High negative interference (HNI), in contrast to positive interference, refers to the association of recombination events ordinarily measured over short genomic distances, usually within a gene. Over such short distances there is a positive correlation (negative interference) of recombinational events. As studied in bacteriophage T4 this correlation is greater the shorter the interval between the sites used for detection. HNI is due to multiple exchanges within a short region of the genome during an individual mating event. What is counted as a “single exchange” in a genetic cross involving only distant markers may in reality be a complex event that is distributed over a finite region of the genome. Switching between template DNA strands during DNA synthesis (see Figure, SDSA pathway), referred to as copy-choice recombination, was proposed to explain the positive correlation of recombination events within the gene. HNI appears to require fairly precise base complementarity in the regions of the parental genomes where the associated recombination events occur.
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