Minimal repeat sequences are ubiquitous sites of unequal crossover and recombination across the human genome

Background We previously reported that a major portion of trinucleotide two-repeat units (TTUs) are sites of unequal crossover and consequent colonization, that are massively spread and shared across the genomes of human and several other primates. These sites underscore the preference of AT- over CG-rich sequences, as recombination sites. Methods Here we extended our study to dinucleotides of AT/TA and CG/GC. An algorithm was designed to extract genomic regions with a higher probability of recombination. To this end, the algorithm consisted of dinucleotide 3-repeat units (D3Us), a portion of which was hypothesized to be the basic overlapping units, resulting from unequal crossover between dinucleotide two-repeat units (D2Us). We mapped TATATA, ATATAT, CGCGCG, and GCGCGC across the human genome, and analyzed their colonization (distance between consecutive D3Us < 500 bp). We also studied several colonies of various sizes in up to 100 vertebrates, using the UCSC and ENSEMBL Genome Browsers. Results We found 3,989,861 AT/TA and 95,849 CG/GC D3Us across the human genome, the majority of which resided in over 480,000 colonies, ubiquitously spread along all chromosomes. The AT/TA colonies were significantly larger and more intricate than CG/GC colonies. These colonies were mainly specific to, or of their largest size in human. D2Us and D3Us were the primary sites of unequal crossover in these colonies, resulting in the emergence of primary recombinants (overlaps among AT/TA repeats), ranging from 5- to 15-bp, and a vast repertoire of secondary recombinants (recombination among pure and primary recombinants), and eventually, colonies of exceeding intricacy and significance, based on Poisson distribution. Conclusion We report ubiquitous and intricate colonies of exceeding significance, in which D2Us and D3Us were the primary sites of unequal crossover and recombination. Across vertebrates, these colonies reached their maximum size in human. It is plausible that minimal DNA repeat sequences, such as D2Us, D3Us, and TTUs, mark recombination a ubiquitous rule across the human genome. This phenomenon may transform our perception of recombination, its magnitude, and biological and evolutionary consequences.