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Abstract

Mutations are a natural consequence of
the interactions of our genome with genotoxic agents
and imperfections in the DNA replication machinery.
Every cell is at risk of mutations and therefore
the probability of acquiring mutations is increasing
with population size. However, the impact of a mutation
depends on the type of cell where it occurs and
the average lifetime of that cell. Tissue architecture
is organized in such a way that many mutations will
have no consequence, although the cell harboring them
may expand into a detectable clone. We will use the
known architecture and dynamics of hematopoiesis to
describe the evolution of mutant clones in age structured
populations and show why the appearance of well
recognized mutations is inevitable even if usually of no
consequence. Most mutant populations merely cause
transient ripples in a tissue. However, whenever mutations
occur in stem cells or other primitive cells, the
associated clones can have long lasting consequences
and may lead to disease.