The composition of the intestinal microbiome varies considerably between individuals and is correlated with health 1 . Understanding the extent to which, and how, host genetics contributes to this variation is essential yet has proved to be difficult, as few associations have been replicated, particularly in humans 2 . Here we study the effect of host genotype on the composition of the intestinal microbiota in a large mosaic pig population. We show that, under conditions of exacerbated genetic diversity and environmental uniformity, microbiota composition and the abundance of specific taxa are heritable. We map a quantitative trait locus affecting the abundance of Erysipelotrichaceae species and show that it is caused by a 2.3 kb deletion in the gene encoding N -acetyl-galactosaminyl-transferase that underpins the ABO blood group in humans. We show that this deletion is a ≥3.5-million-year-old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N -acetyl-galactosamine in the gut, and thereby reduces the abundance of Erysipelotrichaceae that can import and catabolize N -acetyl-galactosamine. Our results provide very strong evidence for an effect of the host genotype on the abundance of specific bacteria in the intestine combined with insights into the molecular mechanisms that underpin this association. Our data pave the way towards identifying the same effect in rural human populations.

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Background Short tandem repeats (STRs) are genetic markers with a greater mutation rate than single nucleotide polymorphisms (SNPs) and are widely used in genetic studies and forensics. However, most studies in pigs have focused only on SNPs or on a limited number of STRs. Results This study screened 394 deep-sequenced genomes from 22 domesticated pig breeds/populations worldwide, wild boars from both Europe and Asia, and numerous outgroup Suidaes, and identified a set of 878,967 polymorphic STRs (pSTRs), which represents the largest repository of pSTRs in pigs to date. We found multiple lines of evidence that pSTRs in coding regions were affected by purifying selection. The enrichment of trinucleotide pSTRs in coding sequences (CDS), 5′UTR and H3K4me3 regions suggests that trinucleotide STRs serve as important components in the exons and promoters of the corresponding genes. We demonstrated that, compared to SNPs, pSTRs provide comparable or even greater accuracy in determining the breed identity of individuals. We identified pSTRs that showed significant population differentiation between domestic pigs and wild boars in Asia and Europe. We also observed that some pSTRs were significantly associated with environmental variables, such as average annual temperature or altitude of the originating sites of Chinese indigenous breeds, among which we identified loss-of-function and/or expanded STRs overlapping with genes such as AHR, LAS1L and PDK1. Finally, our results revealed that several pSTRs show stronger signals in domestic pig—wild boar differentiation or association with the analysed environmental variables than the flanking SNPs within a 100-kb window. Conclusions This study provides a genome-wide high-density map of pSTRs in diverse pig populations based on genome sequencing data, enabling a more comprehensive characterization of their roles in evolutionary and environmental adaptation.

Background Meat production from the commercial crossbred Duroc × (Landrace × Yorkshire) (DLY) pig is predominant in the pork industry, but its meat quality is often impaired by low ultimate pH (pHu). Muscle glycogen level at slaughter is closely associated with pHu and meat technological quality, but its genetic basis remains elusive. The aim of this study was to identify genes and/or causative mutations associated with muscle glycogen level and other meat quality traits by performing a genome-wide association study (GWAS) and additional analyses in a population of 610 DLY pigs. Results Our initial GWAS identified a genome-wide significant ( P = 2.54e−11) quantitative trait locus (QTL) on SSC15 (SSC for Sus scrofa chromosome) for the level of residual glycogen and glucose (RG) in the longissimus muscle at 45 min post-mortem. Then, we demonstrated that a low-frequency (minor allele frequency = 0.014) R200Q missense mutation in the PRKAG3 ( RN ) gene caused this major QTL effect on RG. Moreover, we showed that the 200Q ( RN – ) allele was introgressed from the Hampshire breed into more than one of the parental breeds of the DLY pigs. After conditioning on R200Q, re-association analysis revealed three additional QTL for RG on SSC3 and 4, and on an unmapped scaffold (AEMK02000452.1). The SSC3 QTL was most likely caused by a splice mutation (g.8283C>A) in the PHKG1 gene that we had previously identified. Based on functional annotation, the genes TMCO1 on SSC4 and CKB on the scaffold represent promising candidate genes for the other two QTL. There were significant interaction effects of the GWAS tag SNPs at those two loci with PRKAG3 R200Q on RG. In addition, a number of common variants with potentially smaller effects on RG ( P < 10 −4 ) were uncovered by a second conditional GWAS after adjusting for the two causal SNPs, R200Q and g.8283C>A. Conclusions We found that the RN – allele segregates in the parental lines of our DLY population and strongly influences its meat quality. Our findings also indicate that the genetic basis of RG in DLY can be mainly attributed to two major genes ( PRKAG3 and PHKG1 ), along with many minor genes. Electronic supplementary material The online version of this article (10.1186/s12711-019-0488-0) contains supplementary material, which is available to authorized users.

Huanfa Gong and Weiwei Liu contributed equally to this study.

SummaryWe have generated a large heterogenous stock population by intercrossing eight divergent pig breeds for multiple generations. We have analyzed the composition of the intestinal microbiota at different ages and anatomical locations in > 1,000 6th- and 7th- generation animals. We show that, under conditions of exacerbated genetic yet controlled environmental variability, microbiota composition and abundance of specific taxa (including Christensenellaceae) are heritable in this monogastric omnivore. We fine-map a QTL with major effect on the abundance of Erysipelotrichaceae to chromosome 1q and show that it is caused by a common 2.3-Kb deletion inactivating the ABO acetyl-galactosaminyl-transferase gene. We show that this deletion is a trans-species polymorphism that is ≥3.5 million years old and under balancing selection. We demonstrate that it acts by decreasing the concentrations of N-acetyl-galactosamine in the cecum thereby reducing the abundance of Erysipelotrichaceae strains that have the capacity to import and catabolize N-acetyl-galactosamine.

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Background Short tandem repeats (STRs) were recently found to have significant impacts on gene expression and diseases in humans, but their roles on gene expression and complex traits in pigs remain unexplored. This study investigates the effects of STRs on gene expression in liver tissues based on the whole-genome sequences and RNA-Seq data of a discovery cohort of 260 F6 individuals and a validation population of 296 F7 individuals from a heterogeneous population generated from crosses among eight pig breeds. Results We identified 5203 and 5868 significantly expression STRs (eSTRs, FDR < 1%) in the F6 and F7 populations, respectively, most of which could be reciprocally validated (π1 = 0.92). The eSTRs explained 27.5% of the cis-heritability of gene expression traits on average. We further identified 235 and 298 fine-mapped STRs through the Bayesian fine-mapping approach in the F6 and F7 pigs, respectively, which were significantly enriched in intron, ATAC peak, compartment A and H3K4me3 regions. We identified 20 fine-mapped STRs located in 100 kb windows upstream and downstream of published complex trait-associated SNPs, which colocalized with epigenetic markers such as H3K27ac and ATAC peaks. These included eSTR of the CLPB, PGLS, PSMD6 and DHDH genes, which are linked with genome-wide association study (GWAS) SNPs for blood-related traits, leg conformation, growth-related traits, and meat quality traits, respectively. Conclusions This study provides insights into the effects of STRs on gene expression traits. The identified eSTRs are valuable resources for prioritizing causal STRs for complex traits in pigs.