In 1980, Italian researchers found that a man from Limone sul Garda (a small lakeside village in northern Italy) had very low levels of HDL ("good" cholesterol) and high levels of triglycerides, yet showed no sign of heart disease. Both of his parents
had lived to advanced ages. Their curiosity whetted, the researchers performed blood tests on all 1,000 inhabitants of Limone and found a total of 43 people with this same unusual blood-lipid profile. The local church had birth records going back centuries, and the researchers were able to determine that all those individuals could trace their ancestry back to the same couple (Giovanni Pomaroli and Rosa Giovaneli), who had married in 1780.4 This genealogical pattern suggested that these villagers shared a mutation, which turned out to be a change in the protein called ApoA-I (Apolipoprotein A-I), a major component of high-density lipoprotein (HDL). ApoA-I helps to clear cholesterol from arteries, but this variant, ApoA-^ (M for Milano), apparently does a considerably better job of it. A change in a single nucleotide modified an amino acid in the protein, completely changing its chemical action.
ApoA-IM is much more effective at scouring out arteries than the standard version of the protein is, and carriers have substantial protection against atherosclerosis. They have a much-reduced risk of heart attacks and strokes, and they often reached an advanced age.5 Not only that, these effects of the ApoA-IM mutation have been duplicated in mice, and it protects them against artery plaque as well.6 Preliminary tests show that intravenously administered synthetic ApoA-IM actually shrinks preexisting artery plaque in humans: Nothing else we know of does that.
Judging from the records we have, this mutation seems to have increased in number, from 1 copy to 43 in ten generations. Chance and general population growth must have played a role, but let's suppose that freedom from heart attacks and strokes is driving a gradual increase. What would happen if it were given several thousand years to expand?
Let's say that its true advantage—the long-term average— is 7 percent, so that carriers raise 7 percent more children than average. In that case, you'd expect most Europeans to have a copy in 6,000 years or so. This assumes, of course, that Europe will still exist thousands of years from now, that we won't have developed a universal cure for atherosclerosis in the meantime, and that the robots won't have taken over first. We know the future is uncertain—bear with us.
Success in 6,000 years is nothing to hold your breath about, but the point is that mutations with a similar advantage that started in a single village at the dawn of recorded history have had time to become common in just this way. That estimate assumes that genes (and people) are well mixed, but that's clearly not the case in Limone sul Garda. The village is quite isolated: The mountains and the lake hem it in, and there wasn't even a road until the 1930s. Such isolation doesn't make the occurrence of a favorable mutation more or less likely, but the concentration of carriers in one village may have made them easier to notice. However, it certainly interferes with the spread of the gene.
So how did a favorable mutation spread thousands of years ag°?
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