Sequence heterology and gene conversion at his-3 of Neurospora crassa

Although sequence heterology clearly reduces crossing over in yeast, conflicting studies suggest that mismatches may increase or decrease gene conversion. To investigate this issue in an additional species, we measured the effect of local sequence heterology on conversion in his-3 of Neurospora crassa. Mismatches close to the cog recombination initiator or within his-3 reduce conversion to 70% and 30% of the homologous level, respectively, while heterologous insertions between his-3 and cog increase conversion by 20%. We suggest that, in both Neurospora and yeast, mismatches reduce the efficiency of the establishment and resolution stages of recombination, but substantial heterology may increase the progress of already established events by preventing repair synthesis from switching between templates. These data provide additional support that recombination at his-3 (and perhaps at yeast hotspots) proceeds by a synthesis-dependent strand-annealing mechanism, during which synthesis can switch templates, with the process being more tolerant of sequence mismatch in Neurospora.