Complex mutational events, including de novo inversion with deletion a
nd duplication of sequence, have been observed but are difficult to mo
del. We propose that nascent leading-strand misalignment upon the lagg
ing-strand template during DNA replication can result in the inversion
of sequence. The positioning of this misalignment and of the realignm
ent of the leading strand back onto the leading-strand template will d
etermine if the inversion is accompanied by deletion and duplication o
f sequence. We suggest that such strand misalignment-realignment event
s may occur at the replication fork during concurrent DNA replication.