Free The Violinist's Thumb: And Other Lost Tales of Love, War, and Genius, as Written by Our Genetic Code by Sam Kean Page B

glowed raw red “like whale meat” and pierced him with pain. And as badly as Yamaguchi and others suffered during those months, geneticists feared the long-term agony would be equally bad, as mutations slowly began surfacing.
    Scientists had known about mutations for a half century by then, but only work on the DNA → RNA → protein process by the Tie Club and others revealed exactly what these mutations consisted of. Most mutations involve typos, the random substitution of a wrong letter during DNA replication: CAG might become CCG, for instance. In “silent” mutations, no harm is done because of the DNA code’s redundancy: the before and after triplets call for the same amino acid, so the net effect is like mistyping
grey
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But if CAG and CCG lead to different amino acids—a “missense” mutation—the mistake can change a protein’s shape and disable it.
    Even worse are “nonsense” mutations. When making proteins, cells will continue to translate RNA into amino acids until they encounter one of three “stop” triplets (e.g., UGA), which terminate the process. A nonsense mutation accidentally turns a normal triplet into one of these stop signs, which truncates the protein early and usually disfigures it. (Mutations can also undostop signs, and the protein runs on and on.) The black mamba of mutations, the “frameshift” mutation, doesn’t involve typos. Instead a base disappears, or an extra base squeezes in. Because cells read RNA in consecutive groups of three, an insertion or deletion screws up not only that triplet but every triplet down the line, a cascading catastrophe.
    Cells usually correct simple typos right away, but if something goes wrong (and it will), the flub can become permanently fixed in DNA. Every human being alive today was in fact born with dozens of mutations his parents lacked, and a few of those mutations would likely be lethal if we didn’t have two copies of every gene, one from each parent, so one can pick up the slack if the other malfunctions. Nevertheless all living organisms continue to accumulate mutations as they age. Smaller creatures that live at high temperatures are especially hard hit: heat on a molecular level is vigorous motion, and the more molecular motion, the more likely something will bump DNA’s elbow as it’s copying. Mammals are relatively hefty and maintain a constant body temperature, thankfully, but we do fall victim to other mutations. Wherever two T’s appear in a row in DNA, ultraviolet sunlight can fuse them together at an odd angle, which kinks DNA. These accidents can kill cells outright or simply irritate them. Virtually all animals (and plants) have special handyman enzymes to fix T-T kinks, but mammals lost them during evolution—which is why mammals sunburn.
    Besides spontaneous mutations, outside agents called mutagens can also injure DNA, and few mutagens do more damage than radioactivity. Again, radioactive gamma rays cause free radicals to form, which cleave the phosphate-sugar backbone of DNA. Scientists now know that if just one strand of the double helix snaps, cells can repair the damage easily, often within an hour. Cells have molecular scissors to snip out mangled DNA, and can run enzymes down the track of the undamaged strandand add the complementary A, C, G, or T at each point. The repair process is quick, simple, and accurate.
    Double-strand breaks, though rarer, cause direr problems. Many double breaks resemble hastily amputated limbs, with tattered flaps of single-stranded DNA hanging off both ends. Cells do have two near-twin copies of every chromosome, and if one has a double-strand break, cells can compare its ragged strands to the (hopefully undamaged) other chromosome and perform repairs. But this process is laborious, and if cells sense widespread damage that needs quick repairs, they’ll often just slap two hanging flaps together wherever a few bases line up (even if the rest don’t), and hastily fill in the