Dependence Of Meiotic Recombination On DNA Sequence And Chromatin Structure

Meiotic recombination is a kind of recombination. It is the exchange of geneticinformation between homologous chromosomes, which occurs during the meiosis ofeukaryotic cells. Meiotic recombination does not occur evenly across the genome, butinstead occurs at relatively high frequencies in some genomic regions (hotspots) andrelatively low frequencies in others (coldspots). About80%of a eukaryotic genome appearsto be covered by nucleosomes. The pattern of nucleosome positioning and dynamics ofnucleosomes have a direct influence on the contact between protein and DNA, and thus thenucleosomes play an important role in DNA replication, transcription and recombination.Hence, recombination depends not only on DNA sequence features, but also on chromatinstructure. Identification and characterization of hotspots and coldspots are considerablysignificant as the information about hot/cold spots would shed light on the mechanism ofrecombination and genome evolution. Determination of high-resolution recombination ratesusing genetic experiments is time-consuming and expensive. Thus, it is necessary to developcomputational methods to predict recombination rates or recombination hotspots in thegenome. This thesis includes the following aspects：1. We analyzed the correlation between recombination and nucleosome occupancy, andmade a couple of predictions for recombination hotspots by IDQD approach based on thetetranucleotide frequencies and nucleosome occupancy. We found that genome-widerecombination rate shows an increasing tendency with the increasing of nucleosomeoccupancy in yeast (R=0.151, P<0.001), and correlations between recombination rate andnucleosome occupancy on coding sequences and intergenic sequences are also significant.That means recombination occurs more easily in the regions with high nucleosomeoccupancy. The prediction accuracy for hotspots based on DNA sequence alone is80%. Theprediction accuracy increased to81.6%when nucleosome occupancy is used as an additionalfeature. Our results indicate that chromatin structure, apart from DNA sequence, is anotherfactor which has significant effect on meiotic recombination in yeast. And these predictions indicate that kilo-base scale nucleosome occupancy has a significant effect on recombinationin yeast.2. We redefined the hot/cold spots sequences, and made a series of predictions forrecombination hotspots by IDQD approach and SVM approach based on dinucleotidepreference, GC content, Gibbs free energy, DNA structure parameters,4-mer frequenciesand nucleosome occupancy. Our results indicate that dependence of recombination onsequence features and chromatin structure is significant. Prediction for hotspots based on4-mer frequencies, Gibbs free energy and nucleosome occupancy is better than otherpredictions, and the prediction accuracy is76%. That means the predicton accuracy based onsequence features and chromatin structure is better than the prediction accuracy based oneither sequence features or chromatin structure. And IDQD approach is better than SVMapproach in these predictions for hotspots, as the sensitivity of SVM is very bad.