Genome-wide Detection Of Selective Signals For High-altitude Adaptation In Tibetan Pigs By Porcine60K Chip Data

The Tibetan big, known as Tibetan snow dolphin, is one of domestic animalsindigenous to the Qing-Tibet Plateau. Because geography is steep and environment is poorin the Qing-Tibet, for example, low-oxygen, high ultra-violent radiation and lowtemperature, the Tibetan pig live in the Qing-Tibet Plateau and need some traits in responseto high-altitude environments, such as adapting reduced oxygen, resisting highultra-violent radiation and diseases, alertness and agility. Those traits have attracted manyresearchers to study. Although more and more articles has reported the molecular geneticbasis of the Tibetan pigs with different characteristics, the Qinghai-Tibet Plateau stretchesacross a vast region, the molecular mechanism of Tibetan pig`s traits is complex. More andmore basis need us to explore.We herein investigated~40,000genetic variants across the pig genome on abroadpanel of598individuals from5Tibetan geographic populations,28lowland breeds andretrieved SNP date of85pigs from6breeds from the Dryad Digital Repository. Using aseries of population genetic analyses, we show marked genetic differentiations in the5Tibetan pig populations, which appear to be3independent populations corresponding tothe Tibetan (TT), Gansu (GST) and Sichuan&Yunnan (SCYN) locations. By applyinga locus-specific branch length test and using the top0.5%of empirical distribution, wefurther identified both population-specific and–shared candidate genes under selection inTibetan pigs. The population-specific genes of selection in Gansu, Tibet and SCYNpopulations apparently correspond to96,98and96. C9ORF3, GRIN2B, and GRID1, threefunctionally plausible genes, exhibit the most significant signals of in Gansu, Tibet andSCYN population, respectively. These genes are involved in several biological processes,such as detection of mechanical stimulus, very-low-density lipoprotein particle assembly,cardiac muscle tissue morphogenesis, nicotine addiction, sulfur metabolism and DNAreplication. Population-shared genes in all Tibetan pigs correspond to89. HFM1, ZNF644,PLA2G12A, and RGCC are the most significant signals. Their biological processes areinvolved in the regulation of behavioral defense respond, fatty acid catabolism,angiogenesis, DNA biosynthetic process, apoptosis, epithelial to mesenchyme transition,glyoxylate and dicarboxylate metabolism, melanoma and fat digestion and absorption.Many genes are functionally related to high-altitude, such as resisting hypoxia,disease and high ultra-violent radiation and quickly response. These genes are first reported.So our finding provides novel insights into understanding of the genetic basis ofhigh-altitude adaptation in Tibetan pigs.Because of low genomic coverage of the60k chip, some gene is not detected. Torecruit the limitation of60k chip, we choose some genes that have been identified as targets of selection for high-altitude adaption in Tibetan and Yak. For example, EGLN1andEPAS1, two critical regulation in the HIF(hypoxia-inducible factor) pathway, have beenrepeatedly identified as targets of selection for high-altitude adaptation in Tibetans.ADAM17is the most prominent locus showing signal of positive selection in the Tibetanyak. We, therefore, are interested in whether any of the three genes has experiencedconvergent selection in Tibetan pigs. As no SNP on the current porcine60K chip is locatedaround the three genomic region, we sequentially genotyped56SNPs at an average densityof1SNP/5.4kb covering the three genes on a panel of324individuals including84Tibetan pigs and240lowland animals. The resulting genotype dates were merged into the60K SNP dataset. We then performed the LSBL analysis on the324individuals using acommon subset of informative SNPs. No significant selection signal was detected at bothEGLN1and ADAM17loci. Two of22SNPs around the EPAS1gene stand out to bepopulation-shared outliers surpassing the significance threshold. The two SNPs showapparently different variation patterns between Tibetan pigs and low-altitude individual. SoEPAS1has been selected in Tibetan pigs and played a role in high-altitude adaption.In conclusion, different Tibetan pig populations appear to have both distinct andconvergent adaptive loci for the harsh environment of Plateau. The Tibetan pigs havedeveloped a different biological adaption mechanism as compared to Tibetans and otheranimals in the Plateau, Our finding improve our understanding of the genetic basis ofhigh-altitude adaptation in Tibetan pigs. Tibetan pigs have been considered an importantpattern of humans’ animals. The study provides the molecular basis in mental diseases andbreath failure and so on.