dramatic fashion, was the probable agent of selection. Presumably the loss of 32 units from the gene alters the structure of the surface protein used by both the AIDS virus and the smallpox virus to gain access to a cell. Diseases, especially those that kill people before the age of reproduction, are potent selective forces. So too are genes that affect fertility. A genetic change that favors fertility has been observed at high frequency in European populations. It occurs rarely in Africans but bears the marks of being under strong selection in Europe, as if promoted by something in the European environment. The change consists of a large segment of chromosome 17, some 900,000 DNA units in length, which has become flipped, or inverted. The inversion carries several genes but it is not clear which of them is responsible for conferring greater fertility.^ The inversion evidently rose to high frequency among Europeans after the exodus from Africa and perhaps in the last 10,000 years. From a historical point of view, the most interesting class of evolutionary changes are those that have occurred in response to human culture. When people first started to abandon their way of life as hunters and gatherers some 15,000 years ago, they had much less need for two kinds of gene, the olfactory genes that mediate the sense of smell, and the genes that are used by the liver to detoxify the natural poisons with which wild plants defend themselves. When a gene is vital for an organism's survival, any mutation in the gene will be lethal and the mutated version will be lost from the population. But when mutations crop up in genes that don't matter anymore, the gene may survive, even though it has lost its function. This has been the fate of many human olfactory genes. Mammals possess a standard suite of about 1,000 of these genes. The proteins that each makes are embedded in the surface of the cells that line the nose and serve to detect specific odors. Once people settled down and grew their food, they no longer depended on their noses to detect which fruits were ripe or which wild plants were relatively safe to eat. On evolution's use-it-or-lose-it principle, more than 60% of olfactory genes in people are now inactive. Yoav Gilad and colleagues at the Max Planck Institute for Evolutionary Anthropology in Leipzig find that humans are losing their olfactory receptor genes four times faster than other higher primates. "This process is probably still ongoing in humans," they conclude.^41 Distressing news as this may be to gourmets and oenophiles, the price of civilization is that the faculty of smell is inexorably being degraded. In parallel with the loss of olfactory genes, people are also losing genes that detoxify natural plant poisons. The enzymes made by these genes are no longer needed for their original purpose but have assumed an unexpected role in modern societies—that of metabolizing medicinal drugs. This unnatural stimulus does not occur often enough, however, and many of the genes are being lost through disuse. (This process explains much of the variability in the response to drugs, including why some people have severe side effects or require different doses. People who have lost the gene that breaks down a certain drug will maintain a high dose of it in their bloodstream, whereas those who still retain the gene will clear the drug rapidly.) After settlement and agriculture came the rearing of livestock. Lactose tolerance, as discussed earlier, is the genetic response to the availability of animal milk. The genetic change evolved some 6,000 years ago among cattle herders of northern Europe and later among peoples of Africa and the Near East who took up pastoralism.

Of two recent evolutionary cognitive changes, which are also responses to culture, one is the postulated development of genes for enhanced intelligence among the Ashkenazi Jews of medieval Europe. As noted in the previous chapter, the hypothesis holds that because of the intellectually demanding occupations to which Jews were confined for some 900 years, any mutation that released constraints on the growth of the brain was favored, and that these mutations are the ones familiar as causing a variety of genetic diseases among people of Ashkenazic descent.

The other cognitive change is one that can be inferred from the striking recent rise to prominence of versions of two brain genes. As described in chapter 5, the genes first came to light because mutated versions cause microcephaly, a condition in which people are born with an unusually small head and brain. The new version of the microcephalin gene appeared around 37,000 years ago, rapidly became more common under intense selective pressure, and is now carried by most people in Europe and East 342

Asia. The other gene, a new version of ASPM, emerged 6,000

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