Abstract
BackgroundMeiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Some previous evidence suggests that poly-purine/poly-pyrimidine (poly-pu/py) tracts (PPTs), a class of sequence with distinctive biochemical properties, could be involved in recombination, but no general association of PPTs with meiotic recombination hot spots has previously been reported.ResultsWe used computational methods to investigate in detail the relationship between PPTs and hot spots. We show statistical associations of PPT frequency with hot spots of meiotic recombination initiating lesions, double-strand breaks, in the genome of the yeast S. cerevisiae and with experimentally well characterized human meiotic recombination hot spots. Supporting a possible role of poly-pu/py-rich sequences in hot spot recombination, we also found that all three single nucleotide polymorphisms previously shown to be associated with human hot spot activity changes occur within sequence contexts of 14 bp or longer that are 85% or more poly-pu/py and at least 70% G/C. These polymorphisms are all close to the hot spot mid points. Comparing the sequences of experimentally characterized human hot spots with the orthologous regions of the chimpanzee genome previously shown not to contain hot spots, we found that in all five cases in which comparisons for the hot spot central regions are possible with publicly available sequence data, there are differences near the human hot spot mid points within sequences 14 bp or longer consisting of more than 80% poly-pu/py and at least 50% G/C.ConclusionOur results, along with previous evidence for the unique biochemical properties and recombination-stimulating potential of poly-pu/py-rich sequences, suggest that the possible functional involvement of this type of sequence in meiotic recombination hot spots deserves further experimental exploration.
Highlights
Meiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood
We found that the three single nucleotide changes shown to be associated with human hot spot recombination rates all occur in high GC-content poly-pu/py-rich sequences of at least 14 bp, and that sequence differences between humans and chimpanzees in regions where there is a hot spot in humans but none in chimpanzees occur in similar poly-pu/py-rich sequence contexts
This study identified 303 hot and 49 cold open reading frames (ORFs), and, combining adjacent ones, defined 177 hot spots, which encompassed all previously known hot spots in the species, and 40 cold spots
Summary
Meiotic recombination events have been found to concentrate in 1–2.5 kilo base regions, but these recombination hot spots do not share a consensus sequence and why they occur at specific sites is not fully understood. Crossovers between chromosomes occur during meiotic cell division resulting in heritable genetic recombination These crossovers have a complex, non-random distribution, and in the last decade recombination hot spots 1– 2.5 kilo bases (kb) wide have been experimentally well (page number not for citation purposes). Hot spots do not share a consensus sequence, and the mechanisms responsible for regulating their distribution and activity levels are not well understood, but several molecular features of hot spot recombination have been described (reviewed in [6]) These include a locally open chromatin structure, presumably allowing access to recombination machinery [7,8], and a requirement for a chromosomal double-strand break (DSB) to initiate recombination [9,10]. This suggests that epigenetic, or distal sequence, factors may have a greater influence than local sequences on hot spot regulation, and consistent with this idea are recent studies showing that the locations of hot spots in humans and chimpanzees do not correspond despite more than 98% sequence similarity between the two species [14,15]
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