Slipped strand mispairing

Slipped strand mispairing (SSM) is a mutation process which occurs during DNA replication. It involves denaturation and displacement of the DNA strands, resulting in mispairing of the complementary bases. Slipped strand mispairing is one explanation for the origin and evolution of repetitive DNA sequences. Slipped strand mispairing has also been shown to function as a phase variation mechanism in certain bacteria.

SSM events can result in either insertions or deletions. Insertions are thought to be self-accelerating: as repeats grow longer, the probability of subsequent mispairing events increases. Insertions can expand simple tandem repeats by one or more units. In long repeats, expansions may involve two or more units. For example, insertion of a single repeat unit in GAGAGA expands the sequence to GAGAGAGA, while insertion of two repeat units in [GA]₆ would produce [GA]₈. Genomic regions with a high proportion of repeated DNA sequences (tandem repeats, microsatellites) are prone to strand slippage during DNA replication.

The combination of SSM events with point mutation is thought to account for the evolution of more complex repeat units. Mutations followed by expansion would result in the formation of new types of adjacent short tandem repeat units. For example, a transversion could change the simple two- base repeat [GA]₁₀ to [GA]₄GATA[GA]₂. This could then be expanded to[GA]₄[GATA]₃[GA]₂ by two subsequent SSM events. Simple repetitive DNA sequences containing a variety of adjacent short tandem repeats are commonly observed in non-protein coding regions of eukaryotic genomes.

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