Figure 2.

Scaled classes of variants (depending on the size of the variant, mechanism, and timing of the event). There are numerous endogenous molecular mechanisms that generate postzygotic somatic variants causing mosaicism during the lifetime of an individual, whereas others (such as Alu and L1 retrotransposition) are likely to have specific temporal patterns1, 37. The main genomic and epigenetic mechanisms are: a) DNA damage by reactive oxygen species; b) replication error by DNA polymerase and erroneous DNA repair; c) DNA polymerase slippage and trinucleotide repeat expansion; d) both short and long interspersed nuclear element (Alu and L1) retrotransposition; e) fork stalling and template switching (FoSTeS); f) non-homologous end joining (NHEJ); g) non-allelic homologous recombination (NAHR); h) micro-homology-mediated replication-dependent recombination (MMRDR); i) micro-homology-mediated break-induced repair (MMBIR); and j) losses or gains of chromosomes of ploidy, as reviewed in detail in 1 (See also Table S1). Exogenous factors such as tobacco and alcohol usage, and UV exposure may also be involved in postzygotic somatic mutational events37. We have divided these into four categories but recognize that the spectrum of variation is continuous, from a single nucleotide change to a diploid genome.