The Intersection of Food and Genes

The so-called “genetics revolution” promises to change many aspects of our lives, including what we eat. Discoveries in genetics make it possible to understand the effects of nutrients in processes at the molecular level in the body and also the variable effects of dietary components on each individual.

This insight creates opportunities to prevent disease and improve quality of life through functional foods and tailored diets.

Background
Life is specified by genomes. Every organism, including humans, has a genome that contains all the biological information—the complete DNA (deoxyribonucleic acid) sequence—needed to build and maintain a living example of that organism. The biological information contained in a genome is encoded in its DNA (double-stranded, twisting structure) and divided into discrete units called genes. Proteins are encoded by genes through a process called gene expression that involves conversion of the encoded information first to messenger RNA (ribonucleic acid, a single-stranded structure). The resultant proteins may then function in myriad ways, serving as enzymes (essential compounds that aid biochemical reactions), hormones, and building blocks for cells throughout the body. Simply put, gene expression governs our existence.

The genetic code is specified by “letters” representing the four nucleotide bases (chemical units comprising DNA)—A (adenine), C (cytosine), T (thymine), and G (guanine). DNA and gene sequences—and ultimately the proteins produced by those genes—vary from one person to the next because of small individual genetic variations occurring in one of these nucleotides. Known as a “single nucleotide polymorphism” (SNP, pronounced “snip”), genetic variations occur when a single nucleotide, such as an A, replaces one of the other nucleotide bases (C, G, or T). More simply, replacing one link in a chain with another, different link. These common variations are sometimes inherited. Although the differences in proteins are minor (usually on the order of one amino acid, a small protein building-block), the effects on protein function may be significant, resulting in varying individual responses to environmental factors, such as diet and drugs.

The genotype is the genetic constitution (complete set of genes) of an individual or organism. Phenotype, on the other hand, is the outward appearance or physical characteristics (e.g., hair color, weight, or the presence or absence of a disease) of an individual or organism. Phenotypic traits are not necessarily genetic.

Diet is one of the key environmental factors to which our genes are exposed, from conception throughout life. Nutrients in our diets govern the concentration of different proteins in different organs, functioning as regulators of various processes in gene expression (e.g., mRNA degradation). The amount of a food component consumed and the frequency with which it is ingested affect the intensity of the dietary signal and the subsequent response. Which genes are affected also may depend on the age of the individual.

Improved understanding of human dietary requirements results from developments in many scientific disciplines, including food science, nutrition, chemistry, biochemistry, physiology, and genetics. New geneticsbased research may help identify the biological basis by which food components promote health and wellness. Continuing and accelerating this research will reveal additional information about the effects, at the molecular level, of nutrients on processes in the body and will document the variable effects of nutrients under different conditions.

New Disciplines
Nutrigenomics, proteomics, metabolomics, and bioinformatics are new disciplines that will contribute to the rapid development of functional foods. These disciplines and their related tools have already improved our understanding of food science and human nutrition.

Nutrigenomics
Nutrigenomics is defined as the interaction of dietary components with genes, the study of which describes how dietary components affect the protein profile of an individual. The dietary components of interest can be essential nutrients (e.g., vitamins, minerals, fatty acids), other bioactive substances (e.g., phytochemicals) or metabolites of food components (e.g., retinoic acid, eicosanoids). On the one hand, nutrigenomics represents a logical extension of biotechnology, molecular medicine, and pharmacogenomics; on the other hand, it represents a revolution in how nutrition and diets are viewed in relation to health.

Proteomics
Proteomics is the study of the full set of proteins encoded and expressed by a genome. Through proteomics, the alteration of protein profiles by dietary components is described and the interaction of proteins and their biologic activities are studied.

Metabolomics
Metabolomics (or metabonomics) is metabolite profiling, which describes at the cellular level the outcome of changes in protein profiles and biological systems described by genomics and proteomics. In this arena, metabolic fluxes in individual cells or cell types and their regulation are investigated. Metabonomics combines the power of high-resolution nuclear magnetic resonance spectroscopy with statistical data analysis of in vivo metabolite patterns (results of studies conducted within a living organism). This technique enables rapid screening for xenobiotic (foreign to the body) toxicity, disease state, drug efficiency, nutritional status and even gene function in the “whole” organism.

Bioinformatics
Bioinformatics is the field of science in which biology, computer science, and information technology merge to form a single discipline based on creating and mining extensive computerized databases of nucleic acid sequences, gene structures, proteins and their function, as well as environmental constituents capable of modifying gene expression. The ultimate goal of the field is to enable the discovery of new biological insights as well as to create a global perspective from which unifying principles in biology can be understood. Bioinformatics tools may be used to monitor sequential metabolic changes in response to functional food components, facilitating evaluation of the safety and efficacy of the components.

Future Developments
Although scientists knew a relationship existed between early diet and gene expression, they were unable to understand how the effect took place. Now, with the integration of genomics and nutrition, our understanding of exactly how diet affects gene expression at the molecular level is emerging. This new understanding opens the door for many potential nutritional interventions, both in food composition and in food selection.

The premise that foods consumed during the first weeks and months of life may have permanent effects on metabolism is not new. Studies in humans and animals have demonstrated permanent effects of early diet on adult metabolism, cognitive function, and body composition through activation or suppression of gene expression, or turning genes “on” or “off.” Ample scientific evidence demonstrates that diet is a significant environmental determinant, if not the key determinant, of population or individual genetic expression. The effects can be overt, such as the effects seen in vitamin deficiency diseases, or more subtle and complex, as in the manifestation of type 2 diabetes, predisposition to obesity, and other chronic diseases.

The health consequences of the interaction between an individual’s diet and his or her genetic makeup have been repeatedly demonstrated. In fact, some life-threatening errors of metabolism have been successfully managed with diet modification. For example, galactosemia, a genetic disorder characterized by an inability to convert the sugar galactose to glucose, is usually discovered in infants fed milk shortly after birth because milk contains a large quantity of galactose. If not treated, galactosemia can result in cataracts, enlarged liver and spleen, and mental retardation. It is treated by lifelong elimination of milk and other dairy products from the diet. Another example of an inborn error of metabolism, phenylketonuria (PKU) is caused by an enzyme defect in the liver that breaks down phenylalanine. As a result, phenylalanine builds up in the body, causing mental retardation. Although PKU cannot be prevented, detected early in life it can be successfully treated by consuming a diet low in phenylalanine.

Studies designed to identify specific effects of diet on phenotypic expression of biochemical components that determine health have resulted in tantalizing suggestions for dietary interventions designed to modify gene expression. Through traditional nutritional research and epidemiological observation we know that nutrients play a number of important roles in metabolism. New genetic research techniques are finding that nutrients also regulate the genes whose expression leads to enzymes, structural elements, and other key substances that comprise the living, functioning organism.

The Human Genome Project and associated programs (the sequencing/decoding of the human genome) have provided the groundwork for scientists’ ability to pursue key questions, such as: What DNA variants underlie disease and health? How does the environment interact with genes, subjecting some individuals to difficult to control obesity, cardiovascular disease or Alzheimer’s disease at early ages, while others have a long life with little or no disease?

Genetic factors may confer susceptibility or resistance to a disease and may determine its severity or progression. Since we do not yet know all of the factors involved in the intricate disease causation or progression pathways, researchers have found it difficult to develop tests to screen for most diseases and disorders. By studying segments of DNA that have been found to contain a SNP associated with a specific disease trait, researchers may begin to find the relevant genes associated with a disease and variable response to dietary components. In fact, it is already possible to identify individuals with a SNP profile that predicts variable cardiovascular health status in response to diets with a particular fat composition.

Defining and better understanding the role of genetic factors in disease also will allow researchers to better evaluate the role that non-genetic factors—such as behavior, diet, lifestyle and physical activity—have on disease.

While the genetic variations that appear to be associated with some diseases can be identified, a substantial amount of biological research remains to be completed to unequivocally link, in a cause-effect equation, the phenotypic expression of health or disease in response to intake of a specific nutrient or bioactive component. Experimental results show that individuals whose genetic makeup contains particular SNPs may respond to dietary components in ways that result in gene expression that leads to disease phenotypes.

The challenges facing nutrigenomics are similar to those encountered in drug development. Many common diseases are not caused by a genetic variation within a single gene. Instead, such diseases are caused by complex interactions among multiple genes, in conjunction with environmental and lifestyle factors. Although both environmental and lifestyle factors contribute tremendously to disease risk, their relative contributions and effects are currently difficult to measure and evaluate.

Now that the human genome has been catalogued, the race is on to determine the functional significance of each gene, understand the complex functional networks and control mechanisms, and figure out the role that genotype and environment play in determining the phenotype of an individual. Functional studies to date have largely evaluated one gene at a time. However, to truly understand the biology of processes directed by genes, researchers need to simultaneously study functional interactions, networks, and pathways. With enough data and proper bioinformatics tools, scientists will be able to model the genetic circuitry to identify interventions that can optimize biological outcomes through health and wellness lifestyle choices such as diet


Recognizing the tremendous health benefits offered by functional foods, the Institute of Food Technologists commissioned an expert panel to review the available scientific literature related to functional food development. The panel’s report is divided into nine sections: Definitions, Introduction, Food and Genes, Current Legal Standards, Scientific Standards, Policy Limitations, Bringing Functional Foods to Market, Role of Research, and Conclusions. Copies of the report are available at www.ift.org. Founded in 1939, the Institute of Food Technologists is an international not-for-profit scientific society for food science and technology.