5.9–5.11: Damage to the genetic code has a variety of causes and effects.

Damage to the genetic code can interfere with normal development.

Through the two-step process of transcription and translation, an organism converts the information held in its genes into the proteins necessary for life. But the process is only as good as the organism’s underlying genetic information. Sometimes, something occurs to alter the sequence of bases in an organism’s DNA. Such an alteration is called a mutation, and it can lead to changes in the structure and function of the proteins produced. Mutations can have a range of effects. Sometimes they result in a serious, even deadly, problem for an organism. Sometimes they have little or no detrimental effect. And occasionally—but very rarely—they may even turn out to be beneficial to the organism.

As an example of how mutations can affect organisms, consider the case of breast cancer in humans. When two human genes, called BRCA1 and BRCA2, are functioning properly, they help to prevent breast cancer by helping to repair DNA damage, preventing cells from accumulating the changes that lead to cancer. If the DNA sequence of either of these genes is altered through mutation and the gene’s normal function is lost, the person carrying the gene has a significantly increased risk of developing breast cancer. (Because a variety of other factors, including environmental variables, are involved in development of cancer, it’s impossible to know for certain whether these individuals will develop breast cancer.) Currently, more than 200 different mutations in the DNA sequences of these genes have been detected, each of which results in an increased risk of developing breast cancer.

Given the havoc they can cause for an organism, it’s not surprising that mutations have a bad reputation. After all, because they can change the protein produced, they can disrupt normal processes and harm the individual (FIGURE 5-20). But there are a couple of reasons why mutations’ bad reputation may not be fully deserved. First, it turns out that many—perhaps even most—mutations are neutral, having neither a positive nor a negative effect on an organism’s phenotype. This may be the case when a mutation occurs in a non-coding region of DNA, or when a change in DNA within a gene doesn’t alter the function of the protein produced. Based on a recent study, researchers estimate that the rate of mutations in cells involved in reproduction is approximately 10^–8 per base pair per generation.

Figure 5.20: Wreaking havoc.

A second reason that mutations’ bad reputation may be undeserved is the paradoxical fact that mutations are essential to evolution. Those mutations that don’t kill an organism, or reduce its ability to survive and reproduce, can be beneficial. Every genetic feature in every organism was, initially, the result of a mutation. (In Chapter 8, we explore the relationship between mutation and evolution.) Ultimately, most mutations you inherit from your parents will have no effect. And all of you are carrying mutations that you will never know about!

It’s important to note that mutations can occur in an organism’s gamete-producing cells (that is, cells that produce sperm or eggs) as well as in its non-sex cells (such as skin cells or cells in the lungs). Mutations in non-sex cells can have bad health consequences for the person carrying them. Many forms of cancer, such as lung cancer and skin cancer, result from such mutations. On the upside, non-sex-cell mutations are not passed on to your children.

Mutations in the sex cells (gametes), on the other hand, do not have any adverse health effects on the person carrying them, but these mutations can be passed on to offspring. Individuals inheriting certain mutations from a parent—because the mutation occurred in the parent’s sex cells, or the parent inherited the mutation from his or her parent—can be at increased risk for certain diseases such as breast cancer or cardiovascular disease. Inherited mutations can also have an effect before birth, sometimes causing miscarriages or the occurrence of birth defects.

In terms of how they physically affect DNA, mutations generally fall into two types: point mutations and chromosomal aberrations (FIGURE 5-21). In point mutations, one base pair is changed. In chromosomal aberrations, entire sections of a chromosome are altered.

Figure 5.21: Point mutations and chromosomal aberrations.

Point mutations occur when one base pair in the DNA is substituted for another, or when a base pair is inserted or deleted. Insertions and deletions can be much more harmful than substitutions, because the amino acid sequence of a protein is affected. If a single base is added or removed, the three-base groupings in an mRNA get thrown off, and the entire sequence of amino acids stipulated “downstream” from that point will be wrong—the reading frame is shifted. It’s almost like putting your hands on a computer keyboard, but offset by one key to the left or right, and then typing what should be a normal sentence. It comes out as gibberish.

Chromosomal aberrations are changes to the overall organization of the genes on a chromosome. Chromosomal aberrations are like the manipulation of large chunks of text when you are editing a term paper. The aberrations can involve the complete deletion of an entire section of DNA, the relocation of a gene from one part of a chromosome to elsewhere on the same chromosome or even to a different chromosome, or the duplication of a gene, with the new copy inserted elsewhere on the chromosome or on a different chromosome. Whatever the type of aberration, a gene’s expression—the production of the protein that its sequence codes for—can be altered, as well as the expression of the genes around it.

Given the potentially hazardous health consequences of mutations, it is advisable to minimize their occurrence. Can this be done? Yes and no. There are three chief causes of mutation and, although one of them is beyond our control, the risk of occurrence of the other two can be significantly reduced (FIGURE 5-22).

Figure 5.22: Gambling with mutation-inducing activities. You can increase or decrease your risk of mutations with your behavior: smoking, tanning, and radiation (but notice the protective lead apron).

1. Spontaneous mutations. Some mutations arise by accident as long strands of DNA are duplicating themselves—at the rate of more than a thousand bases a minute in humans—when cells are dividing (you’ll read more details on this process in Chapter 6). Most errors are corrected by DNA repair enzymes, but some slip through and there’s not much we can do about them.

2. Radiation-induced mutations. Ionizing radiation, such as X rays, is radiation with enough energy to disrupt atomic structure—even break apart chromosomes—by removing tightly bound electrons. Because ionizing rays cannot pass through lead, the lead apron a doctor or dentist puts over you when you get an X ray protects your body from the ionizing radiation. However, even non-ionizing lower-energy radiation (which is not able to remove electrons) can damage DNA. Ultraviolet (UV) rays from the sun, for example, can be absorbed by certain bases in DNA and cause them to rearrange bonds. This can prevent them from pairing correctly with the complementary DNA strand and can transform a cell into a cancer cell. This is why long-term sun exposure can contribute to the development of skin cancer.

Another source of dangerous radiation is found in the core of nuclear power plants, where radioactive atoms are used and produced in energy-generating reactions. The high energy of the radioactivity that fuels the production of usable energy can pass through your body and disrupt your DNA, causing point mutations and chromosomal aberrations. With the proper safety precautions, however, nuclear power plant workers can minimize their exposure to harmful radiation.

3. Chemical-induced mutations. Many chemicals, such as those found in cigarette smoke and in the exhaust from internal combustion engines, can also react with the atoms in DNA molecules and induce mutations.

In Section 5.11, we examine how even tiny changes in the sequence of bases in DNA can lead to errors in protein production and profound health problems.