Identification Of Genes Related To Prolificacy In French Large White Pigs Using Whole-genome Resequencing Approache

European and Asian wild boars have been independently domesticated for nearly 10,000 years,resulting in a variety of pig breeds under different geographical and climatic conditions and human activities.China has the most aboundant pig genetic resources in the world,accounting for one third of global pig breeds.There have been several historical gene flows between Chinese and European domestic pigs and wild boars.The human-mediated introgression of Chinese pigs into Europe has made significant contribution to the formation of modern commercial pig breeds.French Large White(FLW)is known for its prolificacy,which is presumably attributable to the recent introgression of Chinese prolific Meishan pigs into this breed.To test this assumption,we herein explored high-depth re-sequencing data of 266 European and Asian pigs to uncover the intogression signals across the gonome of FLW and investigate the association of these signals with phenotypic traits in FLW pigs.First,we collected ear tissue samples of 36 prolific FLW pigs from two populations and harvested samples of 111 pigs from 13 Chinese indigenous breeds and 6 Chinese wild boars.These 153 individuals were resequenced at 25� depth.Then,we downloaded publicly available genome data of 113 European and Chinese domestic pigs and wild boars.The two data set were merged into a final 266-individual data set.A total of 19,375,740 SNPs were identified in the final data set using the GATK software.These SNPs were used for subsequent statistical analyses.We confirmed the significant genetic differentiation between Chinese and Western domestic pigs and the differentiation between East(Meishan,Erhualian and Jinhua pigs)and South(Luchuan,Bamaxiang and Wuzhishan pigs)Chinese domestic pigs using principal component analysis,neighbor-joining tree analysis,ADMIXTURE and TreeMix analysis.Then,through a genome-wide shared IBD haplotype analysis(rIBD),we detected the introgressed lineages in the genomes of French Large White pigs from East and South Chinese domestic pigs,respectively.According to the historical document and the hyplotypes length analysis,we found that South Chinese(SCN)pigs was introduced into FLW pigs earlier than East Chinese(ECN)pigs.We estimated that approximately 0.9% of ancestral lineage of FLW pigs were introduced from ECN pigs.The KATNAL1 gene is located in one of three regions that showed the most significant rIBD signal.This gene is functionally related to sperm formation and activity.Next,we confirmed that the KATNAL1 haplotype originated from ECN pigs was intregressed into FLW pigs and this haplotype has been strongly selected in FLW pigs.Further,we showed that the KATNAL1 haplotype from ECN pigs significantly increase litter size with an additive effect of 0.4 in sows,which has the great potential for further genetic improvement in pigs.We also used the above-mentioned methods to detect the introgression signals from SCN pigs into FLW pigs.Antiviral-associated NAA35-GOLM1 haplotypes on chromosome 10 and ATP-associated ATP5 H haplotypes on chromosome 16 have been introgressed from SCN pigs into FLW pigs,and afterwards,has also been strongly selected,likely contributing to the genetic improvement of disease resistance and energy balance in FLW pigs.Finally,we conducted an in-depth analysis for the previously reported AHR introgression region.We found that Chinese AHR haplotypes in Large White pigs(including FLW pigs)were distributed in ECN pigs at high frequencies.Through a series of analysis including allele frequency differences,gene flow(fD),haplotype network and nucleotide distance(Dxy),we unexpectely found that AHR haplotype from ECN pigs was an ancient haplotype.This haplotype was originated from another possibly extinct Sus species,and the introgressed region has been strongly selected in FLW pigs during recent years.We further confirmed that the ancient AHR haplotype was significantly associated with the litter size EBV in multiparity sows.Notably,the additive effect of this haplotype was 0.25,indicating that the haplotype could increase the yield of 0.25 piglets per sow per parity and had a high economical value for pig breeding.