A few years ago the
New York Times ran a story about some people who seemed immune to developing adult diabetes. Like me, they were old and overweight, but otherwise relatively healthy. After screening many thousands of people in Sweden, Finland, and Iceland, researchers discovered a strong statistical association with a mutant copy of a gene for a protein dubbed ZnT8. What did the beneficial mutation do at the crucial molecular level? “The mutation
destroys a gene used by pancreas cells where insulin is made” (emphasis added).
44 Another story the same year on the front page of the same paper told of a large study of people with a mutant gene named APOC3, who also had substantially lower cholesterol levels, shielding them from heart attacks: “The scientists found four mutations that
destroyed the function of this gene” (emphasis added).
45 Unsurprisingly, both stories emphasized the medical angle.
I should point out that neither of the analyses above studied actual human evolution—they concerned only contemporary cases. Nonetheless, they are both fine illustrations of the benefits of breaking genes.
46 One case that does concern real, if rather humble, human evolution is that of a mutation in a gene involved with the production of earwax, thought to have arisen more than fifty thousand years ago.
47 In case you didn’t know, earwax is categorized into two general types: wet (favored in warm climates) and dry (favored in cold climates). The mutation that results in dry earwax occurs in a gene dubbed ABCCII. It substitutes one amino-acid residue for another, which destroys the ability of the protein coded by the gene to work.
48 Whether it’s diabetes, heart attacks, or the wrong kind of earwax, very often the quickest way for Darwinian evolution to mitigate a problem is to break something.
Next to people, we arguably are most interested in man’s best friend, since we’ve apparently made so much effort to shape and select dogs over the centuries. In his review in the
New York Times of my second book (he didn’t like it), Richard Dawkins pointed to dog breeds as the premier example of the power of selection (albeit by humans, not nature) to shape animals as if they were so many lumps of plastic
49 (
Fig. 7.2). But, at the DNA level, what exactly are the mutations behind the wide variety of dogs?
Largely degradative. Although they are very hard to track down, here are at least some of the known genetic changes:
50
Increased muscle mass in some breeds derives from degradation of a myostatin gene.
51
Yellow coat color is due to loss-of-FCT of melanocortin 1 receptor; black coat to deletion of a glycine residue from β-defensin.
52
Coat “furnishings” such as long or curly fur come from mutations likely damaging to three separate genes.
53
Six different genes control much of the variation in the size of dogs.
54 Half of them have likely degrading changes in the protein-coding region of the gene; the other three have tweaks in control regions that probably diminish the amount of protein made. All the mutant genes decrease the size of a dog.
Short muzzle is associated with mutations in the genes THBS2 and SMOC2
, which probably lessen their
activity,
55 and with a point mutation in BMP3 that likely damages the protein.
56
White spotting results from small tweaks that decrease the activity of the MITF regulatory region.
57
Short tails are associated with loss-of-FCT ["loss of function"] of the protein coded by a single copy of the mutated T gene.
58 Two copies of the mutated gene are lethal to a dog before birth.
Even the lovable friendliness of dogs toward humans (compared to rather less friendly wolves) is associated with the disruption of genes GTF2I and GTF2IRD1, whose destruction in humans leads to outgoing personalities plus mental disability.59
