# Analysis of Migration and Adaptive Evolution in Tibetan Sheep Populations

## TL;DR

This study explores how Tibetan sheep adapted to extreme high-altitude environments on the Qinghai–Tibet Plateau by analyzing their genomes and identifying genes linked to hypoxia, UV resistance, and water homeostasis.

## Contribution

The study identifies specific genes and pathways in Tibetan sheep associated with adaptation to hypoxia, UV radiation, and arid conditions, revealing distinct genomic signatures across different plateau regions.

## Key findings

- Five genes (HIF1AN, HBE1, HBE2, TNFAIP3, RAD50) are linked to hypoxia and UV adaptation in high-altitude Tibetan sheep.
- Genes like TP53, ATG101, and KRT80 are associated with energy, water homeostasis, and hair development in cold and arid regions.
- Tibetan sheep show stronger adaptive selection for energy and water use in arid deserts, with HIF-1 signaling countering oxidative stress.

## Abstract

The environmental conditions on the Qinghai–Tibet Plateau vary widely, ranging from the warm and humid grassland climate at mid-altitudes in the northeast to the cold, arid, and desertified climate at high altitudes in the central and western regions. However, previous genomic studies on high-altitude adaptation have primarily focused on comparisons between mid-to-high altitudes and low altitudes, neglecting the complexity of conditions within the plateau itself. Investigating the mechanisms of adaptation to different high-altitude environments will enhance our understanding of how species adapt to the extreme conditions of the plateau.

The genetic basis for Tibetan sheep adaptation to different high-altitude environments remains unknown. This study conducted whole-genome resequencing on 80 Tibetan sheep individuals from four major distribution areas on the Qinghai–Tibet Plateau. Based on the high-quality single-nucleotide polymorphisms (SNPs) obtained, an analysis of population-level genomic selection signals was performed. Population genomic analysis revealed that Tibetan sheep distributed across China originated in northern China but showed evidence of gene flow from South Asian sheep. Between populations from extremely high-altitude and mid-altitude regions, selection analyses identified five strongly positive selected genes (HIF1AN [Hypoxia Inducible Factor 1 Alpha Subunit Inhibitor], HBE1 [Hemoglobin Subunit Epsilon 1], HBE2 [Hemoglobin Subunit Epsilon 2], TNFAIP3 [TNF Alpha Induced Protein 3], RAD50 [RAD50 Double Strand Break Repair Protein]). These genes are associated with adaptation to hypoxia and intense UV radiation in high-altitude environments. Selection analyses between populations from extremely high-altitude and mid-altitude regions identified five strongly selected genes (HIF1AN [Hypoxia Inducible Factor 1 Alpha Subunit Inhibitor], HBE1 [Hemoglobin Subunit Epsilon 1], HBE2 [Hemoglobin Subunit Epsilon 2], TNFAIP3 [TNF Alpha Induced Protein 3], RAD50 [RAD50 Double Strand Break Repair Protein]) associated with hypoxia and intense UV radiation in high-altitude environments. Comparative genomic analyses of populations in cold and arid environments identified several candidate genes related to energy and water homeostasis, as well as hair development (TP53 [Tumor Protein P53], ATG101 [Autophagy Related 101], ATP12A [ATPase H+/K+ Transporting Non-Gastric Alpha2 Subunit], KRT80 [Keratin 80], KRT7 [Keratin 7]). Additionally, Tibetan sheep in the high-altitude arid deserts exhibit stronger adaptive selection for energy homeostasis and water utilization; meanwhile, the HIF-1 [Hypoxia Inducible Factor 1] signaling pathway helps counteract oxidative stress induced by extreme water scarcity in the plateau environment. Our study supports the hypothesis that Tibetan sheep originated in northern China and identifies distinct adaptive features in the Tibetan sheep genome corresponding to their habitats.