ABO 遺伝子型はブタの GalNAc レベルを調節することで腸内細菌叢を変化させる

2-fold higher in domestic pigs than in human populations, as previously reported111,112,113. Nucleotide diversities between Chinese founder breeds and between European founder breeds were ~3.6x10−3 and ~2.5x10−3, respectively, i.e. 1.44-fold and 1.25-fold higher than the respective within-breed π-values. These π-values are of the same order of magnitude as the sequence divergence between Homo sapiens and Neanderthals/Denosivans (~3x10−3, ref. 15). By comparison, π-values between Africans, Asians and Europeans are typically ≤ ~1x10−3 (ref. 109). The nucleotide diversity between Chinese and European breeds averaged ~4.3x10−3. This π-value is similar to the divergence between M. domesticus and M. castaneus114, and close to halve the ~1% difference between chimpanzee and human16. Note that Chinese and European pig breeds are derived from Chinese and European wild boars, respectively, which are thought to have diverged ~1 million years ago27, while M. domesticus and M. castaneus are thought to have diverged ≤ 500,000 years ago114. (d) Autosome-specific estimates of the genomic contributions of the eight founder breeds in the F6 and F7 generation. We used a linear model incorporating all variants to estimate the average contribution of the eight founder breeds in the F6 and F7 generation at genome and chromosome level56. At genome-wide level, the proportion of the eight founder breed genomes ranged from 11.2% (respectively 11.5%) to 14.1% (14.7%) in the F6 (F7) generations. At chromosome-specific level, the proportion of the eight founder breeds ranged from 6.7% (respectively 4.9%) to 20.7% (22.1%) in the F6 (F7) generations. The genomic contribution of the eight founder breeds in the F6 and F7 generation is remarkably uniform and close to expectations (i.e. 12.5%) both at genome-wide and chromosome-wide level, suggesting comparable levels of genetic diversity across the entire genome. This does not preclude that more granular examination may reveal local departures from expectations, or under-representation of incompatible allelic combinations at non-syntenic loci. (e-f) Indicators of achievable mapping resolution in the F6 generation: (e) Frequency distribution (density) of the number of variants in high LD (r2 ≥ 0.9) with an “index” variant (was computed separately for all variants considered sequentially as the “index”), corresponding to the expected size of “credible sets” in GWAS115. The red vertical line corresponds to the genome-wide median. The green vertical line corresponds to the mapping resolution achieved in this study for the ABO locus (see hereafter). (f) Frequency distribution (density) of the maximum distance between an index variant and a variant in high LD (r2 ≥ 0.9) with it, defining the spread of credible sets. Red and green vertical lines are as in (D)./p>95% of day 120 and 240 faeces and caecum content samples of both F6 and F7 generations, hence defined as core bacterial taxa. (b) The compositions of the porcine and human intestinal microbiota are closer to each other than either is to that of the mouse. Boxplots are as is Fig. 1c. The number of samples available for analysis were 1281 pigs, 106 humans and 6 mice. (c) Abundances (F6-F7 averages when available) of the 43 families represented in Fig. 1b in the seven sample types relative to the sample type in which they are the most abundant (red – blue scale). The families are ordered according to the sample type in which they are the most abundant. The colour-code for phyla is as in Fig. 1b. Columns are added for comparison with mouse and human. Mouse data are from Fig. 1 in Suzuki & Nachman116, and human data from Fig. 6 in Vuik et al117. P_I: proximal ileum, D_IL: distal ileum, C: caecum, CO: colon, RE: rectum, F: faeces. The families differing the most with regards to location-specific distribution between species include Helicobacteriaceae, Veillonellaceae, Lactobacillaceae and Streptocaccaceae./p> 10 MYA. It will be interesting to study larger numbers of warthog to see whether the same 2.3 kb deletion exists in this and other related species as well. (b) Alignment of ~900 base pairs of the O alleles of domestic pigs (Bamaxian), European and Asian wild boars, and Sus cebufrons demonstrating that these are identical-by-descent. The SINE element that is presumed to have mediated the recombinational event that caused to 2.3 kb deletion is highlighted in red. Context: To further support their identity-by-descent we aligned ~900 base pairs (centred on the position of the 2.3 kb deletion) of the O alleles of domestic pig, European and Asian wild boars and Sus cebifrons. The sequences were nearly identical further supporting our hypothesis. It is noteworthy that the old age of the “O” allele must have contributed to the remarkable mapping resolution (≤3 kb) that was achieved in this study. In total, 42 variants were in near perfect LD (r2 ≥ 0.9) with the 2.3 kb deletion in the F0 generation, spanning 2,298 bp (1,522 on the proximal side, and 762 on the distal side of the 2.3 kb deletion). This 2.3 kb span is lower than genome-wide expectations (17th percentile), presumably due to the numerous cross-overs that have accrued since the birth of the 2.3 kb deletion that occurred in the distant past. Yet the number of informative variants within this small segment is higher than genome-wide average of (57% percentile) also probably due at least in part to the accumulation of numerous mutations since the remote time of coalescence of the A and O alleles (see Fig. 1d in main text). (c) QQ plots for the effect of AO genotype on 150 phenotypes pertaining to meat quality, growth, carcass composition, hematology, health, and other phenotypes in the F6 and F7 generation. P-values were obtained using a mixed model followed by meta-analysis (weighted Z score) across the F6 and F7 generations as described in Methods. log-transformed p-values used for the QQ plot are nominal and two-sided. Context: Our findings in suidae are reminiscent of the trans-species polymorphism of the ABO gene in primates attributed to balancing selection26. The phenotype driving balancing selection remain largely unknown yet a tug of war with pathogens is usually invoked: synthesized glycans may affect pathogen adhesion, toxin binding or act as soluble decoys, while naturally occurring antibodies may be protective20,44. In humans, the O allele may protect against malaria118, E. Coli and Salmonella enteric infection119, SARS-CoV-142, SARS-CoV-243 and schistosomiasis120,121,122, while being a possible risk factor for cholera123, H. pylori124 and norovirus infection125. Whatever the underlying selective force, it appears to have operated independently in at least two mammalian branches (primates and suidae), over exceedingly long periods of time, and over broad geographic ranges, hence pointing towards its pervasive nature. To gain insights in what selective forces might underpin the observed balanced polymorphism, we tested the effect of porcine AO genotype on >150 traits measured in the F6 and F7 generations pertaining to carcass composition, growth, meat quality, hematological parameters, disease resistance and behaviour. No significant effects were observed when accounting for multiple testing, including those pertaining to immunity and disease resistance. (d) Expression profile of the AO gene in a panel of adult and embryonic porcine tissues (own RNA-Seq data)./p>