Mitochondrial DNA (mtDNA) sequences from 686 wild and domestic pig specimens place the origin of wild boar in island Southeast Asia (ISEA), where they dispersed across Eurasia. Previous morphological and genetic evidence suggested pig domestication took place in a limited number of locations (principally the Near East and Far East). In contrast, new genetic data reveal multiple centers of domestication across Eurasia and that European, rather than Near Eastern, wild boar are the principal source of modern European domestic pigs.

Background The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model given its similarity in size, anatomy, physiology, metabolism, pathology, and pharmacology to humans. The draft reference genome (Sscrofa10.2) of a purebred Duroc female pig established using older clone-based sequencing methods was incomplete, and unresolved redundancies, short-range order and orientation errors, and associated misassembled genes limited its utility. Results We present 2 annotated highly contiguous chromosome-level genome assemblies created with more recent long-read technologies and a whole-genome shotgun strategy, 1 for the same Duroc female (Sscrofa11.1) and 1 for an outbred, composite-breed male (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than Sscrofa10.2. Conclusions These highly contiguous assemblies plus annotation of a further 11 short-read assemblies provide an unprecedented view of the genetic make-up of this important agricultural and biomedical model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference genome for genomic research in pigs.

38The domestic pig (Sus scrofa) is important both as a food source and as a biomedical model with high 39 anatomical and immunological similarity to humans. The draft reference genome (Sscrofa10.2) of a 40 purebred Duroc female pig established using older clone-based sequencing methods was incomplete 41 and unresolved redundancies, short range order and orientation errors and associated misassembled 42 genes limited its utility. We present two annotated highly contiguous chromosome-level genome 43 assemblies created with more recent long read technologies and a whole genome shotgun strategy, 44 one for the same Duroc female (Sscrofa11.1) and one for an outbred, composite breed male 45 (USMARCv1.0). Both assemblies are of substantially higher (>90-fold) continuity and accuracy than 46 Sscrofa10.2. These highly contiguous assemblies plus annotation of a further 11 short read assemblies 47 provide an unprecedented view of the genetic make-up of this important agricultural and biomedical 48 model species. We propose that the improved Duroc assembly (Sscrofa11.1) become the reference 49 genome for genomic research in pigs. 50 51 Keywords 52Pig genomes, reference assembly, pig, genome annotation 53 54 to the discovery of molecular genetic variants and the development of single nucleotide 59 polymorphism (SNP) chips [1] and enabled efforts to dissect the genetic control of complex traits, 60including responses to infectious diseases [2]. 61 62 Genome sequences are not only an essential resource for enabling research but also for applications 63 in the life sciences. Genomic selection, in which associations between thousands of SNPs and trait 64 variation as established in a phenotyped training population are used to choose amongst selection 65 candidates for which there are SNP data but no phenotypes, has delivered genomics-enabled genetic 66 improvement in farmed animals [3] and plants. From its initial successful application in dairy cattle 67 breeding, genomic selection is now being used in many sectors within animal and plant breeding, 68 including by leading pig breeding companies [4, 5]. 69 70The domestic pig (Sus scrofa) has importance not only as a source of animal protein but also as a 71 biomedical model. The choice of the optimal animal model species for pharmacological or toxicology 72 studies can be informed by knowledge of the genome and gene content of the candidate species 73 including pigs [6]. A high quality, richly annotated genome sequence is also essential when using gene 74 editing technologies to engineer improved animal models for research or as sources of cells and tissue 75 for xenotransplantation and potentially for improved productivity [7, 8]. 76 77The highly continuous pig genome sequences reported here are built upon a quarter of a century of 78 effort by the global pig genetics and genomics research community including the development of 79 recombination and radiation hybrid maps [9, 10], cytogenetic and Bacterial Artificial Chromosome 80 (BAC) physical maps [11, 12] and a draft referenc...

A F2 population derived from a cross between European Large White and Chinese Meishan pigs was established in order to study the genetic basis of breed differences for growth and fat traits. Chromosome 4 was chosen for initial study as previous work had revealed quantitative trait loci (QTLs) on this chromosome affected growth and fat traits in a Wild Boar x Large White cross. Individuals in the F2 population were typed for nine markers spanning a region of approximately 124 CM. We found evidence for QTLs affecting growth between weaning and the end of test (additive effect: 43.4 g/day) and fat depth measured in the mid-back position (additive effect: 1.82 mm). There was no evidence of interactions between the QTLs and sex, grandparents or F1 sires, suggesting that the detected QTLs were fixed for alternative alleles in the Meishan and Large White breeds. Comparison of locations suggests that these QTLs could be the same as those found in the Wild Boar x Large White cross.

The domestic pig (Sus scrofa) is both an economically important livestock species and a model for biomedical research. Two highly contiguous pig reference genomes have recently been released. To support functional annotation of the pig genomes and comparative analysis with large human transcriptomic data sets, we aimed to create a pig gene expression atlas. To achieve this objective, we extended a previous approach developed for the chicken. We downloaded RNAseq data sets from public repositories, down-sampled to a common depth, and quantified expression against a reference transcriptome using the mRNA quantitation tool, Kallisto. We then used the network analysis tool Graphia to identify clusters of transcripts that were coexpressed across the merged data set. Consistent with the principle of guilt-by-association, we identified coexpression clusters that were highly tissue or cell-type restricted and contained transcription factors that have previously been implicated in lineage determination. Other clusters were enriched for transcripts associated with biological processes, such as the cell cycle and oxidative phosphorylation. The same approach was used to identify coexpression clusters within RNAseq data from multiple individual liver and brain samples, highlighting cell type, process, and region-specific gene expression. Evidence of conserved expression can add confidence to assignment of orthology between pig and human genes. Many transcripts currently identified as novel genes with ENSSSCG or LOC IDs were found to be coexpressed with annotated neighbouring transcripts in the same orientation, indicating they may be products of the same transcriptional unit. The metaanalytic approach to utilising public RNAseq data is extendable to include new data sets and new species and provides a framework to support the Functional Annotation of Animals Genomes (FAANG) initiative.

Female reproductive performance traits in pigs have low heritabilities thus limiting improvement through traditional selective breeding programmes. However, there is substantial genetic variation found between pig breeds with the Chinese Meishan being one of the most prolific pig breeds known. In this study, three cohorts of Large White × Meishan F2 cross-bred pigs were analysed to identify quantitative trait loci (QTL) with effects on reproductive traits, including ovulation rate, teat number, litter size, total born alive and prenatal survival. A total of 307 individuals were genotyped for 174 genetic markers across the genome. The genome-wide analysis of the trait-recorded F2 gilts in their first parity/litter revealed one QTL for teat number significant at the genome level and a total of 12 QTL, which are significant at the chromosome-wide level, for: litter size (three QTL), total born alive (two QTL), ovulation rate (four QTL), prenatal survival (one QTL) and teat number (two QTL). Further support for eight of these QTL is provided by results from other studies. Four of these 12 QTL were mapped for the first time in this study: on SSC15 for ovulation rate and on SSC18 for teat number, ovulation rate and litter size.

Balancing selection provides a plausible explanation for the maintenance of deleterious alleles at moderate frequency in livestock, including lethal recessives exhibiting heterozygous advantage in carriers. In the current study, a leg weakness syndrome causing mortality of piglets in a commercial line showed monogenic recessive inheritance, and a region on chromosome 15 associated with the syndrome was identified by homozygosity mapping. Whole genome resequencing of cases and controls identified a mutation causing a premature stop codon within exon 3 of the porcine Myostatin (MSTN) gene, similar to those causing a double-muscling phenotype observed in several mammalian species. The MSTN mutation was in Hardy-Weinberg equilibrium in the population at birth, but significantly distorted amongst animals still in the herd at 110 kg, due to an absence of homozygous mutant genotypes. In heterozygous form, the MSTN mutation was associated with a major increase in muscle depth and decrease in fat depth, suggesting that the deleterious allele was maintained at moderate frequency due to heterozygous advantage (allele frequency, q = 0.22). Knockout of the porcine MSTN by gene editing has previously been linked to problems of low piglet survival and lameness. This MSTN mutation is an example of putative balancing selection in livestock, providing a plausible explanation for the lack of disrupting MSTN mutations in pigs despite many generations of selection for lean growth.

Lawsonia intracellularis is an obligate intracellular bacterial pathogen that causes proliferative enteropathy (PE) in pigs. L. intracellularis infection causes extensive intestinal crypt cell proliferation and inhibits secretory and absorptive cell differentiation. However, the affected host upstream cellular pathways leading to PE are still unknown. β-catenin/Wnt signalling is essential in maintaining intestinal stem cell (ISC) proliferation and self-renewal capacity, while Notch signalling governs differentiation of secretory and absorptive lineage specification. Therefore, in this report we used immunofluorescence (IF) and quantitative reverse transcriptase PCR (RTqPCR) to examine β-catenin/Wnt and Notch-1 signalling levels in uninfected and L. intracellularis infected pig ileums at 3, 7, 14, 21 and 28 days post challenge (dpc). We found that while the significant increase in Ki67+ nuclei in crypts at the peak of L. intracellularis infection suggested enhanced cell proliferation, the expression of c-MYC and ASCL2, promoters of cell growth and ISC proliferation respectively, was down-regulated. Peak infection also coincided with enhanced cytosolic and membrane-associated β-catenin staining and induction of AXIN2 and SOX9 transcripts, both encoding negative regulators of β-catenin/Wnt signalling and suggesting a potential alteration to β-catenin/Wnt signalling levels, with differential regulation of the expression of its target genes. We found that induction of HES1 and OLFM4 and the down-regulation of ATOH1 transcript levels was consistent with the increased Notch-1 signalling in crypts at the peak of infection. Interestingly, the significant down-regulation of ATOH1 transcript levels coincided with the depletion of MUC2 expression at 14 dpc, consistent with the role of ATOH1 in promoting goblet cell maturation. The lack of significant change to LGR5 transcript levels at the peak of infection suggested that the crypt hyperplasia was not due to the expansion of ISC population. Overall, simultaneous induction of Notch-1 signalling and the attenuation of β-catenin/Wnt pathway appear to be associated with the inhibition of goblet cell maturation and enhanced crypt cell proliferation at the peak of L. intracellularis infection. Moreover, the apparent differential regulation of apoptosis between crypt and lumen cells together with the strong induction of Notch-1 signalling and the enhanced SOX9 expression along crypts 14 dpc suggest an expansion of actively dividing transit amplifying and/or absorptive progenitor cells and provide a potential basis for understanding the development and maintenance of PE.