Every single human trait—blue eyes, red hair, cystic fibrosis, a second toe longer than the big toe, and so on—is the result of some genetic mutation somewhere back down the line. Traits that are shared by all people must have arisen long ago, while other traits occur only in certain populations of people. Traits may be as innocuous as eye color or hair texture or as grave as a shared tendency toward a particular disease. Cystic fibrosis, for instance, is most common in people of northern European descent, while sickle cell anemia (see Amino Acids) occurs frequently in those of African and Mediterranean ancestry. A fatal disorder known as Tay-Sachs is found primarily in Jewish people whose ancestors came from Eastern Europe. In many cases, the particular mutation, while harmful in one regard, proved to be a useful one for that population. We know, for example, that while two copies of the mutant sickle cell anemia gene cause illness, one copy confers resistance to malaria—a very useful trait to people living in the tropics, where malaria is common.
Researchers have noted a high incidence of obesity among the Pima, a Native American tribe whose ancestral homeland is along the Gila and Salt rivers in Arizona. The Pima tend to eat a diet that is no more fatty than that of the average American—which, of course, means that it is plenty fatty, complete with chips, bologna, ice cream, and all the other high-calorie, low-nutrient foods that most Americans consume. But whereas the average American is over-weight, the average Pima is more dramatically so. This suggests that long ago, when the ancestors of the Pima had to face repeated periods of famine in the dry lands of the American Southwest, survival favored the individual or individuals who had a mutation for fat storage. It so happens that today, there is more than enough food at the local supermarket, but by now the Pima as a group has the fat-storage gene. Therefore, many members of the tribe have to undergo strict dietary and exercise regimens so as not to become grossly overweight and susceptible to heart disease and other ailments.
As with other mutations relating to ethnic groups, scientists have hypothesized that some advantage must be conferred upon people with single copies of the cystic fibrosis gene or the Tay-Sachs disease gene. Though many mutations are harmful, others prove to be beneficial to a species by helping it adapt to a particular environmental influence. Useful mutations, in fact, are the driving force behind evolution.
The processes of evolution are usually much too slow for people to discern, but it is possible to
The majority of mutations, however, are less than favorable, and this is illustrated by the relationship between mutation and certain hereditary diseases. An example is Huntington disease, a condition that strikes people in their forties or fifties and slowly disables their nervous systems. It produces shaking and a range of other symptoms, including depression, irritability, and apathy, and is usually fatal. The gene associated with Huntington's is dominant.
The horrible degenerative brain condition known as Creutzfeldt-Jakob disease, discussed in Diseases, is usually caused by another mutation. (Though it can be caused by infection, most cases of the disease are the result of heredity.) As with some of the other conditions we have mentioned, this one seems to affect particular groups more than others. Whereas the worldwide incidence of this rare condition is about one in one million, among Libyan Jews the rate is higher. The disease is a type of spongiform encephalopathy, so named because it produces characteristic spongelike patterns on the surface of the brain. Spongiform encephalopathies are caused by the appearance of a prion, a deviant form of protein whose production typically is caused by a mutation.
Most hereditary diseases are, by definition, linked with a mutation. Such is the case with hemophilia, for instance (see Noninfectious Diseases), and with cystic fibrosis, a lethal disorder that clogs the lungs with mucus and typically kills the patient before the age of 30 years. Cystic fibrosis, like Huntington, occurs when a person inherits two copies of a mutated gene. In 1989 researchers found the source of cystic fibrosis on chromosome 7, where an infinitesimal change in the DNA sequence leads to the production of an aberrant protein.
In the past, all manner of superstitions arose to explain why a child was born, for instance, with a cleft palate, a situation in which the two sides of the roof of the mouth fail to meet, causing a speech disorder that may be mild or severe. Once known as a harelip, the cleft palate was said to have formed as a result of the mother's being frightened by a hare while she was carrying the child. In fact, it is just one example of a congenital disorder, an abnormality of structure or function or a disease that is present at birth. Congenital disorders, which also are called birth defects, may be the result of several different factors, mutation being one of the most significant. Among the many examples of congenital disorder are the hereditary diseases we have already mentioned, as well as dwarfism, Down syndrome,
The term dwarf has many associations from fairy tales—an example of the combined fascination and revulsion with which people with congenital disorders have long been treated—but it also is used to describe persons of abnormally short stature. A dwarf is distinguished from a midget in a number of ways, all of which indicate that the features of a midget are less removed from the norm. Midgets, while small, have bodies with proportions in the ordinary range. Likewise, the intelligence and sexual development of an adult midget are similar to those of other adults, and a midget or midget couple typically produces children of ordinary size. Pygmies, a group of people in southern Africa, appear to be midgets through a germinal mutation, but in many populations the mutation is somatic, occurring only occasionally in families whose other members are of ordinary size.
Dwarfs, by contrast, have several different disorders. One variety of dwarfism, known in the past as cretinism, is characterized by a small, abnormally proportioned body and an impaired mind. On the other hand, several forms of hereditary dwarfism carry with them no ill effect on the mental capacity. For example, people with the type of dwarfism known as achondroplasia have short limbs and unusually large heads, but the life span and intelligence of someone with this condition are quite normal. In the case of diastrophic dwarfism, the brain is fine, but the skeleton is deformed, and the risk of death from respiratory failure is high in infancy. Persons with diastrophic dwarfism who survive early childhood, however, are likely to enjoy a normal life span.
Like people with many other congenital disorders, those with Down syndrome used to be called by a name that now is considered crude and insensitive: mongoloid. The term, when used with a capital M, refers to people of east Asian descent and is analogous to other broad racial groupings: Caucasoid, Negroid, and Australoid. In the case of people with Down syndrome, mongoloid referred to the unusual facial features that mark someone with that condition.
A person with Down syndrome (caused by an extra chromosome in the 21st chromosomal pair) is likely to have a wide, flat face and eyes that are slanted, sometimes with what is known
Compared with dwarfism or Down syndrome, albinism is not nearly as severe in terms of its effect on a person's functioning. A condition that results from an inherited defect in melanin metabolism (melanin is responsible for the coloring of skin), albinism is marked by an absence of pigment from the hair, skin, and eyes. The hair of an albino tends to be whitish blond, the skin an extremely pale white, and the eyes pinkish. Albinism occurs among other animals: hence the white rats, rabbits, and mice almost everyone has seen. Domestic white chickens, geese, and horses are partial albinos that retain pigment in their eyes, legs, and feet. As was once true of people with other congenital disorders, human albinos once inspired fear and awe. Sometimes they were killed at birth, and in the mid-nineteenth century, albinos were exhibited in carnival sideshows. In these cruel spectacles, sometimes whole families were put on display, touted as a unique race of "night people" who lived underground and came out only when the light was dim enough not to hurt their eyes.
On the other hand, some ethnic groups experience enough albino births that another one causes no excitement. For example, among the San Blas Indians of Panama, one in approximately 130 births is an albino, compared with one in 17,000 for humans as a whole. Albinism comes about when melanocytes (melanin-producing cells) fail to produce melanin. In tyrosinase-negative albinism, the most common form, the enzyme tyrosinase (a catalyst in the conversion of tyrosine to melanin) is missing from the melanocytes. When the enzyme is missing, nomelanin is produced. In tyrosinase-positivealbinism, a defect in the body's tyrosine transportsystem impairs melanin production. One inevery 34,000 persons in the United States has tyrosinase-negative albinism. It is equally common among blacks and whites, while more blacksthan whites are affected by tyrosinase-positivealbinism. Native Americans have a particularlyhigh incidence of both forms of albinism.
As might be expected, cells that divide many, many times in a lifetime are more at risk of errors and mutations than cells that divide less frequently. In a human female, egg cells are fully formed at birth, and they never divide thereafter. By contrast, sperm cells are being produced constantly, and the older a man is, the more frequently his sperm-producing cells have divided. By age 20 they will have divided 200 times and by age 45 about 770 times. This has led scientists to hypothesize that when a baby is born with a congenital disorder caused by an error in cell division, the father is the parent more likely to have contributed the gene with the mutation.
This is just one example of why mutation occurs. Many mutations are caused by mutagens—chemical or physical factors that increase the rate of mutation. Some mutagens occur naturally, and some are synthetic. Cosmic rays from space, for instance, are natural, but they are mutagenic. Some naturally occurring viruses are considered mutagenic, since they can insert themselves into host DNA. Hydrogen and atomic bombs are man-made, and they emit harmful radiation, which is a mutagen. Recreational drugs, tobacco, and alcohol also can be mutagens in the bodies of pregnant women. The first mutagens to be identified were carcinogens, or cancer-causing substances. Carcinogens in chimney soot were linked with the chimney sweep's cancer of late eighteenth-century England, discussed in Noninfectious Diseases. In fact, cancer itself is a kind of mutation, involving uncontrolled cell growth. Other environmental factors that are known to bring about mutations include exposure to pesticides, asbestos, and some food additives, many of which have been banned.
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