Some mutations have no effect on the organism, or have effects that are not associated with differences in survival or reproduction. Such mutations are considered neutral. Many mutations have neutral effects on organisms because they occur in noncoding DNA. Neutral mutations are therefore especially likely to occur in organisms with large genomes and abundant noncoding DNA (Chapter 13).

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Quick Check 2 Given what you read about the human genome in Chapter 13, would you predict that most mutations in humans are harmful, beneficial, or neutral?

Sometimes common, seemingly harmless genetic variations occur in coding sequences. One example in human populations is the taster phenotype associated with perception of a bitter taste from certain chemicals, including phenylthiocarbamide (PTC). The taster polymorphism was discovered in 1931 when a commercial chemist seeking a new artificial sweetener accidentally released a cloud of fine crystalline PTC and heard his colleague working nearby complain about its bitter taste. The chemist himself tasted nothing. He began testing his own and other families, and set the stage for future genetic studies.

The minimal concentration for PTC tasting varies among individuals, but being able to taste a concentration of 0.5 millimolar or less is often taken as the cutoff between the taster and nontaster phentoypes. In a sample from Utah, the frequency of nontasters is about 30%. This is typical for people of European descent, but the frequency of nontasters differs among populations, from as low as 3% in West Africa to as high as 40% in India.

The ability or inability to taste PTC is due largely, but not exclusively, to alleles of a single gene called TAS2R38 that encodes a taste receptor in the tongue. Nonhuman primates are homozygous for an allele of this gene known as the PAV allele, so called because the protein it encodes has the amino acids proline (P), alanine (A), and valine (V) at specific positions. Humans also have the PAV allele, and PAV/PAV homozygous genotypes are almost all tasters.

The most common allele associated with the nontaster phenotype is AVI, in which the amino acids in the taste receptor are alanine (A), valine (V), and isoleucine (I) instead of proline, alanine, and valine. About 80% of homozygous AVI/AVI genotypes are nontasters. One copy of the PAV allele is usually sufficient for the taster phenotype; about 98% of PAV/AVI heterozygous genotypes are tasters.

The factors contributing to the taster phenotype are more complex than a genotype at a single gene, however. The AVI/AVI genotype tips the balance toward the nontaster phenotype, but not completely. Other genes and the environment also play a role.

Why is this strange variation present in the human population? One hypothesis is that an aversion to compounds that contain a thiourea group (N–C=S), as PTC does, may discourage eating certain plants that produce poisonous defense compounds. One class of such compounds is the glycosinolates, which are present in many wild plants and some cultivated vegetables, including broccoli, watercress, turnip, and horseradish. Sure enough, PAV/PAV tasters rate such vegetables as significantly more bitter than AVI/AVI nontasters, whereas PAV/AVI heterozygous genotypes are intermediate in their perception of bitterness.

We hasten to add, however, that the low level of glycosinolates in broccoli and other cultivated vegetables is nontoxic, so you should still eat your vegetables! But if you find broccoli and its relatives somewhat bitter, you may well be a taster.