Bagshaw Andrew T M, Pitt Joel P W, Gemmell Neil J
School of Biological Sciences, University of Canterbury, New Zealand.
BMC Genomics. 2006 Jul 18;7:179. doi: 10.1186/1471-2164-7-179.
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. 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.
We 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.
Our 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.
减数分裂重组事件已被发现集中在1 - 2.5千碱基区域，但这些重组热点并不共享共有序列，且它们为何出现在特定位点尚未完全明确。先前的一些证据表明，多嘌呤/多嘧啶（poly-pu/py）序列（PPTs），一类具有独特生化特性的序列，可能参与重组，但此前尚未有关于PPTs与减数分裂重组热点普遍关联的报道。
我们使用计算方法详细研究了PPTs与热点之间的关系。我们展示了PPT频率与酿酒酵母基因组中减数分裂重组起始损伤（双链断裂）热点以及实验上特征明确的人类减数分裂重组热点之间的统计关联。支持富含poly-pu/py的序列在热点重组中可能发挥作用，我们还发现先前显示与人类热点活性变化相关的所有三个单核苷酸多态性都发生在14 bp或更长的序列背景中，这些序列85%或更多为poly-pu/py且至少70%为G/C。这些多态性都靠近热点中点。将实验特征明确的人类热点序列与先前显示不包含热点的黑猩猩基因组直系同源区域进行比较，我们发现，在所有五个可以利用公开可用序列数据对热点中心区域进行比较的案例中，在人类热点中点附近，14 bp或更长的序列存在差异，这些序列由超过80%的poly-pu/py和至少50%的G/C组成。
我们的结果，连同先前关于富含poly-pu/py的序列独特生化特性和重组刺激潜力的证据，表明这类序列在减数分裂重组热点中可能的功能参与值得进一步的实验探索。
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