In multicellular organisms, we can distinguish between two broad categories of mutations: somatic mutations and germ-line mutations. Somatic mutations arise in somatic tissues, which do not produce gametes (Figure 13.1). When a somatic cell with a mutation divides (by mitosis), the mutation is passed on to the daughter cells, leading to a population of genetically identical cells (a clone). The earlier in development that a somatic mutation takes place, the larger the clone of cells will be that contain the mutation.

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Because of the huge number of cells present in a typical eukaryotic organism, somatic mutations are numerous. For example, there are about 10¹⁴ cells in the human body. Typically, a mutation arises once in every million cell divisions, so hundreds of millions of somatic mutations must arise in each person. Many somatic mutations have no obvious effect on the phenotype of the organism because the function of the mutant cell is replaced by that of normal cells, or the mutant cell dies and is replaced by normal cells. However, cells with a somatic mutation that stimulates cell division can increase in number and spread; this type of mutation can give rise to cells with a selective advantage and is the basis for many cancers (see Chapter 16).

Germ-line mutations arise in cells that ultimately produce gametes. A germ-line mutation can be passed to future generations, producing individuals that carry the mutation in all their somatic and germ-line cells (see Figure 13.1). When we speak of mutations in multicellular organisms, we’re usually talking about germ-line mutations.

Historically, mutations have been partitioned into those that affect a single gene, called gene mutations, and those that affect the number or structure of chromosomes, called chromosome mutations. This distinction arose because chromosome mutations could be observed directly, by looking at chromosomes with a microscope, whereas gene mutations could be detected only by observing their phenotypic effects. Now, with the development of DNA sequencing, gene mutations and chromosome mutations are distinguished somewhat arbitrarily on the basis of the size of the DNA lesion. Nevertheless, it is practical to use chromosome mutation for a large-scale genetic alteration that affects chromosome structure or the number of chromosomes and to use gene mutation for a relatively small DNA lesion that affects a single gene. This chapter focuses on gene mutations; chromosome mutations were discussed in Chapter 6.