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STEM CELLS: POPULATION GENETICS 285

probability that the pool maintains two distinct lineages or coalesces
into one lineage after a single round of cell division. Figure 13.7 calcu-
lates the probability of lineage diversity versus coalescence through two
rounds of symmetric cell division.
Asymmetric and symmetric division have different consequences for
the evolution of stem cell compartments. With asymmetric division,
mutations remain in the stem pool but do not spread, unless those mu-
tations break the asymmetry and force competition between lineages.
With symmetric division, a mutation may be lost by chance or may take
over the entire compartment. If a mutation takes over the compartment,
any subsequent mutation in the compartment adds a second hit.

13.4 Summary

This chapter described the population genetics of somatic cell lin-
eages, with an emphasis on stem cells. The theory of population genetics
provides analytical tools to calculate how mutation, competition (selec-
tion), and random sorting of lineages (drift) influence the rate at which
mutations accumulate in cell lineages. Several recent papers have ap-
plied population genetic theory to analyze how the demography of the
stem cell compartment influences the accumulation of mutations and
the progression of cancer (e.g., Komarova et al. 2003; Michor et al. 2003;
Frank 2003c; Michor et al. 2004). The next chapter begins with empir-
ical studies of stem cell population genetics, and follows with a more
general review of cell lineage evolution and somatic mosaicism.