4.1The Relationship between Genes and the Environment
Similarities and Differences between Parents and Offspring
Fig. 4-1 Interactions between Genes and the Environment
Organisms live through interactions between various genes and environmental factors.
There are various types of organisms on the earth, and each has a characteristic form. There are also over six billion people on the earth, yet no two people have the same face. Nevertheless, parents and children somehow appear similar. Notably, identical twins, who are born from the same zygote, have the same genes, and have very similar phenotypical characteristics. Therefore, the questions of what is/is not determined by genes have led to an increased emphasis on research on identical twins.
As described in Chapter 3, the inheritance of phenotypes determined by a single gene is called "Mendelian inheritance," and this mode of inheritance has been well studied. In reality, however, inheritance often is not Mendelian, but involves multiple genes. For example, identical twins have similar phenotypical characteristics, yet they somewhat differ in their susceptibility to diseases.
Identical twins often mutually exhibit the same symptoms for childhood cancer and congenital metabolic abnormalities, which are determined by a single gene. The general frequency of schizophrenia is about 1%, but if one of a pair of identical twins develops the disease, the other twin has a 40% chance of contracting it sometime in his or her lifetime. It has been reported, however, that the rate of adult cancer in pairs of identical twins is as low as 20%. In other words, the higher the probability that a disease will occur in both twins, the more closely involved is the genetic predisposition factor for that disease.
Even when both the identical twins have the same genetic predispositions, their phenotypes often differ because of differences in environment. Environmental and nutritional conditions have changed greatly in Japan, for example, the average height of Japanese adult males was 155 cm during the Edo Period and 160 cm after World War II, and is presently about 170 cm. There have also been many big changes with respect to the environmental factors that cause diseases, for example, changes in eating habits and lifestyles in recent years have caused a decrease in stomach cancer and an increase in colon cancer (Fig. 4-1). Therefore, a major challenge for the life sciences is to figure out what genes determine and how they determine it.
The Relationship between Genes and Susceptibility to Diseases
Cancer, heart disease, and stroke, which are the main causes of death in Japan, involve multiple genes and environmental factors. Opinions about the causes of diseases have changed considerably based on the understanding that many factors are involved in a disease. The concept of disease susceptibility genes is now used to explain the causes of diseases.
The apolipoprotein E (apoE) gene is involved in blood cholesterol levels. Some people are known to have the unique apoE types 2, 3, and 4, which code unique amino acid sequences. Epidemiological research has shown that differences in these apoE sequences are related to the development of arteriosclerosis and dementia (see Chapter 6).
As shown in Figure 4-2, people who have inherited an apoE type2 gene from both their father and mother (indicated by "type 2/2") usually have lower blood cholesterol than healthy people. However, if type 2/2 people have abnormalities in lipid metabolism genes or consume too much cholesterol, they develop hypercholesterolemia and increase arteriosclerotic diseases. In such cases, people who have the apoE type2 gene are highly susceptible to abnormalities in cholesterol metabolism. On the other hand, people with apoE type2/2 also respond well to treatment for hypercholesterolemia. This is an example of how the knowledge of a genetic abnormality helps in effective prevention and treatment of diseases.
Fig. 4-2. Cholesterol Metabolism Abnormalities and the Disease-Susceptibility Gene ApoE
(1) People with apoE 2/2 usually have low cholesterol levels.
(2) However, when type 2/2 people have other genetic abnormalities or consume excess calories, they exhibit prominent hypercholesterolemia.
(3) Such patients respond well to drug therapy.
Sensitivity to Diseases Involving Multiple Factors
Common modern diseases such as cancer, heart disease, and stroke involve multiple factors. Mutations in the apoE gene increase susceptibility to diseases such as cholesterol abnormalities, but the presence or absence of other factors also increases cholesterol, and sometimes, decreases it. In such cases, the gene activity changes depending on the environment and other genetically predisposing factors. Multifactorial diseases, also called lifestyle diseases, cannot be understood based on only one gene. Rather, these diseases need to be understood in terms of lifestyles and regulatory mechanisms of the human body. Diseases develop due to interactions between genes and the environment.
In addition, susceptibility differs if the same genetic mutation causes dissimilar diseases in two individuals. People with ApoE 4/4 tend not to develop cholesterol abnormalities, but tend to develop Alzheimer's disease. Dementia is prone to occur at age 85 or older in ordinary people, but at about age 75 in people with apoE 4/4 genes, indicating that people with these genes are resistant to arteriosclerosis but are susceptible to Alzheimer's disease and dementia.
Traits determined by multiple factors are often talked about as if they were caused by single genes, such as genes for behavior or personality, but such ideas should be approached with caution. We should approach such a discussion with caution.