Whole-genome Resequencing Provides Insight Into Itsartificial Selection Footprint

Animal domestication is a specific process by which captive animals adapt to human and the environment they provides. During domestication, a similar suite of traits tends to develop in diverse species, including modifications in behavior and other characteristics, such as reduced fear and increased stress tolerance were central in early domestication, and then increased production performance and reproductive capacity were the most important traits selected by human beings. A large number of livestock worldwide have undergone intensive natural and artificial selection in various environments and produced high levels of phenotypic diversity, constituting a valuable resource for investigating how selection affects the genome. With over 730 breeds or lines, domestic pig (Sus scrofa) is widely distributed over the world, providing plenty of meat production for human beings and can be used as model animal for medical research. Due to the economical and biomedical importance of domestic pigs, exploration of "domestication genes" is beneficial for agricultural development and medical research. For rapid and efficient accumulation of muscle and improvement of desirable pork qualities such as juiciness, flavor, tenderness, pink-hued and heavily marbled, a typical traditional European breed, Berkshire pig has undergone intensive artificial selection since the early 18th century in England. In this study, we performed genomic resequencing in three female Berkshire pigs, explored the genetic relationships among Berkshire and other pigs, and identified genetic components under selection that are likely the consequence of domestication of Berkshire pig. The results are as followings:1. A total of 36.65 Gb of paired-end DNA sequence were generated from Sequencing of three female Berkshire pigs, of which 36.29 Gb (99.02%) high quality paired-end reads were mapped to the pig reference genome assembly (Sus scrofa 10.2). Consequently, for each individual,78.75% of reads mapped to 79.39% of the reference genome assembly, with an average depth of 3.64-fold.2. In total,18.68 million (M) SNPs were identified in 41 individuals and divided into three groups:with 5.25 M from the 23 domestic pigs,5.47 M from the 13 wild boars, and 15.73 M from the four wild genus Sus and an African warthog. Only a small portion of (2.48 M of 18.68 M, or 13.28%) SNPs was shared among the three groups. Specifically, 3.65 M SNPs were identified from three Berkshire pigs, of which 21,905 coding SNPs leading to 7,773 nonsynonymous nucleotide substitutions (7,713 missense,44 stop gain and 16 stop loss) were detected in 3,978 genes.3. We also identified 2.93 M small insertion or deletion polymorphisms (InDels) ranging from 1～30 bp in length. Only 2,991 (0.10%) InDels were located in coding sequences, of which 29.35% were multiples of 3 bp. These InDels affected genes enriched mainly in terms related to basic cellular functions, such as the ’binding of adenyl nucleotide, purine nucleoside, ATP, cation, ion, metal ion, and nucleoside’ and ’protein kinase activity’.4. To explore relatedness of 41 individulas, we conducted principle component analysis (PCA) using genomic SNPs. The first eigenvector geographically distinguishes 23 individuals in Europe from 17 individuals in Asian and a warthog in Africa, while the second eigenvector captures the biological differentiation between pigs (including domestic and wild boar) and other outgroup. Admixture analysis revealed that Berkshire pig exhibited a stronger signal of introgression from Chinese domestic pig than other European domestic pigs, with excess of ABBA sites (0<D<1).5. The lower levels of linkage disequilibrium (LD) was observed in Berkshire pigs compared with the wild boars, reflecting a relatively lower genomic diversity in Berkshire pig. Meanwhile, a total of 11.95 Mb genomic regions (4.75% of the genome, containing 482 genes) were identified with strong selective sweep signals in Berkshire pigs, which also exhibited significant differences (P<10-16, Mann-Whitney U test) in log2(θπratio)and FST values when compared to genomic background. Totally,482 genes embedded in selected regions were predominantly related to immune (such as ’defense response to virus (4 genes, P=0.001)’ and ’Immunoglobulin’(11 genes, P=0.001), growth(such as ’regulation of growth (11 genes, P=0.003)’), reproduction (such as ’oocyte meiosis (6 genes, P=0.004)’).6. In addition, eight genes exhibiting strong selective sweep signals are significantly over-represented in human height-associated’OMIM-disease term:Many sequence variants affecting diversity of adult human height’(P=0.002), including ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type Ⅰ motifs-like 3), GPR126 (G-protein coupled receptor 126), PRKG2 (cGMP-dependent type Ⅱ protein kinase), IGF1 (Insulin-like growth factor 1), et al.This study presented the genetic relationships between the Berkshire and other pigs, and uncovered genetic footprints of domestication that provide an important resource for further improvements of this important livestock species. The work performed here will serve as typical demonstration for future deciphering the genomic differences shaped by the artificial selections.