Home > Encyclopedia of Food & Culture > Genetics

GENETICS. Since the first efforts were made to cultivate plants, humans have employed genetics to breed crops with improved taste, hardiness, or yield. The long history of genetics and nutrition can be felt even today, and permeates many aspects of our daily life. Home gardeners can purchase seeds that will grow in particular soils, produce fruit at various times of the year, or grow in sunshine or shade. Local supermarkets sell supersweet varieties of corn and fruits such as the tangelo, made from crossing grapefruits with tangerines. The "Green Revolution," which began with the identification of a high-yield strain of wheat, has resulted in dramatic increases in food production around the world. With the advent of genetic engineering, new, disease resistant crops have been developed, with the promise of reducing requirements for pesticide use.

Plants are not the only organism to be subjected to genetic breeding programs by humans. Yeast strains for baking bread or producing alcoholic beverages have been cultured for centuries. Meatier turkeys and cows that give more milk are the product of animal breeding efforts. Some have argued that the genetic manipulation of foodstuffs has gone too far, emphasizing crops that can withstand long storage times, transportation to markets, and handling by the consumer over any selection for flavor. Others worry that genetic engineering gives us unprecedented, and perhaps dangerous, opportunities to mix and match desired traits. It is nevertheless apparent that genetics has had an enormous impact upon society.

What is genetics? Simply put, genetics is the study of hereditary variation. This variation, in essence, is the diversity of life as it exists in all its forms on earth. For example, there are perhaps some 300,000 different species of flowering plants. What makes each of these plants different from one another? Perhaps even more amazing than this variation between species, there are astounding levels of variation that can be found even within a species. There are, for example, some 6,000 different varieties of apples alone. Genetics aims to understand how this variation occurs between species as well as within species. The term "phenotype" is used to describe any differences that can be observed or measured. For example, the possession of yellow kernels is a phenotype of a particular strain of corn, which distinguishes it from strains that possess white kernels. The two may have phenotypes in common (e.g., they both have white flowers or are supersweet) in addition to the differing phenotype of yellow and white kernels. Genetics examines the ground rules regarding how these phenotypes are passed on, or inherited, from one generation to the next.

Gregor Mendel, the Father of Genetics

While genetic breeding has been practiced for many hundreds of years, the true science of genetics began with Gregor Mendel, an Austrian monk who published his seminal work in the mid-1800s. At the time, genes had not been identified; indeed, the term itself would not be coined until 1909. How traits could be inherited from one generation to another was entirely unclear. Charles Darwin himself proposed the pangenesis theory, in which traits from the parents are passed to their children in a process that "blends" them together. In this theory, children represent a melding of the two parental sets of traits. They in turn would pass their traits on to their children, further blending together the traits of their respective parents. This model of how genetics operates can be contrasted with the particulate theory, in which traits are retained on small particles passed from one generation to the next. While Darwin's model would seem to be consistent with what we can observe in our own children, Mendel's carefully performed and insightful experiments clearly supported the particulate theory, and laid down the basic principles of the inheritance of phenotypes.

Mendel discovered his principles working with pea plants, which were raised not only for their experimental value but also as a food source for the monastery. Mendel's seminal idea was to identify clearly defined and distinct traits among these plants, and determine how these phenotypes were passed from one generation to the next. For example, Mendel identified plants that possessed either white flowers or purple flowers, but not both. He then crossed these two different variants with one another (the "parental," or P0 generation), and examined the flower color of the resulting progeny plants in the filial, or F1, generation. If the blending theory were correct, one might expect pink flowers to be produced in the F1 plants. Instead, Mendel obtained only purple flowered plants. If these F1 purple-flowered plants were then interbred with one another, producing an F2 generation of plants, Mendel saw once again pea plants with white flowers. Thus, even though this particular trait (white flowers) had not been seen at all in the F1 generation, it had been retained, and could be recovered in the F2 generation. These results clearly supported the particulate theory.

To obtain his results, Mendel studied the transmission of seven distinct phenotypes among some 28,000 pea plants, and synthesized them into a mathematical model of genetic inheritance. In doing so, he did what had never been done before; he quantified his results. From an analysis of his data, he was able to infer several key principles. He argued that there must exist determinants that specify particular phenotypes, a feature we now recognize as genes. He also argued that these determinants are located on particles, one of which is donated by the father, and one by the mother. These particles, now known to be chromosomes, produce a progeny plant that has one determinant for flower color donated by the mother, and one determinant for flower color donated by the father. The phenotype of the progeny plant will depend upon the particular combination of determinants it receives from its parents. Mendel deduced that the determinant for the production of purple flowers (represented as "P") is dominant over the determinant to produce white flowers (represented as "p"). Conversely, the white flower determinant is recessive in the presence of the purple-flower determinant. Two copies of the purple-determinant (P/P) in a plant, one maternal and one paternal, results in purple flowers. One purple and one white flower determinant (P/p) still produces purple flowers. Only if a plant receives two white flower determinants (p/p) will it possess white flowers.

Mendel's results were not widely known at the time. Some thirty-five years later, his work was "rediscovered" by geneticists who had repeated his results in other organisms. The implications of Mendel's work were revolutionary. For the first time, it was possible to observe the patterns of inherited phenotypes of a plant, animal, insect, or bacterium, and deduce, with mathematical precision, the expected genotypes of these organisms. It is a tribute to the work of Mendel and others of his time that their results were obtained despite not knowing that genes were encoded by DNA or how genes act to produce the observed phenotype.

Single Gene Effects

Part of Mendel's success was due to his implicit recognition that there are two primary types of variation: discontinous and continuous. In discontinuous variation, a particular phenotype can be found in a population in at least two distinct forms. For example, Mendel's peas possessed purple or white flowers, and not both. On the other hand, in continuous variation, a range of similar phenotypes can be observed in the population. An example of this among humans might be the observation that noses come in all shapes and sizes. In most instances, genetics has focused predominantly upon discontinuous variants, as the associated phenotypes can be clearly recognized and categorized. As it turns out, many of the phenotypes that fall into this group can be associated with alterations in the function of a single gene. In our purple versus white flower example, the gene that is normally responsible for giving the plant its purple color has been mutated, such that it no longer functions. In the absence of this gene, white, or uncolored, flowers are produced. The different forms of this same gene (P, indicating normal or wild-type function, and p, indicating altered or mutant function) are called alleles. If an allele is widely represented in the population, as is the case among white or purple flowers in pea plants, they are termed polymorphisms.

Polymorphisms can be identified in other organisms as well. However, in humans, there are also additional issues of ethnicity and race. A common polymorphism among Asians, for example, is a particular allele of the alcohol dehydrogenase 2 (Adh2) gene. This allele negatively affects the enzyme's ability to metabolize alcohol, and is possessed by more than 90 percent of the Japanese population. In the European population, on the other hand, less than 10 percent have this allele. Similarly, lactose intolerance is due to allelic variation in the lactase gene. An allele that leads to low activity of lactase following early childhood is common in Africans and Asians (>80 percent), and rarer in Caucasians (17–50 percent). These relatively common polymorphisms are just a few of the many thousands of alleles known to exist in humans.

Why these polymorphisms exist is not clear, although it can be hypothesized that they either do no harm to individuals who harbor these particular alleles, or, if they are in fact somewhat harmful, are nonetheless still of some benefit. This can be described as the fitness of the allele. For example, as many as 10–20 percent of the European population bears a polymorphism in the gene encoding methylenetetrahydrofolate reductase (MTHFR). These individuals have a greater risk of neural tube defects, such as spina bifida, due to the fact that this allele affects folate metabolism. Why then, is such a polymorphism maintained in such a high percentage of the population? The answer may lie in the observation that individuals with this polymorphism have an increased efficiency of blood clotting. As mortality resulting from bleeding after childbirth was a common occurrence, this would be beneficial to individuals bearing this polymorphism. While it is often dangerous to speculate why a polymorphism exists, if this reduction in risk is substantiated, it would obviously be of benefit both to the individual and the population as a whole.

While we have centered this discussion around polymorphisms, on occasion, an allele will arise that affects only a small percentage of the population. Although these rare variants are uncommon (<1 percent of the population), they make up a large proportion of the patients that are hospitalized for medically related conditions. One such example would be phenylketonuria, which occurs in one out of every 10,000 births. This medical condition is due to a mutation in the phenylalanine hydroxylase gene, and leads to a failure to metabolize phenylalanine containing compounds, such as aspartame. If unrecognized, infants with PKU invariably develop mental retardation. This can be avoided by monitoring dietary intake to eliminate phenylalanine-containing compounds. How is PKU inherited from one generation to another? The fields of medical genetics and genetic counseling encompass the analysis of family histories, so as to better treat individuals who are at risk from these illnesses. If we examine the family history of a typical patient that has PKU, we might observe the following:

In this case, neither parent in the P0 generation suffers from the disease, but some of their children do. Applying principles learned from Mendel's work, we can infer the genotype of the family members from this phenotypic analysis:

From the study of this family history, it is clear that PKU is inherited in a recessive manner. Adults who are heterozygous for mutations in the phenylalanine hydroxylase gene (K/k; possessing one wild-type or normal allele and one mutant allele) do not have PKU. Only those with two mutant copies (k/k) display the condition. Thus, Mendel's laws apply equally well to humans as they do to peas. Interestingly, however, while the phenotype of PKU patients indicates a recessive inheritance of this condition, an analysis of the genotype of these patients and the population in general reveals the existence of more than 400 alleles of the phenylalanine hydroxylase gene. This astounding degree of allelic heterogeneity indicates that most PKU patients indeed possess two mutant alleles of the hydroxylase gene, but that these two alleles are likely to be completely different. The phenotypic effect is the same; elimination or severe alteration of the normal function of the gene leads to PKU. The molecular basis of this defect, however, is dependent upon the specific alleles that are involved. It is plain to see that the field of molecular genetics, which examines the actual genes responsible for these defects, is an important complement to more traditional genetic phenotypic observations.

While the examples we have looked at so far have comprised diseases or phenotypic traits that are inherited in a recessive fashion, many diseases are inherited in a dominant manner. In these instances, a single copy of the mutant allele is sufficient to confer, at least partially, a medically associated condition. An example of this might be familial hypercholesterolemia, which is associated with an inability to properly metabolize cholesterol. A family history of patients with this affliction might appear thus:

Compare the rate of occurrence of this condition with that of PKU. Only a single copy of the mutant allele is required to produce at least some phenotype in cases of familial cholesterolemia. In many of these dominantly inherited diseases, individuals that possess two mutant alleles are much more strongly affected than individuals with one mutant and one wild-type allele. In familial hypercholesterolemia, homozygous patients (those with two mutant alleles; H/H) rarely live past the age of 30. These individuals are rare, however, occurring in perhaps one in one million. Heterozygous individuals (those with one mutant and one wild-type allele; H/h), on the other hand, are extremely common, and are present in perhaps one in 500. These individuals have a higher propensity for premature heart disease due to the buildup of atherosclerotic plaques, but without the severity of phenotype exhibited by homozygous individuals.

These examples illustrate just a few of the more than 1400 single-gene disorders that have been identified. It has been estimated that in any one individual, perhaps 20 percent of all genetic loci are heterozygous. This suggests that a striking degree of individuality exists at the genetic level. This allelic variation may explain, for example, the differential response of individuals to environmental, dietary, or pharmacological effects.

Multiple Gene Interactions

So far, we have discussed examples of phenotypes that can be traced to alterations of a single gene. While great strides have been made in identifying genes that are associated with a particular phenotype, it is clear that we are far from understanding how genes interact with one another as a whole. For example, many genetic disorders are thought to result from the interplay of multiple genes with epigenetic, or environmental, influences, such as diet. One means of trying to understand these multifactorial disorders and how genes and the environment interact is to examine at a molecular level how genes function. While Mendel derived his results from observing the phenotype of his plants, a molecular geneticist might ask, what is the actual gene that is responsible for production of purple pigment? What is its sequence? How does it function in the plant cell to produce color? With what other genes does it interact?

DNA has often been called the "blueprint of life," and indeed, DNA is the thread that ties almost all life on earth together. Rules that govern the replication of DNA and its transmission to daughter cells (e.g., during cell division) are the same in nearly all organisms. But if DNA is DNA whether or not it is found within a fly or a human, how is it possible to obtain such diverse organisms? The answer, of course, is that the genes that exist within DNA are different from flies to humans. One might suspect that these two diverse organisms would possess radically different sets of genes, separated as they are by over 600 million years of evolution. With the advent of the Human Genome Project, it has become possible to directly test this hypothesis. Once the entire sequence of human DNA was known, it was compared to the sequence of Drosophila melanogaster, a fruitfly that has been used for over one hundred years as a genetic model. This comparison revealed an astonishing 40 percent of all genes in the human have similar counterparts in the fruit fly. While this figure is still tentative, and gene number is hardly an adequate means of comparing differences among species, it underscores yet again that genetic principles learned in model organisms, such as the fruit fly, can have important theoretical and practical applications in understanding human genetics.

If variation between species is accomplished, at least in part, by genes that are unique to flies or humans, how does variation occur within a species? All cells in the human body, with the exception of those involved in the production of sperm or ovum, contain identical DNA sequences, and therefore identical sets of genes. How is it then, that a skin cell will develop differently from a hair cell, if both contain the same DNA? The answer is that each cell may contain the same genes, but not all the genes will be expressed in each cell. Current estimates suggest that there are approximately 50,000 genes in the human genome. Any given cell type, however, is thought to express some 15,000 of these genes. Thus, a hair cell will express 15,000 genes, but these genes will be somewhat different from the 15,000 that are expressed by a skin cell. It is this differential gene expression that leads to the differences in observed phenotype between the two cell types. In a similar vein, two noses located on the faces of two different individuals may well be specified by the same 15,000 genes, but slight differences in their expression from one individual to the next may well explain the somewhat petite nose on one and the rather large proboscis on the other. The growing field of genomics aims to study, at a global level, the interactions of all of the genes that contribute toward a particular phenotype.

If it does indeed require 15,000 genes to produce any given cell in the body, then mutant alleles that arise in any one of these genes may, or may not, strongly affect the development of that cell. Alleles of certain genes may alter the color of the cell, or perhaps its ability to metabolize phenylalanine-containing products. Or it is possible that an alteration in just one gene among 15,000 may have no discernable effect at all. How these thousands of genes interact with one another to produce a given trait is perhaps the biggest challenge that faces the molecular geneticist studying genomics today. Moreover, these genetic interactions are often complicated by epigenetic influences as well. Nutrition, in particular, has very strong effects on gene expression. Many multifactorial diseases, such as diabetes, are thought to be associated with both genetic and environmental risk factors. A given family history may, to the medical geneticist, indicate a predisposition towards diabetes, but other factors, such as diet and exercise, are also thought to influence the development of this disease.

One particularly fascinating example of the link between nutrition and genetics is the effect of diet upon aging. Unusual longevity in humans has often been attributed by these self-same individuals as directly associated with the manner in which they have lived their life. Whether it is a glass of wine each day, eliminating red meat, or ingesting large quantities of vitamin C, these individuals claim to have identified the reason behind their advanced years. How much can truly be attributed to these epigenetic influences, and how much is based upon the individual's particular genetic makeup? Research in model organisms such as the fruit fly has identified a handful of genes that seem to strongly affect the lifespan of the fly. Mutations in the methuselah gene, for example, allows flies to survive more than 35 percent longer than their normal lifespan. This astonishing result suggests that aging may actually be strongly influenced by a limited number of genes, many of which are involved in metabolism. On the other hand, it has long been known that reducing the calorie intake of rodents by 40 percent can also markedly increase their lifespan. The new field of genomics has begun trying to identify the molecular basis for this increase in longevity, by comparing how many genes are differentially expressed between calorie-restricted rodents and their non-restricted counterparts. It was found that hundreds of genes had been affected, including a large number known to be involved in metabolic processes. Thus, the effects of nutrition on aging can be profound. How much of this is due to our genes? How much can attributed to single genes? How much is due to our caloric intake? The answer to this "age-old" question remains to be determined.

A similarly tantalizing example demonstrating the link between nutrition and genetics lies in the area of control of bodyweight. Mice that are homozygous mutant for a particular allele of the obese gene (ob/ob) are grossly overweight. The excitement that surrounded this result centered around the possibility that weight gain might be strongly influenced by individual genes, and that no amount of dietary control or exercise can alleviate its effects. This, of course, has been shown to be a gross oversimplification, and it is clear that many genes are involved in the regulation of body weight. Nevertheless, it is apparent that the field of genetics is gradually beginning to unravel some of the major problems in nutrition and biology today.

Conclusions

The practice of genetics is as old as the human race, and yet as a science, it is still in its infancy. The study of genetics stretches across all of biology, and has grown to include many sub-specialties within the field. Cytogenetics, for example, is the study of chromosomal defects, such as trisomy 21. Molecular genetics is the analysis of individual genes, such as Adh2, and their function within the cell. Population genetics studies the frequency with which polymorphisms of Adh2 occur within large subsets of individual organisms. Medical genetics searches to identify patterns of inheritance of diseases within patients, and the effect of epigenetic influences such as diet and exercise. And finally, genomics tries to understand how genes behave as a whole to specify particular cell types or phenotypes. Together, these diverse but inter-related fields aim to understand how variation is established and maintained within biology.

See also Agriculture since the Industrial Revolution; Crop Improvement; Gene Expression, Nutrient Regulation of; Genetic Engineering.

David Ming Lin