Population history and genomic signatures for high-altitude adaptation in Tibetan pigs

Abstract

Background: The Tibetan pig is one of domestic animals indigenous to the Qinghai-Tibet Plateau. Several geographically isolated pig populations are distributed throughout the Plateau. It remained an open question if these populations have experienced different demographic histories and have evolved independent adaptive loci for the harsh environment of the Plateau. To address these questions, we herein investigated ~ 40,000 genetic variants across the pig genome in a broad panel of 678 individuals from 5 Tibetan geographic populations and 34 lowland breeds.

Results: Using a series of population genetic analyses, we show that Tibetan pig populations have marked genetic differentiations. Tibetan pigs appear to be 3 independent populations corresponding to the Tibetan, Gansu and Sichuan & Yunnan locations. Each population is more genetically similar to its geographic neighbors than to any of the other Tibetan populations. By applying a locus-specific branch length test, we identified both population-specific and -shared candidate genes under selection in Tibetan pigs. These genes, such as PLA2G12A, RGCC, C9ORF3, GRIN2B, GRID1 and EPAS1, are involved in high-altitude physiology including angiogenesis, pulmonary hypertension, oxygen intake, defense response and erythropoiesis. A majority of these genes have not been implicated in previous studies of highlanders and high-altitude animals.

Conclusion: Tibetan pig populations have experienced substantial genetic differentiation. Historically, Tibetan pigs likely had admixture with neighboring lowland breeds. During the long history of colonization in the Plateau, Tibetan pigs have developed a complex biological adaptation mechanism that could be different from that of Tibetans and other animals. Different Tibetan pig populations appear to have both distinct and convergent adaptive loci for the harsh environment of the Plateau.

Figure 1

Map of sample locations in the present study. Our samples were collected from 5 Tibetan pig geographic populations and 25 Chinese lowland breeds. Populations tested in this study are highlighted in pink. Our previously reported and online available breeds are indicated in blue and green, respectively. Phenotypes of the 5 Tibetan pig geographic populations are shown in the left panel. BAM, Bamei; BMX, Bama Xiang; CJX, Congjiang Xiang; DHB, Dahuabai; DN, Diannanxiaoer; DS, Dongshan; EHL, Erhualian; GST, Tibetan (Gansu); GX, Ganxi; HT, Hetaodaer; JH, Jinhua; JQH, Jiangquhai; KL, Kele; LIC, Lichahei; LWU, Laiwu; LUC, Luchuan; MG, Mingguangxiaoer; MIN, Min; MS, Meishan; NJ, Neijiang; RC, Rongchang; SCT, Tibetan (Sichuan); SUT, Sutai; SZL, Shaziling; TC, Tongcheng; TT1, Tibetan (Gongbujiangda); TT2, Tibetan (Milin); WB, Chinese wild boars; WZS, Wuzhishan; YNT, Tibetan (Yunnan).

Figure 2

Population split and historical mixture for Tibetan pigs in a context of Chinese diverse breeds. Arrows indicate migration events among Chinese indigenous breeds. A spectrum of heat colors indicates different migration weights at the migration event.

Figure 3

LSBL analysis identifies candidate loci under selection for high-altitude adaptation in Tibetan pigs. (A) Histograms of distribution of locus-specific branch length (LSBL) values in each and all Tibetan populations are depicted. LSBL values are shown in the x-axis and the number of individuals in the y-axis. Dashed grey lines indicate the significant thresholds: 0.5% of the empirical distribution. (B) Venn diagram shows shared and distinct candidate genes under selection in three Tibetan pig populations from Gansu, Tibet and Sichuan & Yunnan provinces. Numbers indicating how many outlier SNPs belong to each of Tibetan populations are shown in the panel.

Figure 4

Genomic signatures of selection in each and all Tibetan pig populations. (A) Genome-wide distribution of LSBL values. From top to bottom panels, LSBL outliers are shown for each Tibetan pig population from Gansu, Tibet and Sichuan & Yunnan (SCYN) provinces as well as all Tibetan pigs. The chromosomes are plotted along the x-axis, and LSBL values are plotted along the y-axis. Chromosomes are indicated by different colors, and the threshold indicating signature of selection is denoted with a dashed grey line. The strongest candidate genes corresponding to the top SNP outliers are indicated by red arrows in each panel, and the gene names are labeled above the arrows. Two flanking genes (HFM1 and ZNF644) are shown for one intergenic SNP. (B) A heat map of allele frequencies at the top SNP loci for each and overall of the tested populations. A spectrum of heat map colors indicates different allele frequencies at these loci.

Figure 5

Comparison of our highlighted candidate genes with previous reports. A venn diagram showing shared and distinct candidate genes for high-altitude adaptation between our findings, the 247 previously reported hypoxia genes [14] and 215 positively selected genes (PSGs) recently identified in the Tibetan wild boars [20].