During inter-locus gene conversion (GC), a nonreciprocal transfer of sequence information between a pair of nonallelic homologous DNA sequences takes place. One of the interacting sequences, the donor, remains unchanged, but the other sequence, the acceptor, gains a stretch of DNA copied from the donor. In addition to homogenizing the sequences of duplicons over time (evolution in consort; Ohta, PNAS 88:6716-6720, 1991), inter-locus GC is also responsible for spreading polymorphisms among gene copies. This process generates intra-species diversity and increases inter-species divergence. It also may lead to the inactivation of the acceptor locus when a pseudogene acts as a donor.
Similar to the non-uniform rate of crossovers across the genome, there is a large variation in GC activity among different duplicated regions, reflecting the regional potential to generate double-stranded breaks (DSB) triggering recombination. The study by Chuzhanova et al. in this issue (Hum Mutat 30:1189-1198, 2009) represents the first systematic analysis of DNA tracts involved in previously reported GC events. Their results support the hypothesis that it is not the DNA sequence motif per se that induces DSB, but its potential to form non-B DNA conformations (e.g., direct repeats promoting "slipped structures" or inverted repeats promoting hairpin/cruciform structures). Evidence that palindrome sequences forming hairpins are associated with DBS during GC was first published over 20 years ago (Krawinkel et al., NAR 14:3871-3882, 1986). New knowledge about the initiation of DBS and GC events is crucial to understanding the dynamics of duplicated genomic regions, hotspots for intra-and inter-species evolution, and human genetic disease.