Bioinformatics Study Of SNP-based Detection Of Meiotic Recombination-Mediated Mutation And Selection

Meiotic recombination(recombination for short)is a tightly regulated cellular process that occurs programmatically during meiosis in eukaryotic cells.The process involves a series of molecular events such as chromosome breaks,physical contact between homologous chromosomes,and the exchange of genetic information.The formation of crossover between homologous chromosomes during recombination is necessary for proper chromosome segregation,and the production of aneuploidy is closely associated with recombination abnormalities.Meiotic recombination not only plays an important role in gametogenesis by assisting chromosome segregation,but is also an important source of genetic variation.Recombination is capable of both inducing mutations and promoting gene conversion between homologous chromosomes.In addition,recombination promotes the efficiency of natural selection by disrupting genetic linkage and optimizing gene combinations.Although the role of recombination in genome evolution has been studied for many years,some factors such as the resolution of recombination map and the exact molecular mechanism of recombination have a great impact on the understanding of "recombination-mediated genome evolution".In this paper,we investigated the role of recombination on the evolution of the human genome based on high resolution recombination map and SNP data of 1000 Genomes Project from two aspects: How does recombination shape SNP-related genomic features? Whether recombination drives genome evolution through a neighbor-dependent mutational bias?The main contents and results of this study are as follows:1.Based on the SNP data of 1000 Genomes Project(vcf files),by using tools such as VCFtools,Snp Eff,and SNPsift in combination with programming calculations,we investigated the mutational bias,the composition of the alleles at SNP loci,allele frequency in the population,and their relationships with recombination rates.It was found that:(1)T/A rare alleles were enriched in regions of high recombination rate,which was related to the C/G>T/A mutational bias caused by recombination;(2)The higher frequency of C/G alleles in the population compared to A/T alleles may be related to GC-biased gene conversion that occurs in the heteroduplex region formed during recombination,which facilitates the spread of the C/G alleles in the population.2.Recombination-associated selection was tested by analyzing the ratio between nonsynonymous substitution rate and synonymous substitution rate,nucleotide diversity,Tajima’s D,and heterozygosity at SNP loci.We found that:(1)the coding region is subject to stronger negative selection and has fewer rare alleles than the non-coding region;Recombination enhances negative selection in the coding region;(2)However,at the genome-wide level,genetic variants in regions with low recombination rates are subject to stronger negative selection than high recombination regions;(3)Gene set enrichment analysis showed that the genes strongly negatively selected under the influence of high recombination rates are involved in cell cycle,RNA processing and oocyte meiosis.3.Based on mutual information and conditional mutual information,we developed a method to quantitatively analyze the dependence of mutation on immediate adjacent bases(immediate neighbors).It was found that in the regions of high recombination rates,the immediate neighbor-dependent mutational bias was strengthened.We also provided a complete landscape of the dependence of recombination-related mutations on the immediate neighbors.To conclude,based on the recombination map with the highest resolution available,we revealed some recombination-associated evolutionary patterns and selection at genome-wide level.Our results provided supporting evidence for the recombination-mediated GC-biased gene conversion and suggested the presence of C/G>T/A mutational bias during recombination.