Crossover interference is the term used to refer to the non-random placement of crossoverswith respect to each other during meiosis. The term is attributed to Muller, who observed that one crossover "interferes with the coincident occurrence of another crossing over in the same pair of chromosomes, and I have accordingly termed this phenomenon ‘interference’." Meiotic crossovers appear to be regulated to ensure that COs on the same chromosome are distributed far apart. In the nematode wormCaenorhabditis elegans, meiotic double-strand breaks outnumber COs. Thus not all DSBs are repaired by a recombination process leading to COs. The RTEL-1 protein is required to prevent excess meiotic COs. In rtel-1 mutants meiotic CO recombination is significantly increased and crossover interference appears to be absent. RTEL1 likely acts by promoting synthesis-dependent strand annealing which results in non-crossover recombinants instead of COs. Normally, about half of all DSBs are converted into NCOs. RTEL-1 appears to enforce meiotic crossover interference by directing the repair of some DSBs towards NCOs rather than COs. In humans, recombination rate increases with maternal age. Furthermore, placement of female recombination events appears to become increasingly deregulated with maternal age, with a larger fraction of events occurring within closer proximity to each other than would be expected under simple models of crossover interference.
High negative interference
Bacteriophage T4
High negative interference, in contrast to positive interference, refers to the association of recombination events ordinarily measured over shortgenomic distances, usually within a gene. Over such short distances there is a positive correlation 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, 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.
HIV
Each human immunodeficiency virus particle contains two single-stranded positive senseRNA genomes. After infection of a host cell, a DNA copy of the genome is formed by reverse transcription of the RNA genomes. Reverse transcription is accompanied by template switching between the two RNA genome copies. From 5 to 14 recombination events per genome occur at each replication cycle. This recombination exhibits HNI. HNI is apparently caused by correlated template switches during minus-strand DNA synthesis. Template switching recombination appears to be necessary for maintaining genome integrity and as a repair mechanism for salvaging damaged genomes.
