Study On Molecular Genetic Mechanism Of Litter Size In Sheep

Litter size is an important trait in sheep breeding,which is a key index to improve productivity and benefit.Litter size is a compound quantitative trait controlled by micro-effect polygene;it is difficult for traditional breeding methods to achieve efficient directional breeding to improve the litter size.In this study,the whole genome-gene pathway-single gene research route was adopted.Based on the whole genome selection signal detection,candidate genes of the litter size were mined,in order to analyze the molecular mechanism of prolific trait of sheep.This study aimed to provide candidate genes or genetic markers for the efficient breeding of litter size,it is of great significance for the breeding of prolific sheep breed and the efficient development of mutton sheep industry.In this study,a total of 40 Hu sheep were selected from 400 Hu sheep ewes,and divided into two groups(single lamb and multiple lamb).The whole genome re-sequencing was performed,and candidate genes for the litter size were screened by the selection signal detection.Transcriptome sequencing and selection analysis were used to analyze the transcriptional level of BMP-BMPR-Smad signaling pathway gene and ZP3 gene in gonadal axis tissue of Hu sheep ewes and the selection signal among species and sheep populations.Based on the change of effective population size during Mongolian sheep migration and the estimation of FecB mutation age of BMPR1B gene,the selection effect of FecB mutation site was analyzed.The main results of this study are as follows:(1)47 candidate genes of the litter size including BMP2,BMP5,BMPR1B and ZP3 gene were screened through genome-wide selection signal detection;(2)BMP2,BMP5,BMP6,BMP7,BMPR1 A,BMPR1B,Smad1,Smad4 and Smad5 genes were under purifying selection among species,but positive selection among sheep populations;(3)the estimation of allele age indicated that the FecB mutation occurred at about 5000 years ago,and the effective population size of Mongolian sheep population had been reduced twice,which happened about 1.6 and 1.0 thousand years ago respectively.According to historical records,the temperature dropped sharply in these two periods.The results of Meta-analysis and regression analysis showed that the allele frequency of FecB mutation was significantly correlated with litter size and latitude(p<0.05).The FecB mutation site was under purifying selection among species,but positive selection among sheep populations;(4)a non-synonymous mutation site(rs401271989)was detected in ZP3 gene in this study,which was significantly correlated with the first parity litter size of Hu sheep(p<0.05).The main conclusions of this study are as follows:(1)the litter size of sheep is controlled by polygenes,47 candidate genes(including BMP2,BMP5,BMPR1B and ZP3 gene)for litter size were screened;(2)the FecB mutation of BMPR1B gene significantly affected the litter size of sheep,with each copy increasing by 0.4-0.5.This mutation occurred about 5000 years ago,and with the migration of Mongolian sheep from Mongolian Plateau to Yangtze River Basin,the relaxation of selection pressure drives FecB mutation to spread rapidly in the population,and its allele frequency was negatively correlated with latitude;(3)the non-synonymous mutation site(rs401271989)in ZP3 gene of Hu sheep is significantly related to the first parity litter size,which can to be used as a molecular marker for the litter size breeding.In conclusion,BMPR1B and ZP3 gene can be used as major gene or candidate gene for litter size in gene selection or molecular marker assisted selection,in order to improve the accuracy of prolific sheep breeding.