Only germ-line mutations are transmitted to progeny.

Which is more important—the rate of mutation per nucleotide per replication or the rate per genome per generation? That depends on context. Mutations can take place in any type of cell. Those that occur in eggs and sperm and the cells that give rise to them are called germ-line mutations, and those in nonreproductive cells are called somatic mutations. This distinction is important because somatic mutations affect only the individual in which they occur—they are not transmitted to future generations. In contrast, germ-line mutations are transmitted to future generations because they occur in reproductive cells.

For germ-line mutations, it is the rate of mutation per genome per generation that matters more. Germ-line mutations are important to the evolutionary process because, as they are passed from one generation of organism to the next, they may eventually come to be present in many individuals descended from the original carrier.

For somatic mutations, the mutation rate that matters is the rate of mutation per nucleotide per replication. Although somatic mutations are not transmitted to future generations, they are transmitted to daughter cells in mitotic cell divisions (Chapter 11). Hence, a somatic mutation affects not only the cell in which it occurs, but also all the cells that descend from it. The areas of different color or pattern that appear in “sectored” flowers, valued as ornamental plants (Fig. 14.3), are usually due to somatic mutations in flower-color genes. A mutation in a flower-color gene occurs in one cell, and as the cell replicates during development of the flower, all its descendants in the cell lineage—the generations of cells that originate from a single ancestral cell—carry that mutation, producing a sector with altered coloration.

image
FIG. 14.3 Somatic mutation. Somatic mutations in the Japanese morning glory (Ipomoea nil) in cell lineages that differ in their ability to make purple pigment cause sectors of different pigmentation in the flower.

294

Most cancers result from mutations in somatic cells (Chapter 11). In some cases, the mutation increases the activity of a gene that promotes cell growth and division, while in other cases, it decreases the activity of a gene that restrains cell growth and division. In either event, the mutant cell and its descendants escape from one of the normal control processes. Fortunately, a single somatic mutation is usually not sufficient to cause cancer—usually two or three or more mutations in different genes are required to derail control of normal cell division so extensively that cancer results.

To cause cancer, the mutations must occur sequentially in a single cell line. Fig. 14.4 shows three key mutations that have been implicated in the origin of invasive colon cancer: p53, Ras, and APC. Each mutation occurs randomly, but if, by chance, a mutation in the Ras gene occurs in a cell that is derived from one in which the APC gene has been mutated, that cell’s progeny forms a polyp. Another chance mutation in the same cell line, which now carries mutations in both the APC and Ras genes, could lead to malignant cancer. Normally, the occurrence of multiple mutations in a single cell lineage is rare, but in people exposed to chemicals that cause mutations or who carry mutations in DNA repair processes, multiple mutations in a single cell lineage are more likely to occur and so the risk of cancer is increased.

image
FIG. 14.4 Three somatic mutations implicated in the origin of invasive colon cancer. These mutations must occur in the same cell lineage for cancer to develop.