On the molecular basis of high negative interference.

Two models designed to account for high negative interference phenomena have been examined. One proposal suggests that many recombination events are the result of insertion of a small single-stranded segment of DNA into a recipient molecule. An alternative explanation for the clustering of genetic exchanges is reduction to homozygosity of genetically heterozygous sites appearing within heteroduplex overlap regions. These proposals have been examined in phage lambda by analyzing the structure of unduplicated recombinants arising from three-factor crosses with tightly linked markers. Double recombinants are found to have received substantial contributions of DNA from both parents. In addition, their patterns of genetic heterozygosity are not readily reconcilable with a single-strand insertion hypothesis. Reconstruction experiments with artifically constructed heteroduplex heterozygotes support the reduction to homozygosity hypothesis and specify the strand polarity of the heterozygous overlap region.