mutation)
p60 RNA Tie Club 24 physicists and biologists: many baroque models for DNA -> RNA -> Protein
- p77 Zipf's law: word frequency inversely proportional to frequency ordering, p79 ditto for proteins
- p82 grawlix (symbols for swearing)
- Sister Miriam Michael Stimson - shapes of DNA bases in 1940s - errors, but developed infrared imaging of bases
- p103 Lynn Margulis, endosymbiosis
- p106 Microbes without mitochondria use 75% of energy for protein synthesis, no extra for novelties
p108 Barbara McClintock, maize. Cornell instructor 1927, Cold Spring 1941.
- p112 1950, jumping genes letter, chromosome regulation, controversy after 1951
- p118 William Barentz, polar bear liver vitamin A poisoning (vitamin A retinol regulates cell growth, too much and body organs and skin fails)
- p131 methyls stick mostly to cytosine
- p139 1909 Rockefeller Institute - Francis Rous, viral initiated cancer in chickens
- p143 Human genome 8% virus, 2% "human"
- p146 Jack and Donna Wright, 700 cats, toxoplasma gondii makes cat urine attractive
- p158 Philadelphia translocation, DNA swap between non-twinned chromosomes
- p163 Placental embryos may be using retrovirus "fusion" proteins
- p179 Ilya Ivanovic Ivanov attempted Chimp/Human crossbreeds in 1920s
- p183 split was 7MYA, some interbreeding 6MYA
- p185 Human-Chimp X chromosomes more alike than other chromosomes
- p193 probably not, humans 23 pairs chimps 24, different DNA regulation
- p196 consanguous family in China with 22 pairs
- p205 Human apoE mutated from chimps "boosted performance of" (macrophages), protect against inflammation
- p206 "left our arteries looking lie the insides of Crisco cans"
- second mutation appeared 220,000 years ago, helped break down fats and cholesterol
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